Biology subjects

Kaplan, R.

Publications and source records attributed to Kaplan, R..

26 records · Page 2Linked to original sources

bioRxiv2019

Multiple Drug Resistance in the canine hookworm Ancylostoma caninum: an Emerging Threat

In the past few years, diagnoses by veterinarians of recurrent canine hookworm infections have dramatically increased, suggesting that anthelmintic resistance (AR) may have evolved in the parasite Ancylostoma caninum. To investigate this, we established three \"suspected-resistant\" and two susceptible A. caninum isolates in research dogs for further study. The egg hatch assay (EHA) and the larval development assay (LDA) were used for detecting resistance to benzimidazoles, and macrocyclic lactones, respectively. Resistance ratios ranged from 6.0 to >100 and 5.5-69.8 for the EHA and LDA, respectively. Following treatments with fenbendazole, pyrantel and milbemycin oxime, reduction in faecal egg counts ranged from 64-86%, 0-72% and 58-92%, respectively. Deep amplicon sequencing of the isotype-1 {beta} tubulin gene identified a high frequency of resistance-associated single nucleotide polymorphisms at codon 167 in the resistant isolates and clinical cases.. These data conclusively demonstrate multiple anthelmintic resistance in A. caninum, and provide pivotal evidence that this is an emerging problem in the United States. Consequently, these findings should provide some concern to the global health community, as the scale-up of mass drug administration for soil-transmitted helminths (STH) is now placing similar selection pressures for benzimidazole resistance in human hookworms.

zoology↗

bioRxiv2019

Evidence for the F200Y (TAC) mutation conferring benzimidazole resistance in a southern USA cattle population of Haemonchus placei spreading from a single emergence

The benzimidazoles are one of the most important broad-spectrum anthelmintic drug classes for the control of parasitic nematodes of domestic animals and humans. They have been widely used in the livestock sector, particularly in small ruminants for over 40 years. This has resulted in the development and wide spread of resistance in small ruminant gastrointestinal nematode parasite species, including Haemonchus contortus. Recently, resistance to benzimidazole drugs has been reported in Haemonchus placei, but there is relatively little information on its prevalence. It is important to develop a molecular tools to identify resistance mutations in H. placei early in their development in order to understand the emergence and spread. Our previous study demonstrated the F200Y (TAC) mutation at their early stage in 6/9 H. placei populations derived from southern USA, albeit at low frequencies between 2 and 10%. The present study analysis the phylogenetics of the isotype-1 {beta}-tubulin locus to suggest that F200Y (TAC) mutation has been spread from a single emergence in H. placei; likely by the anthroprogenic movement of ruminant livestock in southern USA. Population genetic data of H. placei using a panel of microsatellite markers revealed little genetic sub-structure, consistent with a high level of gene flow in this region. Overall, these results provide clear genetic evidence for the spread of F200Y (TAC) benzimidazoles resistance mutation to multiple different locations from a single emergence in H. placei.

molecular biology↗

bioRxiv2019

Isolation and characterization of live yeast cells from ancient vessels as a tool in bio-archeology

Ancient fermented food has been studied based on recipes, residue analysis and ancient-DNA techniques and reconstructed using modern domesticated yeast. Here, we present a novel approach. We hypothesize that enriched yeast populations in fermented beverages could have become the dominant species in storage vessels and the descendants of these yeast could be isolated and studied long after. To this end, using a pipeline of yeast isolation from clay vessels developed here, we screened for yeast cells in beverage-related and non-related ancient vessels and sediments, from several archeological sites. We found that yeast cells could be successfully isolated specifically from clay containers of fermented beverages. Genomic analysis revealed that these yeast are similar to those found in traditional African beverages. Phenotypically, they grow similar to modern-beer producing yeast. Both strongly suggesting that they are descendants of the original fermenting yeast. These findings provide modern microorganisms as a new tool in bio-archeology. ImportanceSo far, most of the study of ancient organisms was based mainly on the analysis of ancient DNA. Here we show that it is possible to isolate and study microorganisms, yeast in this case, from thousands of years old clay vessels, used for fermentation. We demonstrate that it is highly likely that these cells are descendants of the original yeast strains which participated in the fermentation process and were absorbed into the pottery vessels. Moreover, we characterize the isolated yeast their genome and the beer they produce. These results open new and exciting avenues in the study of domesticated microorganisms and contribute significantly to the fields of bio and experimental -archeology that aims to reconstruct ancient artifacts and products.

ecology↗

bioRxiv2018

Hippocampal-entorhinal transformations in abstract frames of reference

Knowing how anothers preferences relate to our own is a central aspect of everyday decision-making, yet how the brain performs this transformation is unclear. Here, we ask whether the putative role of the hippocampal-entorhinal system in transforming relative and absolute spatial coordinates during navigation extends to transformations in abstract decision spaces. During fMRI scanning, subjects learned a strangers preference for an everyday activity - relative to one of three personally known individuals - and subsequently decided how the strangers preference relates to the other two individuals preferences. We found that entorhinal cortex/subiculum signals exhibited reference frame-sensitive responses to the absolute distance between the ratings of the stranger and the familiar choice options. In contrast, striatal signals increased when accurately determining the ordinal position of choice options in relation to the stranger. Paralleling its role in navigation, these data implicate the entorhinal/subicular region in assimilating relatively coded knowledge within abstract metric spaces.

neuroscience↗

bioRxiv2018

Human hippocampal theta oscillations reflect sequential dependencies during spatial planning.

