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Article ; Online: Development of an E. coli-based norbaeocystin production platform and evaluation of behavioral effects in rats

Alexandra M. Adams / Nicholas A. Anas / Abhishek K. Sen / Jordan D. Hinegardner-Hendricks / Philip J. O’Dell / William J. Gibbons, Jr. / Jessica E. Flower / Matthew S. McMurray / J. Andrew Jones

Metabolic Engineering Communications, Vol 14, Iss , Pp e00196- (2022)

2022

Abstract: Interest in the potential therapeutic efficacy of psilocybin and other psychedelic compounds has escalated significantly in recent years. To date, little is known regarding the biological activity of the psilocybin pathway intermediate, norbaeocystin, ... ...

Abstract	Interest in the potential therapeutic efficacy of psilocybin and other psychedelic compounds has escalated significantly in recent years. To date, little is known regarding the biological activity of the psilocybin pathway intermediate, norbaeocystin, due to limitations around sourcing the phosphorylated tryptamine metabolite for in vivo testing. To address this limitation, we first developed a novel E. coli platform for the rapid and scalable production of gram-scale amounts of norbaeocystin. Through this process we compare the genetic and fermentation optimization strategies to that of a similarly constructed and previously reported psilocybin producing strain, uncovering the need for reoptimization and balancing upon even minor genetic modifications to the production host. We then perform in vivo measurements of head twitch response to both biosynthesized psilocybin and norbaeocystin using both a cell broth and water vehicle in Long-Evans rats. The data show a dose response to psilocybin while norbaeocystin does not elicit any pharmacological response, suggesting that norbaeocystin and its metabolites may not have a strong affinity for the serotonin 2A receptor. The findings presented here provide a mechanism to source norbaeocystin for future studies to evaluate its disease efficacy in animal models, both individually and in combination with psilocybin, and support the safety of cell broth as a drug delivery vehicle.
Keywords	Norbaeocystin ; Psilocybin ; Head twitch response ; Psychedelic medicine ; Depression ; Long-Evans rat ; Biotechnology ; TP248.13-248.65 ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: An Open-Source Knowledge Graph Ecosystem for the Life Sciences

Callahan, Tiffany J. / Tripodi, Ignacio J. / Stefanski, Adrianne L. / Cappelletti, Luca / Taneja, Sanya B. / Wyrwa, Jordan M. / Casiraghi, Elena / Matentzoglu, Nicolas A. / Reese, Justin / Silverstein, Jonathan C. / Hoyt, Charles Tapley / Boyce, Richard D. / Malec, Scott A. / Unni, Deepak R. / Joachimiak, Marcin P. / Robinson, Peter N. / Mungall, Christopher J. / Cavalleri, Emanuele / Fontana, Tommaso /

Valentini, Giorgio / Mesiti, Marco / Gillenwater, Lucas A. / Santangelo, Brook / Vasilevsky, Nicole A. / Hoehndorf, Robert / Bennett, Tellen D. / Ryan, Patrick B. / Hripcsak, George / Kahn, Michael G. / Bada, Michael / Baumgartner Jr, William A. / Hunter, Lawrence E.

2023

Abstract: Translational research requires data at multiple scales of biological organization. Advancements in sequencing and multi-omics technologies have increased the availability of these data, but researchers face significant integration challenges. Knowledge ... ...

Abstract	Translational research requires data at multiple scales of biological organization. Advancements in sequencing and multi-omics technologies have increased the availability of these data, but researchers face significant integration challenges. Knowledge graphs (KGs) are used to model complex phenomena, and methods exist to construct them automatically. However, tackling complex biomedical integration problems requires flexibility in the way knowledge is modeled. Moreover, existing KG construction methods provide robust tooling at the cost of fixed or limited choices among knowledge representation models. PheKnowLator (Phenotype Knowledge Translator) is a semantic ecosystem for automating the FAIR (Findable, Accessible, Interoperable, and Reusable) construction of ontologically grounded KGs with fully customizable knowledge representation. The ecosystem includes KG construction resources (e.g., data preparation APIs), analysis tools (e.g., SPARQL endpoints and abstraction algorithms), and benchmarks (e.g., prebuilt KGs and embeddings). We evaluated the ecosystem by systematically comparing it to existing open-source KG construction methods and by analyzing its computational performance when used to construct 12 large-scale KGs. With flexible knowledge representation, PheKnowLator enables fully customizable KGs without compromising performance or usability.
Keywords	Computer Science - Artificial Intelligence ; Computer Science - Computational Engineering ; Finance ; and Science
Subject code	004
Publishing date	2023-07-11
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Warmer temperatures trigger insecticide-associated pest outbreaks.

