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Smith, W.

Publications and source records attributed to Smith, W..

23 records · Page 2Linked to original sources

Left/right asymmetry disruptions and mirror-image reversals to behavior andbrain anatomy in Ciona

BackgroundLeft-right asymmetries are a common feature of metazoan nervous systems. This is particularly pronounced in the comparatively simple larval central nervous system (CNS) of the tunicate Ciona, whose swimming tadpole larva shows a clear chordate ground plan. While common pathway elements for specifying the left-right axis are found in the chordates, particularly a requirement for Nodal signaling, Ciona differs from its vertebrate cousins by specifying its axis at the neurula stage, rather than at gastrula. Additionally, Ciona, and other ascidians, have a requirement for an intact chorionic membrane for proper left/right specification. ResultsWe present here results showing that left-right asymmetry disruptions caused by removal of the chorion (dechorionation) are highly variable and present throughout the Ciona larval nervous system. While previous studies have documented disruptions to the conspicuously asymmetric sensory systems in the anterior brain vesicle, we document asymmetries in seemingly symmetric structures such as the posterior brain vesicle and motor ganglion. Moreover, defects caused by dechorionation include misplaced or absent neuron classes, loss of asymmetric gene expression, aberrant synaptic connectivity, and abnormal behaviors. In the motor ganglion, a brain structure that has been equated with the vertebrate hindbrain, we find that despite the apparent left/right symmetric distribution of interneurons and motor neurons, AMPA receptors are expressed exclusively on the left side, which equates with asymmetric swimming behaviors. We also find that within a population of dechorionated larvae, there is a small percentage with apparently normal left-right specification, and approximately equal population with inverted (mirror-image) asymmetry. We present a method based on a behavioral assay for isolating these larvae. When these two classes of larvae (normal and inverted) are assessed in a light dimming assay they display mirror-image behaviors, with normal larvae responding with counterclockwise swims, while inverted larvae respond with clockwise swims. ConclusionsOur findings highlight the importance of left-right specification pathways not only for proper CNS anatomy, but also for correct synaptic connectivity and behavior.

developmental biology↗

A pilot study of behavioral, environmental, and occupational risk factors for chronic kidney disease of unknown etiology in Sri Lanka

Chronic kidney disease of unknown etiology (CKDu) was first recognized in Sri Lanka in the early 1990s, and since then it has reached epidemic levels in the North Central Province of the country. The prevalence of CKDu is reportedly highest among communities that engage in chena and paddy farming, which is most often practiced in the dry zone including the North Central and East Central Provinces of Sri Lanka. Previous studies have suggested varied hypotheses for the etiology of CKDu; however, there is not yet a consensus on the primary risk factors, possibly due to disparate study designs, sample populations, and methodologies. The goal of this pilot case-control study was to evaluate the relationships between key demographic, cultural, and occupational variables as risk factors for CKDu, with a primary interest in pesticide exposure both occupationally and through its potential use as an ingredient in brewed kasippu alcohol. A total of 56 CKDu cases and 54 control individuals were surveyed using a proctored, self-reported questionnaire. Occupational pesticide exposure and alcohol consumption were not found to be significant risk factors for CKDu. However, a statistically significant association with CKDu was observed with chewing betel (OR: 6.11, 95% CI: 1.93, 19.35), age (OR: 1.07, 95% CI: 1.02, 1.13), owning a pet dog (OR: 3.74, 95% CI: 1.38, 10.11), water treatment (OR: 3.68, 95% CI: 1.09, 12.43) and pests in the house (OR: 5.81, 95% CI: 1.56, 21.60). The findings of this study suggest future research should focus on practices associated with chewing betel, potential animal interactions including pests in the home and pets, and risk factors associated with water. AUTHOR SUMMARYSince a new variant of chronic kidney disease was acknowledged in the early 1990s among those in the agricultural community of Sri Lanka, especially rice farmers, the research community has searched for causes of what has become known as chronic kidney disease of unknown etiology or CKDu. Previous studies have focused on heavy metals in the environment as they are known to be toxic to the kidneys however, a proverbial "smoking gun" has yet to be identified. Understanding that the causes is potential multifactorial we implemented a pilot case-control study using a One Health methodology administering a comprehensive interview to assess environmental, animal, and, human exposures that may be contributing to the diagnosis of CKDu. We found statistically significant odds ratio among those that reported having a pet dog, chewing betel (a traditional preparation or various ingredients wrapped in a betel leaf inserted between the teeth and cheek), pests in the home, treating drinking water, and older age. These results serve to guide further hypothesis generation regarding mechanisms behind associated exposures from infectious diseases such as hantavirus and leptospirosis to food preparation through boiling drinking water in aluminum vessels and oral pesticide exposure linked to betel preparation.

scientific communication and education↗

Invasion but not hybridisation is associated with ecological niche shift in monkeyflowers

