Since the rise of cellular organisms, transmembrane proteins (TMPs) are crucial to a variety of cellular processes due to their central role as gates and gatekeepers. Despite their importance, experimental high-resolution structures for TMPs remain underrepresented due to technical limitations. With structure prediction methods coming of age, predictions might fill some of the need. However, identifying the membrane regions and topology in three-dimensional structure files requires additional in silico prediction. Here, we introduce TMvisDB to sieve through millions of predicted structures for TMPs. This resource enables both, to browse through 46 million predicted TMPs and to visualize those along with their topological annotations. The database was created by joining AlphaFold DB structure predictions and transmembrane topology predictions from the protein language model based method TMbed. We show the utility of TMvisDB for individual proteins through two single use cases, namely the B-lymphocyte antigen CD20 (Homo sapiens) and the cellulose synthase (Novosphingobium sp. P6W). To demonstrate the value for large scale analyses, we focus on all TMPs predicted for the human proteome. TMvisDB is freely available at tmvis.predictprotein.org.
Neuronavigated repetitive transcranial magnetic stimulation (nrTMS) is an innovative technique that provides insight into language function with high accuracy in time and space. So far, nrTMS has mainly been applied in presurgical language mapping of patients with cranial neoplasms. For the present study nrTMS was used for language mapping in primary progressive aphasia Seven patients (median age: 70 years, 4 males) with the non-fluent variant of primary progressive aphasia were included in this pilot study. Inhibitory nrTMS trains (5 Hz, 40 % resting motor threshold) caused virtual lesions at 46 standardized cortical stimulation targets per hemisphere. Patients’ errors in a naming task during stimulation were counted. The majority of errors induced occurred during frontal lobe stimulation (34.3 %). Timing errors and non-responses were most frequent. More errors were induced in the right hemisphere (58%) than in the left hemisphere (42%). Mapping was tolerated by all patients, however, discomfort or pain was reported for stimulation of frontal areas. The elevated right-hemispheric error rate in our study supports the hypothesis of a partial shift of language function to the right hemisphere in neurodegenerative aphasia during the course of disease and therefore points to the existence of significant neuronal plasticity in primary progressive aphasia. While this is an interesting finding for neurodegenerative disorders per se, its promotion might also harbor future therapeutic targets.
Navigated repetitive transcranial magnetic stimulation (nrTMS) is an innovative technique that provides insight into language function with high accuracy in time and space. So far, nrTMS has mainly been applied in presurgical language mapping of patients with intracranial neoplasms. For the present study, nrTMS was used for language mapping in primary progressive aphasia (PPA). Seven patients (median age: 70 years, 4 males) with the non-fluent variant of PPA (nfvPPA) were included in this pilot study. Trains of nrTMS (5 Hz, 100% resting motor threshold) caused virtual lesions at 46 standardized cortical stimulation targets per hemisphere. Patients’ errors in a naming task during stimulation were counted. The majority of errors induced occurred during frontal lobe stimulation (34.3%). Timing errors and non-responses were most frequent. More errors were induced in the right hemisphere (58%) than in the left hemisphere (42%). Mapping was tolerated by all patients, however, discomfort or pain was reported for stimulation of frontal areas. The elevated right-hemispheric error rate in our study could be due to a partial shift of language function to the right hemisphere in neurodegenerative aphasia during the course of disease and therefore points to the existence of neuronal plasticity in nfvPPA. While this is an interesting finding for neurodegenerative disorders per se, its promotion might also harbor future therapeutic targets.
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