Crossley, Michael S / Smith, Olivia M / Barman, Apurba K / Croy, Jordan R / Schmidt, Jason M / Toews, Michael D / Snyder, William E

Pest management science

2023 Volume 80, Issue 3, Page(s) 1008–1015

Abstract: Background: Rising global temperatures are associated with emerging insect pests, reflecting earlier and longer insect activity, faster development, more generations per year and changing species' ranges. Insecticides are often the first tools available ...

Abstract	Background: Rising global temperatures are associated with emerging insect pests, reflecting earlier and longer insect activity, faster development, more generations per year and changing species' ranges. Insecticides are often the first tools available to manage these new threats. In the southeastern US, sweet potato whitefly (Bemisia tabaci) has recently become the major threat to vegetable production. We used data from a multi-year, regional whitefly monitoring network to search for climate, land use, and management correlates of whitefly activity. Results: Strikingly, whiteflies were detected earlier and grew more abundant in landscapes with greater insecticide use, but only when temperatures were also relatively warm. Whitefly outbreaks in hotter conditions were not associated with specific active ingredients used to suppress whiteflies, which would be consistent with a regional disruption of biocontrol following sprays for other pests. In addition, peak whitefly detections occurred earlier in areas with more vegetable production, but later with more cotton production, consistent with whiteflies moving among crops. Conclusion: Altogether, our findings suggest possible links between warmer temperatures, more abundant pests, and frequent insecticide applications disrupting biological control, though this remains to be explicitly demonstrated. Climate-initiated pesticide treadmills of this type may become an increasingly common driver of emerging pest outbreaks as global change accelerates. © 2023 Society of Chemical Industry.
MeSH term(s)	Animals ; Insecticides ; Temperature ; Insecta ; Hemiptera ; Crops, Agricultural ; Vegetables
Chemical Substances	Insecticides
Language	English
Publishing date	2023-11-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2001705-4
ISSN	1526-4998 ; 1526-498X
ISSN (online)	1526-4998
ISSN	1526-498X
DOI	10.1002/ps.7832
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Article ; Online: CD8

Palmeri, Joseph R / Lax, Brianna M / Peters, Joshua M / Duhamel, Lauren / Stinson, Jordan A / Santollani, Luciano / Lutz, Emi A / Pinney, William / Bryson, Bryan D / Dane Wittrup, K

Nature communications

2024 Volume 15, Issue 1, Page(s) 1900

Abstract: Although co-stimulation of T cells with agonist antibodies targeting 4-1BB (CD137) improves antitumor immune responses in preclinical studies, clinical success has been limited by on-target, off-tumor activity. Here, we report the development of a tumor- ... ...

Abstract	Although co-stimulation of T cells with agonist antibodies targeting 4-1BB (CD137) improves antitumor immune responses in preclinical studies, clinical success has been limited by on-target, off-tumor activity. Here, we report the development of a tumor-anchored ɑ4-1BB agonist (ɑ4-1BB-LAIR), which consists of a ɑ4-1BB antibody fused to the collagen-binding protein LAIR. While combination treatment with an antitumor antibody (TA99) shows only modest efficacy, simultaneous depletion of CD4+ T cells boosts cure rates to over 90% of mice. Mechanistically, this synergy depends on ɑCD4 eliminating tumor draining lymph node regulatory T cells, resulting in priming and activation of CD8+ T cells which then infiltrate the tumor microenvironment. The cytotoxic program of these newly primed CD8+ T cells is then supported by the combined effect of TA99 and ɑ4-1BB-LAIR. The combination of TA99 and ɑ4-1BB-LAIR with a clinically approved ɑCTLA-4 antibody known for enhancing T cell priming results in equivalent cure rates, which validates the mechanistic principle, while the addition of ɑCTLA-4 also generates robust immunological memory against secondary tumor rechallenge. Thus, our study establishes the proof of principle for a clinically translatable cancer immunotherapy.
MeSH term(s)	Animals ; Mice ; Antibodies ; Antineoplastic Agents ; CD8-Positive T-Lymphocytes ; Immunotherapy ; Neoplasms/immunology ; Neoplasms/therapy ; Tumor Microenvironment ; T-Lymphocytes, Regulatory ; 4-1BB Ligand/immunology
Chemical Substances	Antibodies ; Antineoplastic Agents ; 4-1BB Ligand
Language	English
Publishing date	2024-03-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45625-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Book ; Online: Ontologizing Health Systems Data at Scale

