Mapping neural circuits across defined synapses is essential for understanding brain function. Here we describe trans-Tango, a technique for anterograde transsynaptic circuit tracing and ...manipulation. At the core of trans-Tango is a synthetic signaling pathway that is introduced into all neurons in the animal. This pathway converts receptor activation at the cell surface into reporter expression through site-specific proteolysis. Specific labeling is achieved by presenting a tethered ligand at the synapses of genetically defined neurons, thereby activating the pathway in their postsynaptic partners and providing genetic access to these neurons. We first validated trans-Tango in the Drosophila olfactory system and then implemented it in the gustatory system, where projections beyond the first-order receptor neurons are not fully characterized. We identified putative second-order neurons within the sweet circuit that include projection neurons targeting known neuromodulation centers in the brain. These experiments establish trans-Tango as a flexible platform for transsynaptic circuit analysis.
•A genetic approach for transsynaptic tracing and manipulation of neural circuits•Genetic access to neurons based on their connectivity•Glomerulus-specific patterns of second-order neurons in the fly olfactory system•Identifying second-order gustatory neurons and their target areas in the fly brain
Talay and Richman et al. develop a genetic method for transsynaptic labeling of neural circuits in Drosophila. They validate it in the olfactory system and implement it in the gustatory system to reveal second-order projections of sweet tastant-responsive neurons.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Sweet and bitter compounds excite different sensory cells and drive opposing behaviors. However, it remains unclear how sweet and bitter tastes are represented by the neural circuits linking ...sensation to behavior. To investigate this question in Drosophila, we devised trans-Tango(activity), a strategy for calcium imaging of second-order gustatory projection neurons based on trans-Tango, a genetic transsynaptic tracing technique. We found spatial overlap between the projection neuron populations activated by sweet and bitter tastants. The spatial representation of bitter tastants in the projection neurons was consistent, while that of sweet tastants was heterogeneous. Furthermore, we discovered that bitter tastants evoke responses in the gustatory receptor neurons and projection neurons upon both stimulus onset and offset and that bitter offset and sweet onset excite overlapping second-order projections. These findings demonstrate an unexpected complexity in the representation of sweet and bitter tastants by second-order neurons of the gustatory circuit.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Materials informatics (MI) has immense potential to accelerate the pace of innovation and new product development in biotechnology. Close collaborations between skilled physical and life scientists ...with data scientists are being established in pursuit of leveraging MI tools in automation and artificial intelligence (AI) to predict material properties
in vitro
and
in vivo
. However, the scarcity of large, standardized, and labeled materials data for connecting structure-function relationships represents one of the largest hurdles to overcome. In this Highlight, focus is brought to emerging developments in polymer-based therapeutic delivery platforms, where teams generate large experimental datasets around specific therapeutics and successfully establish a design-to-deployment cycle of specialized nanocarriers. Three select collaborations demonstrate how custom-built polymers protect and deliver small molecules, nucleic acids, and proteins, representing ideal use-cases for machine learning to understand how molecular-level interactions impact drug stabilization and release. We conclude with our perspectives on how MI innovations in automation efficiencies and digitalization of data-coupled with fundamental insight and creativity from the polymer science community-can accelerate translation of more gene therapies into lifesaving medicines.
Materials informatics (MI) has immense potential to accelerate the pace of innovation and new product development for polymer-based therapeutic delivery platforms in biotechnology.
Sprague-Dawley pregnant rats received a liquid ethanol diet that was nutritionally balanced and provided 35% of calories in ethanol, beginning on day 6 of gestation. Control animals were pair-fed the ...same diet except that maltose-dextrins were substituted for ethanol. At birth pups of both ethanol-exposed and pair-fed groups were fostered by surrogate mothers which received normal rat chow ad libitum. An average of eight alcohol-exposed and eight pair-fed pups were killed at 0-1, 5, 7, 10, 14, 21, 28, and 42 days. Their fixed cerebella were bisected in the midvermal plane and one-half embedded in Araldite. Thin sections were cut from lobules II/III and stained with uranyl acetate and lead citrate and visualized with the electron microscope to evaluate the effect of ethanol on Purkinje cell growth and maturation. Although the basic layering of the cerebellar cortex was not altered, alignment of Purkinje neurons to form a monocellular layer was delayed associated with disorientation of some neurons in the ethanol-exposed pups. Delayed differentiation of Purkinje neurons in the experimental animals was also noted as evidenced by the ribosomal accumulation at the basal aspect of the cell at 14 days postnatally, resembling a 7-day control pup. Purkinje neurons of control pups were well differentiated at 14/21 days, with a centralized nucleus surrounded by a cytoplasm containing Nissl bodies, numerous Golgi complexes, and mitochondria. The ethanol-exposed pups at 14/21 days showed delayed maturation indicated by a basal ribosomal mass, with few segments of rough endoplasmic reticulum. At 28/42 days the Purkinje neurons of the controls showed a greater degree of differentiation and maturation in contrast to the reduced protein-synthesizing machinery, i.e., poorly developed endoplasmic reticulum and Nissl bodies, in the experimental pups. These studies showed delayed differentiation and maturation of Purkinje neurons as a consequence of ethanol exposure.