BackgroundThe ecological niche occupied by novel hybrids can influence their establishment as well as the potential to coexist with their parents. Hybridisation generates new phenotypic combinations, which, in some cases, may allow them to occupy ecological niches outside the environmental envelope of parental taxa. In other cases, hybrids may retain similar ecological niches to their parents, resulting in competition and affecting their coexistence. To date, few studies have quantitatively assessed niche shifts associated with hybridisation in recently introduced populations while simultaneously characterising the niche of parental species in both native and introduced ranges.\n\nAimsIn this study, we compared the ecological niche of a novel hybrid plant with the niches of its two parental taxa in the non-native geographic range. We also characterised and compared the parental taxas ecological niche of native and introduced populations in order to assess potential niche changes during the invasion process independent of hybridisation.\n\nMethodsWe studied monkeyflowers (Mimulus spp., Phrymaceae) that were introduced from the Americas to Europe and New Zealand in the last 200 years. We focused on a novel hybrid, triploid, asexual taxon (M. x robertsii) that occurs only in the British Isles where its two parents (M. guttatus and M. luteus) come into secondary contact. We assembled more than 12,000 geo-referenced occurrence records and eight environmental variables of the three taxa across native and introduced ranges, and conducted ecological niche model analysis using maximum entropy, principal component and niche dynamics analysis.\n\nResultsWe found no evidence of niche shift in the hybrid, M. x robertsii compared to introduced populations of both of their parental taxa. The hybrid had a niche more similar to M. luteus, which is also the rarest of the parental taxa on the introduced range. Among parental monkeyflowers, M. guttatus showed niche conservatism in introduced populations in Europe, but a niche shift in New Zealand, while M. luteus showed a niche shift in Europe. However, the evidence of niche shift should be treated with caution due to the occurence of non-analog climatic conditions, small population size and unfilling niche dynamics.\n\nConclusionsOur results suggest that hybridisation in non-native monkyeflowers did not result in a shift in ecological niche. This niche conservation could create competition between parental and derived taxa, the outcome of which will depend on relative competitive abilities. Further work is needed to establish if the expansion of the hybrid in the introduced range is causally related to the apparent rarity of one of the parents (M.luteus). Finally, the comparison of native and non-native populations of parental taxa, suggest that whether invasions result in niche shifts or not depends on both taxon and geographic region, highlighting the idiosyncratic nature of biological invasions.

ecology↗

Group B meningococcal outer membrane protein vaccine promote potent anti-viral effect

This report demonstrates a novel method to explore and evaluate the specific humoral/cellular immune response levels and immunoprotective effects of NMB0315 nucleic acid vaccine, recombinant protein vaccine and nucleic acid vaccine + recombinant protein vaccine in combination with mice, and to further explore the effective immunization method for NMB0315 vaccine. This route provides experimental basis. Nucleic acid vaccines [pcDNA3 1(+) / NMB0315] and recombinant protein vaccines (pET 30a / NMB0315) were prepared in large quantities, and immunologically or separately immunized female BALB/c mice were determined by nucleic acid priming protein boosting method. The specific humoral/cell immune response level, the in vitro bactericidal titer of immune serum, and the immunoprotective effect of the vaccine on mice infected with group B meningococcus were observed. Serum-specific IgG, IgG1, IgG2a and genital lavage fluids induced by NMB0315 nucleic acid vaccine group (pNMB0315 CpG), protein vaccine group (rNMB0315 FA) and combined immunization group (pNMB0315 CpG+rNMB0315 FA). The specific sIgA level reached the peak in the eighth week, and the A450 values were in vitro, and the in vitro bactericidal antibody titers of the nucleic acid vaccine group, the protein vaccine group and the combined immunization group were 1, 64, 1128, respectively. The immune protection rate of experimental mice were 70%, 95% and 80%, respectively. At 2, 4, 6, and 8 weeks, the ratio of IgG2a / IgG1 in the nucleic acid vaccine group, the recombinant protein vaccine group, and the combined immunization vaccine group was less than 1.

pharmacology and toxicology↗

Parallel Visual Circuitry in a Basal Chordate

A common CNS architecture is observed in all chordates, from vertebrates to basal chordates like the ascidian Ciona. Currently Ciona stands apart among chordates in having a complete larval CNS connectome. Starting with visuomotor circuits predicted by the Ciona connectome, we used expression maps of neurotransmitter use with behavioral assays and pharmacology to identify two parallel visuomotor circuits that are responsive to different components of visual stimuli. The first circuit is characterized by glutamatergic photoreceptors and responds to the direction of light. These photoreceptors project to cholinergic motor neurons, via two tiers of cholinergic interneurons. The second circuit is responsive to changes in ambient light and mediates an escape response. This circuit starts with novel GABAergic photoreceptors which project to GABAergic interneurons, and then to cholinergic interneurons shared with the first circuit. Our observations on neurotransmitter use and the behavior of larvae lacking photoreceptors indicate the second circuit is disinhibitory.

neuroscience↗