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34 result(s) for "Vacek, David"
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Single-cell transcriptomes of developing and adult olfactory receptor neurons in Drosophila
Recognition of environmental cues is essential for the survival of all organisms. Transcriptional changes occur to enable the generation and function of the neural circuits underlying sensory perception. To gain insight into these changes, we generated single-cell transcriptomes of Drosophila olfactory- (ORNs), thermo-, and hygro-sensory neurons at an early developmental and adult stage using single-cell and single-nucleus RNA sequencing. We discovered that ORNs maintain expression of the same olfactory receptors across development. Using receptor expression and computational approaches, we matched transcriptomic clusters corresponding to anatomically and physiologically defined neuron types across multiple developmental stages. We found that cell-type-specific transcriptomes partly reflected axon trajectory choices in development and sensory modality in adults. We uncovered stage-specific genes that could regulate the wiring and sensory responses of distinct ORN types. Collectively, our data reveal transcriptomic features of sensory neuron biology and provide a resource for future studies of their development and physiology.
Relief of post-stroke spasticity with acute vibrotactile stimulation: controlled crossover study of muscle and skin stimulus methods
Background: Prior work suggests that vibratory stimulation can reduce spasticity and hypertonia.It is unknown which of three predominant approaches (stimulation of the spastic muscle, antagonist muscle, or cutaneous regions) most reduces these symptoms.Objective: Determine which vibrotactile stimulation approach is most effective at reducing spastic hypertonia among post-stroke patients.Methods: Sham-controlled crossover study with random assignment of condition order in fourteen patients with post-stroke hand spasticity. All patients were studied in four conditions over four visits: three stimulation conditions and a sham control. The primary outcome measure was the Modified Ashworth Scale, and the secondary outcome measure was the Modified Tardieu Scale measured manually and using 3D motion capture. For each condition, measures of spastic hypertonia were taken at four time points: baseline, during stimulation, after stimulation was removed, and after a gripping exercise.Results: A clinically meaningful difference in spastic hypertonia was found during and after cutaneous stimulation of the hand. Modified Ashworth and Modified Tardieu scores were reduced by a median of 1.1 (SD = 0.84, p=0.001) and 0.75 (SD = 0.65, p=0.003), respectively, during cutaneous stimulation, and by 1.25 (SD = 0.94, p=0.001) and 0.71 (SD = 0.67, p=0.003), respectively, at 15 minutes after cutaneous stimulation. Symptom reductions with spastic muscle stimulation and antagonist muscle stimulation were non-zero but not significant. There was no change with sham stimulation.Conclusions: Cutaneous vibrotactile stimulation of the hand provides significant reductions in spastic hypertonia, compared to muscle stimulation.1 Seim et al.
Temporal evolution of single-cell transcriptomes of Drosophila olfactory projection neurons
Neurons undergo substantial morphological and functional changes during development to form precise synaptic connections and acquire specific physiological properties. What are the underlying transcriptomic bases? Here, we obtained the single-cell transcriptomes of Drosophila olfactory projection neurons (PNs) at four developmental stages. We decoded the identity of 21 transcriptomic clusters corresponding to 20 PN types and developed methods to match transcriptomic clusters representing the same PN type across development. We discovered that PN transcriptomes reflect unique biological processes unfolding at each stage—neurite growth and pruning during metamorphosis at an early pupal stage; peaked transcriptomic diversity during olfactory circuit assembly at mid-pupal stages; and neuronal signaling in adults. At early developmental stages, PN types with adjacent birth order share similar transcriptomes. Together, our work reveals principles of cellular diversity during brain development and provides a resource for future studies of neural development in PNs and other neuronal types.
Between-Tactor Display Using Dynamic Tactile Stimuli
Display of illusory vibration locations between physical vibrotactile motors (tactors) placed on the skin has the potential to reduce the number of tactors in distributed tactile displays. This paper presents a between-tactor display method that uses dynamic tactile stimuli to generate illusory vibration locations. A belt with only 6 vibration motors displays 24 targets consisting of on-tactor and between-tactor locations. On-tactor locations are represented by simply vibrating the relevant single tactor. Between-tactor locations are displayed by adjusting the relative vibration amplitudes of two adjacent motors, with either (1) constant vibration amplitudes or (2) perturbed vibration amplitudes (creating local illusory motion). User testing showed that perturbations improve recognition accuracy for in-between tactor localization.