Movement-related theta oscillations in rodent hippocampus coordinate forward sweeps of location-specific neural activity that could be used to evaluate spatial trajectories online. This raises the possibility that increases in human hippocampal theta power accompany the evaluation of upcoming spatial choices. To test this hypothesis, we measured neural oscillations during a spatial planning task that closely resembles a perceptual decision-making paradigm. In this task, participants searched visually for the shortest path between a start and goal location in novel mazes that contained multiple choice points, and were subsequently asked to make a spatial decision at one of those choice points. We observed ~4-8 Hz hippocampal/medial temporal lobe theta power increases specific to sequential planning that were negatively correlated with subsequent decision speed, where decision speed was inversely correlated with choice accuracy. These results implicate the hippocampal theta rhythm in decision tree search during planning in novel environments.

neuroscience↗

bioRxiv2018

Rapid Whole Genome Sequencing Decreases Morbidity and Healthcare Cost of Hospitalized Infants

BACKGROUNDGenetic disorders are a leading cause of morbidity and mortality in infants. Rapid Whole Genome Sequencing (rWGS) can diagnose genetic disorders in time to change acute medical or surgical management (clinical utility) and improve outcomes in acutely ill infants.\n\nMETHODSRetrospective cohort study of acutely ill inpatient infants in a regional childrens hospital from July 2016-March 2017. Forty-two families received rWGS for etiologic diagnosis of genetic disorders. Probands received standard genetic testing as clinically indicated. Primary end-points were rate of diagnosis, clinical utility, and healthcare utilization. The latter was modelled in six infants by comparing actual utilization with matched historical controls and/or counterfactual utilization had rWGS been performed at different time points.\n\nFINDINGSThe diagnostic sensitivity was 43% (eighteen of 42 infants) for rWGS and 10% (four of 42 infants) for standard of care (P=.0005). The rate of clinical utility for rWGS (31%, thirteen of 42 infants) was significantly greater than for standard of care (2%, one of 42; P=.0015). Eleven (26%) infants with diagnostic rWGS avoided morbidity, one had 43% reduction in likelihood of mortality, and one started palliative care. In six of the eleven infants, the changes in management reduced inpatient cost by $800, 000 to $2,000,000.\n\nDISCUSSIONThese findings replicate a prior study of the clinical utility of rWGS in acutely ill inpatient infants, and demonstrate improved outcomes and net healthcare savings. rWGS merits consideration as a first tier test in this setting.

clinical trials↗

bioRxiv2017

Planning and navigation as active inference

This paper introduces an active inference formulation of planning and navigation. It illustrates how the exploitation-exploration dilemma is dissolved by acting to minimise uncertainty (i.e., expected surprise or free energy). We use simulations of a maze problem to illustrate how agents can solve quite complicated problems using context sensitive prior preferences to form subgoals. Our focus is on how epistemic behaviour - driven by novelty and the imperative to reduce uncertainty about the world - contextualises pragmatic or goal-directed behaviour. Using simulations, we illustrate the underlying process theory with synthetic behavioural and electrophysiological responses during exploration of a maze and subsequent navigation to a target location. An interesting phenomenon that emerged from the simulations was a putative distinction between place cells - that fire when a subgoal is reached - and path cells - that fire until a subgoal is reached.

neuroscience↗

bioRxiv2017

Neurohormonal signalling controls insulin sensitivity and specificity in C. elegans

Insulin and insulin-like growth factor signalling regulates a broad spectrum of growth and metabolic responses to a variety of internal and environmental stimuli. Such responses can be tailored to the environment so that changes in insulin signalling result in distinct physiological responses to different stimuli. For example, the inhibition of insulin-like signalling by osmotic stress or by starvation of C. elegans results in physiologically distinct states and patterns of gene expression. How does insulin-like signalling elicit different responses to different environmental stimuli? We report that neurohormonal signalling involving the C. elegans cytosolic sulfotransferase SSU-1 controls developmental arrest in response to osmotic stress but not to starvation; that SSU-1 functions in a single pair of sensory neurons to control signalling via the nuclear hormone receptor NHR-1; that signalling controlled by SSU-1 acts antagonistically to insulin-like signalling; and that the FOXO transcription factor DAF-16, a downstream effector of insulin-like signalling, enters the nucleus in response to osmotic stress but activates gene expression only if SSU-1 is active. We propose that neurohormonal signalling controlled by one or more cytosolic sulfotransferases similarly regulates the specificity of responses to changes in insulin signalling during periods of environmental stress in other organisms and that abnormalities in such sulfotransferase-controlled neurohormonal signalling might contribute to human disorders that involve insulin signalling, such as obesity and type 2 diabetes.

genetics↗