A Single Dopamine Pathway Underlies Progressive Locomotor Deficits in a Drosophila Model of Parkinson Disease

Expression of the human Parkinson-disease-associated protein α-synuclein in all Drosophila neurons induces progressive locomotor deficits. Here, we identify a group of 15 dopaminergic neurons per hemisphere in the anterior medial region of the brain whose disruption correlates with climbing impairments in this model. These neurons selectively innervate the horizontal β and β′ lobes of the mushroom bodies, and their connections to the Kenyon cells are markedly reduced when they express α-synuclein. Using selective mushroom body drivers, we show that blocking or overstimulating neuronal activity in the β′ lobe, but not the β or γ lobes, significantly inhibits negative geotaxis behavior. This suggests that modulation of the mushroom body β′ lobes by this dopaminergic pathway is specifically required for an efficient control of startle-induced locomotion in flies

Multiscale topology classifies cells in subcellular spatial transcriptomics.

Spatial transcriptomics measures in situ gene expression at millions of locations within a tissue1, hitherto with some trade-off between transcriptome depth, spatial resolution and sample size2. Although integration of image-based segmentation has enabled impactful work in this context, it is limited by imaging quality and tissue heterogeneity. By contrast, recent array-based technologies offer the ability to measure the entire transcriptome at subcellular resolution across large samples3-6. Presently, there exist no approaches for cell type identification that directly leverage this information to annotate individual cells. Here we propose a multiscale approach to automatically classify cell types at this subcellular level, using both transcriptomic information and spatial context. We showcase this on both targeted and whole-transcriptome spatial platforms, improving cell classification and morphology for human kidney tissue and pinpointing individual sparsely distributed renal mouse immune cells without reliance on image data. By integrating these predictions into a topological pipeline based on multiparameter persistent homology7-9, we identify cell spatial relationships characteristic of a mouse model of lupus nephritis, which we validate experimentally by immunofluorescence. The proposed framework readily generalizes to new platforms, providing a comprehensive pipeline bridging different levels of biological organization from genes through to tissues

Prevalence, overlap, and predictors of functional somatic syndromes in a student sample

Background Although at least 20 different functional somatic syndromes (FSS) have been described, and overlaps between individual FSS and a high comorbidity with depressive and anxiety disorders have been suggested, barely any studies have examined a broad array of FSS within one study. Moreover, information on psychosocial risk factors gained from prospective studies is scarce. Purpose This study aimed to determine prevalence rates, overlap, and comorbidity in 17 FSS and to estimate the influence of psychosocial risk factors on the development of FSS. Methods In total, 3,054 students (73.4 % women) completed a Web survey containing questions on FSS, comorbidity, and psychosocial risk factors at baseline. Of these, 429 completed the survey again 6 months later. Results The prevalence of any FSS was 9.5 %, with 227 (78.6 %) subjects fulfilling criteria for only one FSS, 49 (17.0 %) reporting two, and 12 (4.2 %) reporting three syndromes simultaneously. Only one person suffered from four FSS at the same time. “Major depressive syndrome” (15.6 %), “panic syndrome” (4.8 %), and “other anxiety syndromes” (19.7 %) frequently occurred among persons with FSS. Significant predictors of FSS were number of somatic symptoms (OR = 1.15), impairment in daily activities (OR = 3.17), depression (OR = 1.13), and somatization (OR = 1.15). Conclusions Our findings indicate that FSS are common in nonclinical samples. The frequency of overlap and comorbidity in FSS was lower compared with previous research. A consideration of psychosocial risk factors is warranted in the prevention and management of FSS