Temporal evolution of single-cell transcriptomes of Drosophila olfactory projection neurons
Abstract Neurons undergo substantial morphological and functional changes during development to form precise synaptic connections and acquire specific physiological features. What are the underlying transcriptomic bases? Here, we obtained the single-cell transcriptomes of Drosophila olfactory projection neurons (PNs) at four developmental stages. We decoded the identity of 21 transcriptomic clusters corresponding to 20 PN types and developed methods to match transcriptomic clusters representing the same PN type across development. We discovered that PN transcriptomes reflect unique biological processes unfolding at each stage—neurite growth and pruning during metamorphosis at an early pupal stage; peaked transcriptomic diversity during olfactory circuit assembly at mid-pupal stages; and neuronal signaling in adults. At early developmental stages, PN types with adjacent birth order share similar transcriptomes. Together, our work reveals principles of cellular diversity during brain development and provides a resource for future studies of neural development in PNs and other neuronal types. Competing Interest Statement The authors have declared no competing interest.
Single-cell transcriptomes of developing and adult olfactory receptor neurons in Drosophila
Abstract Recognition of environmental cues is essential for the survival of all organisms. Precise transcriptional changes occur to enable the generation and function of the neural circuits underlying sensory perception. To gain insight into these changes, we generated single-cell transcriptomes of Drosophila olfactory receptor neurons (ORNs), thermosensory and hygrosensory neurons from the third antennal segment at an early developmental and adult stage. We discovered that ORNs maintain expression of the same olfactory receptors across development. Using these receptors and computational approaches, we matched transcriptomic clusters corresponding to anatomically and physiologically defined neuronal types across multiple developmental stages. Cell-type-specific transcriptomes, in part, reflected axon trajectory choices in early development and sensory modality in adults. Our analysis also uncovered type-specific and broadly expressed genes that could modulate adult sensory responses. Collectively, our data reveal important transcriptomic features of sensory neuron biology and provides a resource for future studies of their development and physiology. Competing Interest Statement The authors have declared no competing interest. Footnotes * ↵9 co-first authors
Coordinating Receptor Expression and Wiring Specificity in Olfactory Receptor Neurons
The ultimate function of a neuron is determined by both its physiology and connectivity, but the transcriptional regulatory mechanisms that coordinate these two features are not well understood1-4. The Drosophila olfactory receptor neurons (ORNs) provide an excellent system to investigate this question. As in mammals5, each Drosophila ORN class is defined by the expression of a single olfactory receptor or a unique combination thereof, which determines their odor responses, and by the single glomerulus to which their axons target, which determines how sensory signals are represented in the brain6-10. In mammals, the coordination of olfactory receptor expression and wiring specificity is accomplished in part by olfactory receptors themselves regulating ORN wiring specificity11-13. However, Drosophila olfactory receptors do not instruct axon targeting6, 14, raising the question as to how receptor expression and wiring specificity are coordinated. Using single-cell RNA-sequencing and genetic analysis, we identified 33 transcriptomic clusters for fly ORNs. We unambiguously mapped 17 to glomerular classes, demonstrating that transcriptomic clusters correspond well with anatomically and physiologically defined ORN classes. We found that each ORN expresses ~150 transcription factors (TFs), and identified a master TF that regulates both olfactory receptor expression and wiring specificity. A second TF plays distinct roles, regulating only receptor expression in one class and only wiring in another. Thus, fly ORNs utilize diverse transcriptional strategies to coordinate physiology and connectivity.