Pregnant rats of Sprague-Dawley strain were offered a protein- and vitamin-enriched nutritionally balanced liquid ethanol diet, providing 35% of calories as ethanol. Control animals were pair-fed ...identical liquid diet except that maltose-dextrins were substituted for ethanol. Pups of both ethanol-exposed and pair-fed groups were surrogate-fostered by mothers which received normal rat chow ad libitum. An average of eight pups of each experimental and control group was killed at 0-1, 5, 7, 10, 14, 21, 28, and 42 days. After fixation, their cerebella were bisected in the midvermal plane and one-half embedded in Araldite. Thin sections cut from lobules II/III were stained with uranyl acetate and lead citrate and the synaptology of the Purkinje neurons was studied with the electron microscope in both the experimental and control groups. Impaired climbing fiber maturation was seen in ethanol-exposed pups as evident from the presence of somatic spines--climbing fiber synapses at 14 days postnatally. In the 14-day-old control pups the climbing fiber maturation was complete or nearly complete as evident by their synapses on spines situated on the smooth dendritic branches and by the absence or paucity of climbing fiber--somatic spine synapse. In addition, a reduction in the number of parallel fibers was evident from the increase in Purkinje cell spines per varicosity in the ethanol-exposed pups. We conclude, therefore, a direct or indirect effect of ethanol occurs on climbing fiber maturation and Purkinje cell parallel fiber relationship.
Abstract Objectives The prevalence and characteristics of fetal alcohol syndrome (FAS) and partial fetal alcohol syndrome (PFAS) were determined in a third primary school cohort in a community in ...South Africa (SA). Methods An active case ascertainment, two-tier screening methodology, and the revised Institute of Medicine diagnostic criteria were employed among 818 first grade pupils. Characteristics of children with FAS and PFAS are contrasted with a randomly selected control group. Data were collected and analyzed for children in the study regarding: (1) physical growth and development, including dysmorphology, (2) intelligence and behavioral characteristics, and (3) their mother's social, behavioral, and physical characteristics. Results The rate of FAS and PFAS in this area continues as the highest reported in any overall community and is much higher than rates elsewhere. In this cohort it is 68.0–89.2 per 1000. Severe episodic drinking on weekends among mothers of children with FAS and PFAS accounts for 96% of all alcohol consumed. Various measures of maternal drinking are significantly correlated with negative outcomes of children in the areas of non-verbal intelligence (−0.26), verbal intelligence (−0.28), problem behavior (0.31), and overall dysmorphology score (0.59). Significantly more FAS and PFAS exists among children of rural residents (OR = 3.79). Conclusions A high rate of FAS and PFAS was again documented in this community, and it has increased. Given population similarities, we suspect that other communities in the Western Cape Province of South Africa also have high rates. Programs for prevention are needed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Many online sources of gene interaction networks supply rich visual data regarding gene pathways that can aid in the study of biological processes, disease research and drug discovery. PathGen ...incorporates data from several sources to create transitive connections that span multiple gene interaction databases. Results are displayed in a comprehensible graphical format, showing gene interaction type and strength, database source and microarray expression data. These features make PathGen a valuable tool for in silico discovery of novel gene interaction pathways, which can be experimentally tested and verified. The usefulness of PathGen interaction analyses was validated using genes connected to the altered facial development related to Down syndrome. Availability: http://dna.cs.byu.edu/pathgen Contact: clement@cs.byu.edu Supplementary Information: Supplementary data are available at Bioinformatics online. Further information is available at http://dna.cs.byu.edu/pathgen/PathGenSupplemental.pdf
The aim of the study was to determine the prevalence and characteristics of fetal alcohol syndrome (FAS) in a second primary school cohort in a community in South Africa.
Active case ascertainment, ...two-tier screening, and Institute of Medicine assessment methodology were employed among 857 first grade pupils, most born in 1993. Characteristics of children with FAS were contrasted with characteristics of a randomly selected control group from the same classrooms. Physical growth and development, dysmorphology and psychological characteristics of the children and measures of maternal alcohol use and smoking were analyzed.
The rate of FAS found in this study is the highest yet reported in any overall community in the world, 65.2-74.2 per 1,000 children in the first grade population. These rates are 33-148 times greater than U.S. estimates and higher than in a previous cohort study in this same community (40.5-46.4 per 1,000). Detailed documentation of physical features indicates that FAS children in South Africa have characteristics similar to those elsewhere: poor growth and development, facial and limb dysmorphology, and lower intellectual functioning. Frequent, severe episodic drinking of beer and wine is common among mothers and fathers of FAS children. Their lives are characterized by serious familial, social and economic challenges, compared with controls. Heavy episodic maternal drinking is significantly associated with negative outcomes of children in the area of nonverbal intelligence but even more so in verbal intelligence, behavior and overall dysmorphology (physical anomalies). Significantly more FAS exists among children of women who were rural residents (odds ratio: 7.36, 95% confidence interval: 3.31-16.52), usually among workers on local farms.
A high rate of FAS was documented in this community. Given social and economic similarities and racial admixture, we suspect that other communities in the Western Cape have rates that also are quite high.
USGS iCoast -- did the coast change? Liu, Sophia B.; Poore, Barbara S.; Snell, Richard J. ...
Proceedings of the companion publication of the 17th ACM conference on Computer supported cooperative work & social computing,
02/2014
Conference Proceeding
"iCoast -- Did the Coast Change?" is a U.S. Geological Survey (USGS) research project that integrates crowdsourcing and citizen science techniques to develop a web application that allows interested ...volunteers to tag USGS oblique aerial photographs with qualitative information about the geomorphological changes to the coastline after Hurricane Sandy. iCoast has been collaboratively designed with coastal scientists to ensure that the crowdsourced data produced from iCoast can be used to help validate USGS predictive models of coastal change and to educate the public about coastal erosion after extreme storms. Different mechanisms for interacting with different crowds have been strategically implemented. Various sociotechnical challenges and unexpected outcomes have emerged.
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