Callahan, Tiffany J. / Stefanski, Adrianne L. / Wyrwa, Jordan M. / Zeng, Chenjie / Ostropolets, Anna / Banda, Juan M. / Baumgartner Jr., William A. / Boyce, Richard D. / Casiraghi, Elena / Coleman, Ben D. / Collins, Janine H. / Deakyne-Davies, Sara J. / Feinstein, James A. / Haendel, Melissa A. / Lin, Asiyah Y. / Martin, Blake / Matentzoglu, Nicolas A. / Meeker, Daniella / Reese, Justin /

Sinclair, Jessica / Taneja, Sanya B. / Trinkley, Katy E. / Vasilevsky, Nicole A. / Williams, Andrew / Zhang, Xingman A. / Denny, Joshua C. / Robinson, Peter N. / Ryan, Patrick / Hripcsak, George / Bennett, Tellen D. / Hunter, Lawrence E. / Kahn, Michael G.

Making Translational Discovery a Reality

2022

Abstract: Background: Common data models solve many challenges of standardizing electronic health record (EHR) data, but are unable to semantically integrate all the resources needed for deep phenotyping. Open Biological and Biomedical Ontology (OBO) Foundry ... ...

Abstract	Background: Common data models solve many challenges of standardizing electronic health record (EHR) data, but are unable to semantically integrate all the resources needed for deep phenotyping. Open Biological and Biomedical Ontology (OBO) Foundry ontologies provide computable representations of biological knowledge and enable the integration of heterogeneous data. However, mapping EHR data to OBO ontologies requires significant manual curation and domain expertise. Objective: We introduce OMOP2OBO, an algorithm for mapping Observational Medical Outcomes Partnership (OMOP) vocabularies to OBO ontologies. Results: Using OMOP2OBO, we produced mappings for 92,367 conditions, 8611 drug ingredients, and 10,673 measurement results, which covered 68-99% of concepts used in clinical practice when examined across 24 hospitals. When used to phenotype rare disease patients, the mappings helped systematically identify undiagnosed patients who might benefit from genetic testing. Conclusions: By aligning OMOP vocabularies to OBO ontologies our algorithm presents new opportunities to advance EHR-based deep phenotyping. Comment: Supplementary Material is included at the end of the manuscript
Keywords	Computer Science - Databases ; Computer Science - Artificial Intelligence ; J.3
Subject code	006
Publishing date	2022-09-10
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mesowestern Blot: Simultaneous Analysis of Hundreds of Submicroliter Lysates.

Zadeh, Cameron O / Huggins, Jonah R / Sarmah, Deepraj / Westbury, Baylee C / Interiano, William R / Jordan, Micah C / Phillips, S Ashley / Dodd, William B / Meredith, Wesley O / Harold, Nicholas J / Erdem, Cemal / Birtwistle, Marc R

ACS omega

2022 Volume 7, Issue 33, Page(s) 28912–28923

Abstract: Western blotting is a widely used technique for molecular-weight-resolved analysis of proteins and their posttranslational modifications, but high-throughput implementations of the standard slab gel arrangement are scarce. The previously developed ... ...