Effect of aerobic exercise on amyloid accumulation in preclinical Alzheimer’s: A 1-year randomized controlled trial
Our goal was to investigate the role of physical exercise to protect brain health as we age, including the potential to mitigate Alzheimer's-related pathology. We assessed the effect of 52 weeks of a supervised aerobic exercise program on amyloid accumulation, cognitive performance, and brain volume in cognitively normal older adults with elevated and sub-threshold levels of cerebral amyloid as measured by amyloid PET imaging. This 52-week randomized controlled trial compared the effects of 150 minutes per week of aerobic exercise vs. education control intervention. A total of 117 underactive older adults (mean age 72.9 [7.7]) without evidence of cognitive impairment, with elevated (n = 79) or subthreshold (n = 38) levels of cerebral amyloid were randomized, and 110 participants completed the study. Exercise was conducted with supervision and monitoring by trained exercise specialists. We conducted 18F-AV45 PET imaging of cerebral amyloid and anatomical MRI for whole brain and hippocampal volume at baseline and Week 52 follow-up to index brain health. Neuropsychological tests were conducted at baseline, Week 26, and Week 52 to assess executive function, verbal memory, and visuospatial cognitive domains. Cardiorespiratory fitness testing was performed at baseline and Week 52 to assess response to exercise. The aerobic exercise group significantly improved cardiorespiratory fitness (11% vs. 1% in the control group) but there were no differences in change measures of amyloid, brain volume, or cognitive performance compared to control. Aerobic exercise was not associated with reduced amyloid accumulation in cognitively normal older adults with cerebral amyloid. In spite of strong systemic cardiorespiratory effects of the intervention, the observed lack of cognitive or brain structure benefits suggests brain benefits of exercise reported in other studies are likely to be related to non-amyloid effects. NCT02000583; ClinicalTrials.gov.
Windbreak Efficiency in Agricultural Landscape of the Central Europe: Multiple Approaches to Wind Erosion Control
Windbreak is one of the key factors for making the agriculture systems successful through reduced wind erosion, improved microclimate, increased biodiversity, and production potentiality of timber and agricultural crops. Even though windbreak occupies only a small part of agricultural landscape, its advantages on the ecological and economical perspective are quite high. This study evaluated the effects of three windbreak types on the wind erosion control in relation to their structural diversities, wind-speed reduction, and optical porosities in the central part of the Czech Republic. Diversity in the windbreak was evaluated based on its species diversity, vertical structure, spatial pattern, and complexities. Wind speed was measured at the different distances on the leeward side of the windbreak and one station placed on the windward side as a control. Windbreak characteristics were described by terrestrial photogrammetry method using the values of optical porosity. The timber volume of the windbreaks with rich biodiversity species ranged from 224 to 443 m3 ha−1height of the windbreak on the. Results of the windbreak efficiency showed significantly closer relationship between optical porosity and structural indices. The optical porosity significantly correlated with wind-speed reduction, especially in the lower part of the windbreak. A significant dependency of the windbreak efficiency on the tree dominant height was also observed for each windbreak type. The most significant effect on the wind-speed reduction in terms of structural indices had total diversity index and Arten-profile index describing vertical structures, which are recommended together with the optical porosity to evaluate the windbreak efficiency in controlling wind erosion.
The Oxymonad Genome Displays Canonical Eukaryotic Complexity in the Absence of a Mitochondrion
The discovery that the protist Monocercomonoides exilis completely lacks mitochondria demonstrates that these organelles are not absolutely essential to eukaryotic cells. However, the degree to which the metabolism and cellular systems of this organism have adapted to the loss of mitochondria is unknown. Here, we report an extensive analysis of the M. exilis genome to address this question. Unexpectedly, we find that M. exilis genome structure and content is similar in complexity to other eukaryotes and less “reduced” than genomes of some other protists from the Metamonada group to which it belongs. Furthermore, the predicted cytoskeletal systems, the organization of endomembrane systems, and biosynthetic pathways also display canonical eukaryotic complexity. The only apparent preadaptation that permitted the loss of mitochondria was the acquisition of the SUF system for Fe–S cluster assembly and the loss of glycine cleavage system. Changes in other systems, including in amino acid metabolism and oxidative stress response, were coincident with the loss of mitochondria but are likely adaptations to the microaerophilic and endobiotic niche rather than the mitochondrial loss per se. Apart from the lack of mitochondria and peroxisomes, we show that M. exilis is a fully elaborated eukaryotic cell that is a promising model system in which eukaryotic cell biology can be investigated in the absence of mitochondria.