Journals
2025 EN
Moore Geromy G. · Lloyd Steven W.
ABSTRACT A previous study from this lab identified volatilized metabolites in the headspaces of four Aspergillus strains from Louisiana, revealing substrate dependent variation, as well as compounds unique to the non‐aflatoxigenic strain and one or more of the three aflatoxigenic strains. In this study, the headspaces of four strains from each of three other states (Arizona, Georgia, and Mississippi) were captured, analyzed, and compared. Headspace variation again was substrate dependent, and two of the examined non‐aflatoxigenic strains produced an abundance of unique compounds not observed in the headspaces of strains from other regions (including Louisiana). In addition, the pool of volatile organic compounds unique to non‐aflatoxigenic Aspergillus flavus strains is here expanded ( n = 11) for future testing for biocontrol‐related properties. Similarly, the pool of compounds unique to aflatoxin producing strains is expanded ( n = 15) for further exploration as infection biomarkers.
Journals
2025 EN
Li Qifei · Claes Sandra · Van Loy Tom
+3 more
ABSTRACT The human chemokine receptor 8 (CCR8) received attention as target for the treatment of various autoimmune disorders. Phenoxybenzylpiperidine analogues are known to act as CCR8 agonists, although their structure–activity relationship (SAR) has been studied to a limited extent. In this study, the SAR of phenoxybenzylpiperidinyl analogues was explored in a systematic way by fusion or insertion of various heterocyclic groups on the piperidinyl ring, yielding a set of 21 novel phenoxybenzylpiperidinyl derivatives. Evaluation of potential CCR8 agonism in a cell‐based assay revealed that the newly synthesized compounds were clearly less potent than the reference compounds, with the most potent analogues displaying an EC 50 value of 4 µM. Despite the fact that CCR8 agonism tolerated quite some structural variety on the piperidinyl moiety, this study demonstrated that the substitution pattern has some structural constraints for CCR8 agonism.
Journals
2025 EN
Marshall Andrea G. · Stephens Dominique · Neikirk Kit
+35 more
ABSTRACT Alzheimer's Disease (AD) is a global health issue, affecting over 6 million people in the United States, with that number expected to increase as the population ages. As a neurodegenerative disorder that affects memory and cognitive functions, it is well established that AD is associated with cardiovascular risk factors beyond only cerebral decline. In this study, we measured hemodynamic parameters related to cardiovascular and cerebrovascular function in 5xFAD mice with AD and their littermates. Specifically, we measured cardiovascular pulse wave velocity parameters, a marker of arterial stiffness and cardiovascular risk, and cerebrovascular pulse wave velocity, a novel technique to measure cerebral arterial stiffness. Our results showed that while 5xFAD mice exhibited significant differences in ejection time, pulse pressure, and Tei index, many other cardiovascular and cerebral parameters were not different. Despite reports that amyloid plaque deposition begins at an early age of 1.5 months in 5xFAD mice, our results did not indicate significant cardiovascular changes. Studies to elucidate cardiovascular and cerebrovascular parametric changes should be done at later ages where the underlying changes are more profound.
Journals
2025 UN
Marshall Andrea G. · Stephens Dominique · Neikirk Kit
+35 more
The cover image is based on the article Alterations in Cardiovascular Parameters in 5xFAD Murine Model by Antentor Hinton et al., https://doi.org/10.1002/cbf.70138
Journals
2025 EN
Song Zhendong · Li Yinlong · Dahl Kenneth
+18 more
Abstract The histamine subtype 3 (H 3 ) receptor is an important drug target in the central nervous system (CNS), and PET imaging offers a promising technique for the noninvasive evaluation of CNS disease related to the H 3 receptor. In this study, we synthesized and evaluated the binding effects of [ 18 F]H3–2404 and [ 18 F]H3–2405 by modifying the structure of AZD5213, a selective H 3 antagonist. These two radioligands were prepared in high radiochemical yields and displayed stability in serum. The in vitro autoradiographic study in rat brain tissue and the following in vivo PET studies in mice demonstrated sufficient brain uptake but predominantly non‐specific distribution in rodent brain. Although these data suggest that [ 18 F]H3–2404 and [ 18 F]H3–2405 are unsuitable as PET tracers for brain imaging of the H 3 receptor, this study provides a valuable attempt for optimizing 18 F labeled radiotracers based on AZD5213.
Journals
2025 EN
Sternicki Louise M. · Pukala Tara L. · Pacholarz Kamila J.
