Biology subjects

Smith, T. A.

Publications and source records attributed to Smith, T. A..

7 recordsLinked to original sources

bioRxiv2026

Estimating mosquito bionomics parameters with a hierarchical Bayesian model

BackgroundThe malaria transmission potential and the vulnerability of Anopheles mosquitoes to different vector control methods depend, among other factors, on the endophily, endophagy, anthropophagy and survival of each species. Local information on these bionomic parameters is generally unavailable. MethodsTo address this, we estimated species-specific values of these parameters using an augmented version of the global database of bionomics data by Massey et al. (2016). We applied inclusion and exclusion criteria to select eligible studies with relevant experimental designs that minimise bias from collection methods for parous, sac, endophagy, and endophily rates as well as for the resting duration. For the human blood index (HBI), we separated data from indoor and outdoor collections. We fitted hierarchical Bayesian models with levels based on Anopheles taxonomy to estimate these quantities. Based on the estimated bionomics, we quantified the expected vectorial capacity reduction after the introduction of a pyrethroid-pyrrole insecticide-treated net (ITN) for 57 Anopheles species. ResultsWe identified 26 eligible studies for endophagy and 61 for the parous rate, leading to a Bayesian posterior average for the Anopheles genus of 42% (95% credible interval: 18-70) and 55% (32-77) respectively. HBI values widely varied depending on the location of collection, except for some species showing strong anthropophilic behaviours. Resting duration was estimated to be 2.1 days (1.2 - 4.8) at the genus level. Few studies were available to estimate the sac and endophily rates, which prevented us from deriving precise estimates for the whole Anopheles genus. Our estimates of the vectorial capacity reduction following the introduction of a pyrrole-pyrethroid ITN ranged between 48% and 76% across species, highlighting the important differences among mosquito species in vulnerability to vector control interventions. ConclusionThis work demonstrates how data from both Anopheles species complexes and individual species can be leveraged to generate species-specific estimates of bionomic parameters, capturing the local characteristics and behaviour of malaria vectors. The dataset is readily updatable as new data become available. However, more frequent and standardised field surveys are still needed to accurately characterise local vector behaviour.

zoology↗

bioRxiv2023

SPARK regulates AGC kinases central to the Toxoplasma gondii asexual cycle

Apicomplexan parasites balance proliferation, persistence, and spread in their metazoan hosts. AGC kinases, such as PKG, PKA, and the PDK1 ortholog SPARK, integrate environmental signals to toggle parasites between replicative and motile life stages. Recent studies have cataloged pathways downstream of apicomplexan PKG and PKA; however, less is known about the global integration of AGC kinase signaling cascades. Here, conditional genetics coupled to unbiased proteomics demonstrates that SPARK complexes with an elongin-like protein to regulate the stability of PKA and PKG in the model apicomplexan Toxoplasma gondii. Defects attributed to SPARK depletion develop after PKG and PKA are down-regulated. Parasites lacking SPARK differentiate into the chronic form of infection, which may arise from reduced activity of a coccidian-specific PKA ortholog. This work delineates the signaling topology of AGC kinases that together control transitions within the asexual cycle of this important family of parasites.

microbiology↗

bioRxiv2021

Testing for implicit emotion regulation in childhood

Although implicit emotion regulation is thought to be critical for psychosocial development and mental wellbeing, few studies have investigated the neural underpinnings of this form of emotion regulation in children. We used a modified emotional Go/NoGo block design fMRI task to explore the neural correlates of implicit emotion regulation and individual differences in a sample of 40 children (50% female, mean age = 8.65 {+/-} 0.77). Conditions included happy, sad, neutral, and scrambled faces as implicit distractors within the actual Go/NoGo targets. We used a relatively standard preprocessing pipeline via fMRIprep, with T-contrasts for response inhibition and emotional effects, and a nonparametric multiple comparisons procedure, with SnPM, for our group-level analysis. There were multiple significant response inhibition effects, including larger NoGo vs Go activation in the IFG, insula, and MCC/ACC. Valence effects showed significantly greater right putamen activity for the Sad NoGo vs Go contrast and greater bilateral putamen and right pallidum activity for the Happy Go vs Sad Go contrast. These results provide preliminary findings of neural substrates, particularly the putamen, that may be associated with implicit emotion regulation in children.

neuroscience↗

bioRxiv2021

High-throughput functionalization of the Toxoplasma kinome uncovers a novel regulator of invasion and egress

