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Ondrechen, M. J.

Publications and source records attributed to Ondrechen, M. J..

5 recordsLinked to original sources

Virtually the same? Evaluating the effectiveness of remote undergraduate research experiences

In-person undergraduate research experiences (UREs) promote students integration into careers in life science research. In 2020, the COVID-19 pandemic prompted institutions hosting summer URE programs to offer them remotely, raising questions about whether undergraduates who participate in remote research can experience scientific integration. To address this, we investigated indicators of scientific integration for students who participated in remote life science URE programs in summer 2020. We found that these students experienced gains in their scientific self-efficacy and scientific identity similar to results reported for in-person UREs. We also found that these students perceived high benefits and low costs of doing research at the outset of their programs, and their perceptions did not change despite the remote circumstances. Yet, their perceptions differed by program, indicating that programs differentially affected students perceptions of the costs of doing research. Finally, we observed that students with prior research experience made greater gains in self-efficacy and identity, as well as in their perceptions of the alignment of their values with those of the scientific community, in comparison to students with no prior research experience. This finding suggests that additional programming may be needed for undergraduates with no prior experience to benefit from remote research.

scientific communication and education↗

Design, synthesis, and characterization of mG2P026 as a high contrast PET imaging ligand for metabotropic glutamate receptor 2

An array of triazolopyridines based on JNJ-46356479 (6) were synthesized as potential PET imaging ligands for metabotropic glutamate receptor 2 (mGluR2) in the brain. The selected candidates 8-11 featured an enhanced positive allosteric modulator (PAM) activity (37-fold max.) and an apparent mGluR2 agonist activity (25-fold max.) compared to compound 6. Radiolabeling of compounds 8 and 9 (also named mG2P026) was achieved via the Cu(I)-mediated radiofluorination in the automated TRACERLabTM FXF-N platform. Both [18F]8 and [18F]9 were obtained with satisfactory radiochemical yields (> 5%, non-decay corrected), high molar activity (> 180 GBq/mol), and excellent chemical and radiochemical purities (> 98%). Preliminary characterization of [18F]8 and [18F]9 in rats confirmed their excellent brain permeability with [18F]9 showing better brain heterogeneity and favorable binding kinetics. Pretreatment with different classes of PAMs enhanced the radioactivity uptake for both [18F]8 and [18F]9 at the regions of interest by 20.3-40.9% and 16.7-81.6%, respectively, due to their pharmacological effects. Further evaluation of [18F]9 in a nonhuman primate confirmed its superior brain heterogeneity in mapping mGlu2 receptors and its higher specific binding than [18F]6. Pretreatment with 0.5 mg/kg BINA led (2) to an enhanced brain uptake of [18F]9 by 3% in high tracer uptake regions that was consistent with the rat studies. Therefore, [18F]9 has the potential to be translated for human studies.

neuroscience↗

Synthesis and characterization of 5-(2-fluoro-4-pyridine-7-carboxamide as a PET imaging ligand for metabotropic glutamate receptor 2

Metabotropic glutamate receptor 2 (mGluR2) is a therapeutic target for the treatment of several neuropsychiatric disorders and conditions. The role of mGluR2 function in etiology could be unveiled by in vivo imaging using positron emission tomography (PET). In this regard, 5-(2- fluoro-4-[11C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridine-7- carboxamide ([11C]13), a potent negative allosteric modulator (NAM), was developed to support this endeavor. Radioligand [11C]13 was synthesized via the O-[11C]methylation of phenol 24 with a high molar activity of 212 {+/-} 76 GBq/{micro}mol (n = 5) and excellent radiochemical purity (> 99%). PET imaging of [11C]13 in rats demonstrated its superior brain heterogeneity, particularly in the regions of striatum, thalamus, hippocampus, and cortex. Accumulation of [11C]13 in these regions of interest (ROIs) was reduced with pretreatment of mGluR2 NAMs, VU6001966 (9) and MNI-137 (26), the extent of which revealed a time-dependent drug effect of the blocking agents. In a nonhuman primate, [11C]13 selectively accumulated in mGluR2-rich regions, especially in different cortical areas, putamen, thalamus, and hippocampus, and resulted in high-contrast brain images. The regional total volume of distribution (VT) estimates of [11C]13 decreased by 14% after the pretreatment with 9. Therefore, [11C]13 is a potential candidate for translational PET imaging studies of mGluR2 function.

neuroscience↗

Protein crosslinking as a therapeutic strategy for SOD1-related ALS

Mutations in the gene encoding Cu-Zn superoxide dismutase 1 (SOD1) cause a subset of familial amyotrophic lateral sclerosis (fALS). One effect of these mutations is that SOD1, which is normally a stable dimer, dissociates into toxic monomers. Considerable research efforts have been devoted to developing compounds that stabilize the dimer of fALS SOD1 variants, but these have not yet resulted in an approved drug. We demonstrate that a cyclic thiosulfinate cross-linker can stabilize prevalent disease-causing SOD1 variants. The degree of stabilization afforded by cyclic thiosulfinates (up to 24 {degrees}C) is unprecedented. We show this compound works rapidly in vivo with a half-life of ~3 days. The efficacy, low toxicity, and pharmacodynamics of cross-linker mediated stabilization make it a promising therapeutic approach for SOD1-related fALS. Significance statementCyclic thiosulfinate S-XL6 enables the kinetic stabilization of ALS-associated SOD1 variants, in vivo.

neuroscience↗

"How do we do this at a distance?!" A descriptive study of remote undergraduate research programs during COVID-19

The COVID-19 pandemic shut down undergraduate research programs across the U.S. Twenty-three sites offered remote undergraduate research programs in the life sciences during summer 2020. Given the unprecedented offering of remote research experiences, we carried out a study to describe and evaluate these programs. Using structured templates, we documented how programs were designed and implemented, including who participated. Through focus groups and surveys, we identified programmatic strengths and shortcomings as well as recommendations for improvements from the perspectives of participating students. Strengths included the quality of mentorship, opportunities for learning and professional development, and development of a sense of community. Weaknesses included limited cohort building, challenges with insufficient structure, and issues with technology. Although all programs had one or more activities related to diversity, equity, inclusion, and justice, these topics were largely absent from student reports even though programs coincided with a peak in national consciousness about racial inequities and structural racism. Our results provide evidence for designing remote REUs that are experienced favorably by students. Our results also indicate that remote REUs are sufficiently positive to further investigate their affordances and constraints, including the potential to scale up offerings, with minimal concern about disenfranchising students.

scientific communication and education↗