Abstract	Western blotting is a widely used technique for molecular-weight-resolved analysis of proteins and their posttranslational modifications, but high-throughput implementations of the standard slab gel arrangement are scarce. The previously developed Microwestern requires a piezoelectric pipetting instrument, which is not available for many labs. Here, we report the Mesowestern blot, which uses a 3D-printable gel casting mold to enable high-throughput Western blotting without piezoelectric pipetting and is compatible with the standard sample preparation and small (∼1 μL) sample sizes. The main tradeoffs are reduced molecular weight resolution and higher sample-to-sample CV, making it suitable for qualitative screening applications. The casted polyacrylamide gel contains 336, ∼0.5 μL micropipette-loadable sample wells arranged within a standard microplate footprint. Polyacrylamide % can be altered to change molecular weight resolution profiles. Proof-of-concept experiments using both infrared-fluorescent molecular weight protein ladder and cell lysate (RIPA buffer) demonstrate that the protein loaded in Mesowestern gels is amenable to the standard Western blotting steps. The main difference between Mesowestern and traditional Western is that semidry horizontal instead of immersed vertical gel electrophoresis is used. The linear range of detection is at least 32-fold, and at least ∼500 attomols of β-actin can be detected (∼29 ng of total protein from mammalian cell lysates: ∼100-300 cells). Because the gel mold is 3D-printable, users with access to additive manufacturing cores have significant design freedom for custom layouts. We expect that the technique could be easily adopted by any typical cell and molecular biology laboratory already performing Western blots.
Language	English
Publishing date	2022-08-11
Publishing country	United States
Document type	Journal Article
ISSN	2470-1343
ISSN (online)	2470-1343
DOI	10.1021/acsomega.2c02201
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Article ; Online: A multimodality review of male urethral imaging: pearls and pitfalls with an update on urethral stricture treatment.

Revels, Jonathan Wesley / Wang, Sherry S / Weaver, Jennifer S / Foreman, Jordan R / Gallegos, Maxx A / Thompson, William M / Katz, Douglas / Moshiri, Mariam

The British journal of radiology

2022 Volume 95, Issue 1134, Page(s) 20211034

Abstract: Optimum radiological assessment of the male urethra requires knowledge of the normal urethral anatomy and ideal imaging techniques based on the specific clinical scenario. Retrograde urethrography is the workhorse examination for male urethral imaging, ... ...

Abstract	Optimum radiological assessment of the male urethra requires knowledge of the normal urethral anatomy and ideal imaging techniques based on the specific clinical scenario. Retrograde urethrography is the workhorse examination for male urethral imaging, usually utilized as the initial, and often solitary, modality of choice not only in the setting of trauma, but also in the pre- and post-operative evaluation of urethral strictures. There is, however, growing interest in utilization of ultrasound and magnetic resonance for evaluation of the male urethra owing to lack of ionizing radiation and improved delineation of the adjacent tissue. We review the various modalities utilized for imaging of the male urethra for a variety of known or suspected disorders, and provide an update on current treatments of urethral strictures. Additionally, we detail the key information needed by urologists to guide management of urethral strictures. We conclude with a brief discussion of neophallus urethral diseases following female-to-male sexual confirmation surgery.
MeSH term(s)	Female ; Humans ; Magnetic Resonance Imaging/methods ; Male ; Radiography ; Ultrasonography ; Urethra/diagnostic imaging ; Urethral Stricture/diagnostic imaging ; Urethral Stricture/therapy
Language	English
Publishing date	2022-05-05
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2982-8
ISSN	1748-880X ; 0007-1285
ISSN (online)	1748-880X
ISSN	0007-1285
DOI	10.1259/bjr.20211034
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Article: Tregs constrain CD8

Palmeri, Joseph R / Lax, Brianna M / Peters, Joshua M / Duhamel, Lauren / Stinson, Jordan A / Santollani, Luciano / Lutz, Emi A / Pinney, William / Bryson, Bryan D / Wittrup, K Dane

bioRxiv : the preprint server for biology

2023

Abstract: Although co-stimulation of T cells with agonist antibodies targeting 4-1BB (CD137) improves antitumor immune responses in preclinical studies, clinical development has been hampered by on-target, off-tumor toxicity. Here, we report the development of a ... ...

Abstract	Although co-stimulation of T cells with agonist antibodies targeting 4-1BB (CD137) improves antitumor immune responses in preclinical studies, clinical development has been hampered by on-target, off-tumor toxicity. Here, we report the development of a tumor-anchored ɑ4-1BB agonist (ɑ4-1BB-LAIR), which consists of an ɑ4-1BB antibody fused to the collagen binding protein LAIR. While combination treatment with an antitumor antibody (TA99) displayed only modest efficacy, simultaneous depletion of CD4
Language	English
Publishing date	2023-02-01
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.01.30.526116
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Article: Use of Three-dimensional Mapping to Identify an Alternating Atrial Activation Pattern in the Coronary Sinus.

