The ataxic mutant mouse stargazer is a null mutant for stargazin, a protein involved in the regulation of cell surface trafficking and synaptic targeting of AMPA receptors. The extreme C terminus of stargazin (sequence, ؊TTPV), confers high affinity for PDZ domain-containing proteins e.g. PSD-95. Interaction with PDZ proteins enables stargazin to fulfill its role as an AMPA receptor synaptic targeting molecule but is not essential for its ability to influence AMPA receptor trafficking to the neuronal cell surface. Using the yeast-two hybrid approach we screened for proteins that interact with the intracellular C-terminal tail of stargazin. Positive interactors included PDZ domain-containing proteins e.g. SAP97, SAP102, and PIST. Interestingly, light chain 2 of microtubule-associated protein 1 (LC2), which does not contain a PDZ domain, was also a strong interactor. This was shown to be a direct interaction that occurred upstream of the -TTPV sequence of stargazin. Immunoprecipitations of Triton X-100 soluble cerebellar extracts revealed that LC2 is pulled down not only by anti-stargazin antibodies but also anti-GluR2 antibodies suggesting that stargazin and AMPA receptor subunits associate with LC2. Immunopurified full-length, native stargazin was shown to co-associate not only with GluR2 in vivo but also with full-length, native LC2. Indeed, LC2 co-associates with stargazin when part of a tripartite complex comprising LC2-stargazin-GluR2. Since this complex was extracted using Triton X-100 and was devoid of PSD95, SAP97, and actin we postulate that LC2 is involved in trafficking of AMPA receptors in cerebellar neurons before they are anchored at the synapse.The ataxic and epileptic mutant mouse, stargazer (stg), arose spontaneously as a consequence of a viral insertion of a 6-kb early transposon in intron 2 of the stargazin gene (1, 2). The mutation results in premature transcriptional arrest and complete ablation of stargazin expression (3, 4). From P14 onwards stg display phenotypic consequences of the mutation that includes head tossing due to an inner ear defect (2), ataxia and impaired conditioned eyeblink reflex, both a consequence of cerebellar defects (5) and absence epilepsy (6). The molecular basis for these disparate defects has still to be unequivocally resolved but ultimately these must be direct or downstream consequences of ablated expression of stargazin. Based on low sequence homology to the skeletal muscle-specific L-type voltage-gated calcium channel (VGCC) 1 ␥ 1 subunit, stargazin was proposed to be a brain-specific ␥ isoform, and in this context was named CACN␥ 2 (2). Heterologous co-expression studies showed that stargazin had relatively minor effects on P/Q-, Land ␣1L T-type VGCC kinetics and cell surface trafficking (2, 7, 8, 9, 10). It has recently been shown that the N-type VGCC ␣1B subunit co-precipitates with immunoprecipitated stargazin from detergent soluble mouse brain (4). Cerebellar GABA A receptor expression is also severely compromised in stargazer mice (11,12). The apparent f...
PurposeWe sought to understand patients’ care-seeking behaviours early in the pandemic, their use and views of different virtual care modalities, and whether these differed by sociodemographic factors.MethodsWe conducted a multisite cross-sectional patient experience survey at 13 academic primary care teaching practices between May and June 2020. An anonymised link to an electronic survey was sent to a subset of patients with a valid email address on file; sampling was based on birth month. For each question, the proportion of respondents who selected each response was calculated, followed by a comparison by sociodemographic characteristics using χ2 tests.ResultsIn total, 7532 participants responded to the survey. Most received care from their primary care clinic during the pandemic (67.7%, 5068/7482), the majority via phone (82.5%, 4195/5086). Among those who received care, 30.53% (1509/4943) stated that they delayed seeking care because of the pandemic. Most participants reported a high degree of comfort with phone (92.4%, 3824/4139), video (95.2%, 238/250) and email or messaging (91.3%, 794/870). However, those reporting difficulty making ends meet, poor or fair health and arriving in Canada in the last 10 years reported lower levels of comfort with virtual care and fewer wanted their practice to continue offering virtual options after the pandemic.ConclusionsOur study suggests that newcomers, people living with a lower income and those reporting poor or fair health have a stronger preference and comfort for in-person primary care. Further research should explore potential barriers to virtual care and how these could be addressed.
Purpose: We sought to understand patients care-seeking behaviours during the pandemic, their use and views of different virtual care modalities, and whether these differed by sociodemographic factors. Methods: We conducted a multi-site cross-sectional patient experience survey at thirteen academic primary care teaching practices between May and June of 2020. An anonymized link to an electronic survey was sent to a subset of patients with a valid email address on file; sampling was based on birth month. For each question, the proportion of respondents who selected each response was calculated, followed by a comparison by sociodemographic characteristics using chi-squared tests. Results: In total, 7482 participants responded to the survey. Most received care from their primary care clinic during the pandemic (67.7%, 5068/7482), the majority via phone (82.5%, 4195/5086). Among those who received care, 30.53% (1509/4943) stated that they delayed seeking care because of the pandemic. Most participants reported a high degree of comfort with phone (92.4%, 3824/4139), video (95.2%, 238/250) and email or messaging (91.3%, 794/870). However, those reporting difficulty making ends meet, poor or fair health, and arriving in Canada in the last 10 years reported lower levels of comfort with virtual care and fewer wanted their practice to continue offering virtual options after the pandemic. Conclusions: Our study suggest that newcomers, people living with a lower income, and those reporting poor or fair health have a stronger preference and comfort for in-person primary care. Further research should explore potential barriers to virtual care and how these could be addressed.
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