+4 more
Biotin protein ligase (BPL) catalyzes the covalent attachment of biotin onto biotin‐dependent enzymes, where it functions as an essential cofactor. Eukaryotic BPLs are distinct due to the presence of a large N‐terminal extension to the conserved catalytic domain and C‐terminal cap. No high‐resolution structures of a eukaryotic BPL have been solved; however, previous functional studies revealed the N‐terminal extension interacts with the biotinylation substrate. Mass spectrometry (MS) and complementary techniques were utilized to investigate the structure of the yeast Saccharomyces cerevisiae BPL ( Sc BPL). Lower resolution techniques suggested holo‐ Sc BPL had a more compact structure and sampled fewer conformational states. In addition, solution‐phase and a charge state dependent gas‐phase stabilization was observed. Hydrogen‐deuterium exchange (HDX) MS provided experimental validation of the AlphaFold predicted structure of Sc BPL, with a folded domain structurally homologous to a glutamine amidotransferase identified in the N‐terminal extension, and a mostly homologous catalytic domain to that of other species’ BPLs. Further HDX analyses identified localized conformational changes in the Sc BPL active site and N‐terminal domain that occur concomitantly with ligand binding. These data provide novel insights into the unique structure of a class III BPL and how ligands influence this structure for catalysis of protein biotinylation.
Journals
2025 EN
Song Zhendong · Li Yinlong · Dahl Kenneth
+18 more
The histamine subtype 3 receptor (H 3 R) is mainly expressed in the brain, where it plays a key role in various neurological functions. This brain imaging, featuring glowing neural connections, highlights the high expression of H 3 R. The molecular structure approaching the brain represents new Positron Emission Tomography (PET) probes for precise brain imaging. The light trail indicates the potential of this PET probe to visualize H 3 R, providing insights into brain function and pathology. More details can be found in Research Article 10.1002/cbic.202400655 by Magnus Schou, Steven H Liang, and co‐workers.
Journals
2025 EN
Pliakos Elina · Glassmoyer Lauren · Kobayashi Taisei
+6 more
ABSTRACT Background Pulmonary embolism is associated with a significant burden of morbidity, mortality, and health care costs. Catheter‐directed thrombolysis has emerged as a promising option for patients with intermediate‐risk pulmonary embolism which aims to improve outcomes over standard anticoagulation. Methods We constructed a decision‐analytic model comparing the cost‐effectiveness of catheter‐directed thrombolysis to anticoagulation alone for the management of intermediate‐risk pulmonary embolism. Cost‐effectiveness was determined by calculating deaths averted and incremental cost‐effectiveness ratios (ICER). Uncertainty was addressed by plotting cost‐effectiveness planes and acceptability curves for various willingness‐to‐pay thresholds. The main outcome was ICER (US dollars/deaths averted). Results In the base case analysis, derived using systemic lysis data, the cost associated with catheter‐directed thrombolysis was estimated at $22,353 with a probability of survival at 1 month of 0.984. For the anticoagulation alone strategy, the cost was $25,060, and the probability of survival at 1 month was 0.958. Overall, catheter‐directed thrombolysis resulted in savings of $104,089 per death averted (ICER,—$104,089 per death averted). Sensitivity analysis revealed that catheter‐directed thrombolysis would no longer be cost‐effective when its associated mortality is greater than 0.042. In the probabilistic analysis, at a willingness‐to‐pay of $100,000, catheter‐directed thrombolysis had a 63% chance of being cost‐effective, and in cost‐effectiveness acceptability curves, it was cost‐effective in 63%–78% of simulations for a willingness to pay ranging from $0 to $100,000. Conclusions If the assumptions made in our model are shown to be accurate then CDT would be cost‐effective and may lead to considerable cost savings if used where clinically appropriate.
Journals
2025 EN
Un KaChun · Wong ChunKa · Yong SanFui Sophia
+7 more
ABSTRACT Carcinoid heart disease is an important complication of neuroendocrine tumors that may lead to significant morbidity and mortality. Right‐sided heart valve involvement with consequent valve dysfunction is one of the common manifestations. Patients often have multiple, significant comorbidities with advanced metastatic disease and, as such, may not be suitable for surgical valve replacement due to excessive risk. Transcatheter valve replacement using balloon‐expandable valves has been the mainstay of management for these patients, particularly with stenotic lesions but there is limited experience in patients with pulmonary regurgitation and dilated pulmonary arteries outside the dimensions that would be suitable for these valves. We report three successful cases of percutaneous pulmonary valve implantation with the VenusP‐valve, a large self‐expanding valve platform, and highlight the technical aspects and challenges specific to treatment of pulmonary regurgitation in patients with carcinoid heart disease. Percutaneous pulmonary valve implantation, using the VenusP‐valve, may be considered an effective treatment in this patient group.
Journals
2025 EN
Saeed Yusef · Feroze Rafey · Frazzetto Marco
+1 more
ABSTRACT Percutaneous and surgical approaches have been developed for left atrial appendage occlusion. Residual stump formation with a depth of ≥ 10 mm is a recognized complication after surgical LAAO using AtriClip (Atricure, Mason, Ohio). The standard imaging modality for preprocedural planning and postprocedural follow up during these procedures has been transesophageal echocardiography. The current case describes successful closure of a residual stump, measuring 13 mm in depth, using percutaneous LAAO, with CT imaging utilized for preprocedural planning and postprocedural follow up. Accordingly, this case demonstrates that CT imaging is a viable, convenient, and less invasive alternative for these situations.