Sundaram, Sri A / Boorman, Chas D / Mullins, Nate A / Jordan, J Ryan / Choe, William C

The Journal of innovations in cardiac rhythm management

2018 Volume 9, Issue 5, Page(s) 3128–3131

Abstract: Atypical left atrial flutters present following atrial fibrillation ablation have been well-documented in the literature. These arrhythmias are known to be difficult to localize and ablate. An atypical flutter with an alternating activation pattern in ... ...

Abstract	Atypical left atrial flutters present following atrial fibrillation ablation have been well-documented in the literature. These arrhythmias are known to be difficult to localize and ablate. An atypical flutter with an alternating activation pattern in the coronary sinus, however, is unusual and has rarely been discussed. In this case report, we describe the use of high-density three-dimensional anatomic mapping to successfully localize and terminate an atypical flutter with an alternating atrial activation pattern in the coronary sinus.
Language	English
Publishing date	2018-05-15
Publishing country	United States
Document type	Case Reports
ISSN	2156-3977
ISSN	2156-3977
DOI	10.19102/icrm.2018.090504
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Outcomes in Patients With 4 to 10 Brain Metastases Treated With Dose-Adapted Single-Isocenter Multitarget Stereotactic Radiosurgery

Grace J. Kim, MD, PhD / Evan D. Buckley, MS / James E. Herndon, PhD / Karen J. Allen, NP / Tyketra S. Dale, NP / Justus D. Adamson, PhD / Lam Lay, BA / William M. Giles, PhD / Anna E. Rodrigues, PhD / Zhiheng Wang, PhD / Chris R. Kelsey, MD / Jordan A. Torok, Jr, MD / Junzo P. Chino, MD / Peter E. Fecci, MD, PhD / John H. Sampson, MD, PhD, MBA / Carey K. Anders, MD / Scott R. Floyd, MD, PhD / Fang-Fang Yin, PhD / John P. Kirkpatrick, MD, PhD

Advances in Radiation Oncology, Vol 6, Iss 6, Pp 100760- (2021)

A Prospective Study

2021

Abstract: Purpose: To examine the effectiveness and safety of single-isocenter multitarget stereotactic radiosurgery using a volume-adapted dosing strategy in patients with 4 to 10 brain metastases. Methods and Materials: Adult patients with 4 to 10 brain ... ...

Abstract	Purpose: To examine the effectiveness and safety of single-isocenter multitarget stereotactic radiosurgery using a volume-adapted dosing strategy in patients with 4 to 10 brain metastases. Methods and Materials: Adult patients with 4 to 10 brain metastases were eligible for this prospective trial. The primary endpoint was overall survival. Secondary endpoints were local recurrence, distant brain failure, neurologic death, and rate of adverse events. Exploratory objectives were neurocognition, quality of life, dosimetric data, salvage rate, and radionecrosis. Dose was prescribed in a single fraction per RTOG 90-05 or as 5 Gy × 5 fractions for lesions ≥3 cm diameter, lesions involving critical structures, or single-fraction brain V12Gy >20 mL. Results: Forty patients were treated with median age of 61 years, Karnofsky performance status 90, and 6 brain metastases. Twenty-two patients survived longer than expected from the time of protocol SRS, with 1 living patient who has not reached that milestone. Median overall survival was 8.1 months with a 1-year overall survival of 35.7%. The 1-year local recurrence rate was 5% (10 of 204 of evaluable lesions) in 12.5% (4 of 32) of the patients. Distant brain failure was observed in 19 of 32 patients with a 1-year rate of 35.8%. Grade 1-2 headache was the most common complaint, with no grade 3-5 treatment-related adverse events. Radionecrosis was observed in only 5 lesions, with a 1-year rate of 1.5%. Rate of neurologic death was 20%. Neurocognition and quality of life did not significantly change 3 months after SRS compared with pretreatment. Conclusions: These results suggest that volume-adapted dosing single-isocenter multitarget stereotactic radiosurgery is an effective and safe treatment for patients with 4 to 10 brain metastases.
Keywords	Medical physics. Medical radiology. Nuclear medicine ; R895-920 ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
Subject code	616 ; 610
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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