Protein kinases regulate fundamental aspects of cell biology in all eukaryotes, making them attractive chemotherapeutic targets in Apicomplexan parasites such as the causative agents of malaria (Plasmodium spp.) and toxoplasmosis (Toxoplasma gondii). However, the precise roles of individual parasite kinases cannot be inferred simply from sequence identity, due to rewiring of signaling pathways and the shifting repertoire of kinases across species. To systematically examine the parasite kinome, we developed a high-throughput (HiT) CRISPR-mediated tagging strategy to endogenously label all predicted cytosolic protein kinases with a synthetic sequence encoding the minimal auxin-inducible degron (mAID) linked to a fluorophore and epitope tag. The system enables the assembly of thousands of tagging vectors from synthetic sequences in a single reaction and the pooled generation of mutants to examine kinase localization and function. We examined the phenotypes associated with kinase knock-down in 1,160 arrayed clones by replica-plating in the presence or absence of auxin and found broad defects across the lytic cycle for 109 clonal isolates, assigning localizations to 39 proteins, and associating 15 kinases within 6 distinct morphological phenotypes. The relative fitness of tagged alleles was also examined by tracking the relative abundance of individual guide RNAs as parasite populations progressed through the lytic cycle, in the presence or absence of auxin. Pooled screening had a high predictive value and differentiated between delayed and acute death. Demonstrating the value of this resource, we identified a novel kinase associated with delayed death as a novel regulator of invasion and egress. We call the previously unstudied kinase Store Potentiating/Activating Regulatory Kinase (SPARK), based on its impact on intracellular Ca2+ stores at key moments during the lytic cycle. Despite having a similar kinase domain to the mammalian PDK1, SPARK lacks the canonical lipid-binding domain and we find no indication SPARK positively regulates other AGC kinases, suggesting a rewiring of signaling pathways to accommodate parasite adaptations. The HiT vector screening system extends the applications of genome-wide screens into complex cellular phenotypes, providing a scalable and versatile platform for the dissection of apicomplexan cell biology.

microbiology↗

bioRxiv2018

C. elegans germ cells divide and differentiate along a folded epithelium

Knowing how stem cells and their progeny are positioned within their tissues is essential for understanding their regulation. One paradigm for stem cell regulation is the C. elegans germline, which is maintained by a pool of germline stem cells in the distal gonad, in a region known as the progenitor zone. The C. elegans germline is widely used as a stem cell model, but the cellular architecture of the progenitor zone has been unclear. Here we characterize this architecture by creating virtual 3D models of the progenitor zone in both sexes. We show that the progenitor zone in adult hermaphrodites is essentially a folded epithelium. The progenitor zone in males is not folded. Analysis of germ cell division shows that daughter cells are born side-by-side along the surface of the epithelium. Analysis of a key regulator driving differentiation, GLD-1, shows that germ cells in hermaphrodites differentiate along the path of the folded epithelium, with previously described \"steps\" in GLD-1 expression corresponding to germline folds. Our study provides a three-dimensional view of how C. elegans germ cells progress from stem cell to overt differentiation, with critical implications for regulators driving this transition.

developmental biology↗

bioRxiv2017

Simulations for Designing and Interpreting Intervention Trials in Infectious Diseases

Here we urge the adoption of a new paradigm for the design and interpretation of intervention trials in infectious diseases, particularly in emerging infectious disease, that more accurately reflects the dynamics of the transmission process. Interventions in infectious diseases can have indirect effects on those not receiving the intervention as well as direct effects on those receiving the intervention. Combinations of interventions can have complex interactions at the population level. These often cannot be adequately addressed with standard study designs and analytic methods. Simulations can help to accurately represent transmission dynamics in an increasingly complex world which is critical for proper trial design and interpretation. Some ethical aspects of a trial can also be quantified using simulations. After a trial has been conducted, simulations can be used to explore possible explanations for the observed effects. A great deal is to be gained through a multidisciplinary approach that builds collaborations among experts in infectious disease dynamics, epidemiology, statistical science, economics, simulation methods and the conduct of clinical trials.

epidemiology↗

bioRxiv2017

The experience of vivid autobiographical reminiscence is supported by personal semantic representations in the precuneus

Recent studies have suggested that the human posteromedial cortex (PMC), which includes core regions of the default mode network (DMN), plays an important role in episodic memory. Whereas various roles relating to self-relevant processing and memory retrieval have been attributed to different subsystems within this broad network, the nature of representations and the functional roles they support in these brain regions remain unspecified. Here, we describe the whole-brain networks that represent subjective, self-relevant aspects of real-world events during autobiographical recollection. Nine participants wore a device to record images from their lives for a period of two to four weeks (lifelogging phase) and indicated the personally-salient attributes (i.e., personal semantics) of each episode by choosing multiple content tags. Two to four weeks after the lifelogging phase, participants relived their experiences in an fMRI scanner cued by images chosen from their own lives. Representational Similarity Analysis revealed a broad network, including parts of the DMN, that represented personal semantics during autobiographical reminiscence. Furthermore, within this network, the right precuneus represented personally relevant content during vivid recollection but not during non-vivid recollection. The precuneus is a hub within the DMN and has been implicated in metacognitive ability for memory retrieval. Our results suggest a more specific mechanism underlying the phenomenology of vivid reminiscence, supported by personal semantic representations in the precuneus.

neuroscience↗