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Item Freezing of Gait in Parkinson’s Disease: Invasive and Noninvasive Neuromodulation(Elsevier, 2021-07) Rahimpour, Shervin; Gaztanaga, Wendy; Yadav, Amol P.; Chang, Stephano J.; Krucoff, Max O.; Cajigas, Iahn; Turner, Dennis A.; Wang, Doris D.; Neurological Surgery, School of MedicineIntroduction: Freezing of gait (FoG) is one of the most disabling yet poorly understood symptoms of Parkinson's disease (PD). FoG is an episodic gait pattern characterized by the inability to step that occurs on initiation or turning while walking, particularly with perception of tight surroundings. This phenomenon impairs balance, increases falls, and reduces the quality of life. Materials and methods: Clinical-anatomical correlations, electrophysiology, and functional imaging have generated several mechanistic hypotheses, ranging from the most distal (abnormal central pattern generators of the spinal cord) to the most proximal (frontal executive dysfunction). Here, we review the neuroanatomy and pathophysiology of gait initiation in the context of FoG, and we discuss targets of central nervous system neuromodulation and their outcomes so far. The PubMed database was searched using these key words: neuromodulation, freezing of gait, Parkinson's disease, and gait disorders. Conclusion: Despite these investigations, the pathogenesis of this process remains poorly understood. The evidence presented in this review suggests FoG to be a heterogenous phenomenon without a single unifying pathologic target. Future studies rigorously assessing targets as well as multimodal approaches will be essential to define the next generation of therapeutic treatments.Item Genetic mapping and identification of a QTL determining tolerance to freezing stress in Fragaria vesca L(Public Library of Science, 2021-05-21) Davik, Jahn; Wilson, Robert C.; Njah, Relindis G.; Grini, Paul E.; Randall, Stephen K.; Alsheik, Muath K.; Sargent, Daniel James; Biology, School of ScienceExtreme cold and frost cause significant stress to plants which can potentially be lethal. Low temperature freezing stress can cause significant and irreversible damage to plant cells and can induce physiological and metabolic changes that impact on growth and development. Low temperatures cause physiological responses including winter dormancy and autumn cold hardening in strawberry (Fragaria) species, and some diploid F. vesca accessions have been shown to have adapted to low-temperature stresses. To study the genetics of freezing tolerance, a F. vesca mapping population of 143 seedlings segregating for differential responses to freezing stress was raised. The progeny was mapped using 'Genotyping-by-Sequencing' and a linkage map of 2,918 markers at 851 loci was resolved. The mapping population was phenotyped for freezing tolerance response under controlled and replicated laboratory conditions and subsequent quantitative trait loci analysis using interval mapping revealed a single significant quantitative trait locus on Fvb2 in the physical interval 10.6 Mb and 15.73 Mb on the F. vesca v4.0 genome sequence. This physical interval contained 896 predicted genes, several of which had putative roles associated with tolerance to abiotic stresses including freezing. Differential expression analysis of the 896 QTL-associated gene predictions in the leaves and crowns from 'Alta' and 'NCGR1363' parental genotypes revealed genotype-specific changes in transcript accumulation in response to low temperature treatment as well as expression differences between genotypes prior to treatment for many of the genes. The putative roles, and significant interparental differential expression levels of several of the genes reported here identified them as good candidates for the control of the effects of freezing tolerance at the QTL identified in this investigation and the possible role of these candidate genes in response to freezing stress is discussed.