Pavel Itskov - Academia.edu (original) (raw)

Papers by Pavel Itskov

Nature Communications, Aug 4, 2014

Frontiers Research Topics, 2014

The mechanical hand of the future will roll a screw between its fingers and sense, by touch, whic... more The mechanical hand of the future will roll a screw between its fingers and sense, by touch, which end is which. This paper describes a step toward such a manipulator-a robot finger that is used to recognize small objects by touch. The device incorporates a novel imaging tactile sensor-an artificial skin with hundreds of pressure sensors in a space the size of a finger tip. ''he sensor is mounted on a tendon-actuated mechanical finger, similar in size and range of motion to a human index finger. A program controls the finger, using it to press and probe the object placed in front of it. Based on how the object feels, the program guesses its shape and orientation and then uses the finger to test and refine the hypothesis. The device is programmed to recognize commonly used fastening devicesnuts, bolts, flat washers, lock washers, dowel pins, cotter pins, and set screws.

Cell, 2014

The global rise in obesity has revitalized a search for genetic and epigenetic factors underlying... more The global rise in obesity has revitalized a search for genetic and epigenetic factors underlying the disease. We present a Drosophila model of paternal-diet-induced intergenerational metabolic reprogramming (IGMR) and identify genes required for its encoding in offspring. Intriguingly, we find that as little as 2 days of dietary intervention in fathers elicits obesity in offspring. Paternal sugar acts as a physiological suppressor of variegation, desilencing chromatin-state-defined domains in both mature sperm and in offspring embryos. We identify requirements for H3K9/K27me3-dependent reprogramming of metabolic genes in two distinct germline and zygotic windows. Critically, we find evidence that a similar system may regulate obesity susceptibility and phenotype variation in mice and humans. The findings provide insight into the mechanisms underlying intergenerational metabolic reprogramming and carry profound implications for our understanding of phenotypic variation and evolution.

Cells, 2022

The statin drug target, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), is strongly linked to b... more The statin drug target, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), is strongly linked to body mass index (BMI), yet how HMGCR influences BMI is not understood. In mammals, studies of peripheral HMGCR have not clearly identified a role in BMI maintenance and, despite considerable central nervous system expression, a function for central HMGCR has not been determined. Similar to mammals, Hmgcr is highly expressed in the Drosophila melanogaster brain. Therefore, genetic and pharmacological studies were performed to identify how central Hmgcr regulates Drosophila energy metabolism and feeding behavior. We found that inhibiting Hmgcr, in insulin-producing cells of the Drosophila pars intercerebralis (PI), the fly hypothalamic equivalent, significantly reduces the expression of insulin-like peptides, severely decreasing insulin signaling. In fact, reducing Hmgcr expression throughout development causes decreased body size, increased lipid storage, hyperglycemia, and hyperphagia. Fu...

19 Because acoustic landscapes are complex and rapidly changing, auditory systems have evolved 20... more 19 Because acoustic landscapes are complex and rapidly changing, auditory systems have evolved 20 mechanisms that permit rapid detection of novel sounds, sound source segregation and perceptual 21 restoration of sounds obscured by noise. Perceptual restoration is particularly important in noisy 22 environments, because it allows organisms to track sounds over time even when they are masked. The 23 continuity illusion is a striking example of perceptual restoration, with sounds perceived as intact even 24 when parts of them have been replaced by gaps, and rendered inaudible by being masked by an 25 extraneous sound. The mechanisms of auditory filling-in are complex and are currently not well 26 understood. The present study used the high temporal resolution of EEG to examine brain activity related 27 to continuity illusion perception. Masking noise loudness was adjusted individually for each subject, so 28 that physically identical sounds on some trials elicited a continuity illusion...

Acta Neurobiologiae Experimentalis, 2009

A comparison of the ethograms generated by manual annotation with the results of our automated me... more A comparison of the ethograms generated by manual annotation with the results of our automated method confirmed the accuracy of our approach. The number of “sips” detected by our algorithm was strongly and significantly correlated with the number of proboscis contacts with the food (Rho=0.874, p<<0.0001). The algorithm detected 92.5% of the sips tabulated via manual scoring, while missing 7.5% and generating 7.5% false sips. We have found that feeding from a non-liquid food induces a pattern of highly stereotyped rhythmic proboscis extensions and retractions that is suggestive of an underlying central pattern generator controlling the feeding motor program. By adapting the luciferase bioluminescent techniques to measure the intake in single flies we measured that 1 "sip" detected by the flyPAD corresponds on average to an intake of 1 nl of food. The analysis of ingestion dynamics and the microstructure of meals allowed us to dissect the behavioral elements mediating ...

1.Animals need to balance competitive behaviours to maintain internal homeostasis and to reproduc... more 1.Animals need to balance competitive behaviours to maintain internal homeostasis and to reproduce. The underlying mechanisms are complex, but typically involve neuroendocrine signalling. Using Drosophila, we systematically manipulated signalling between energy-mobilising endocrine cells producing adipokinetic hormone (AKH), octopaminergic neurons and the energy-storing fat body to assess whether this neuroendocrine axis involved in starvation-induced hyperactivity also balances activity levels under ad libitum access to food.Our results suggest that AKH signals via two divergent pathways that are mutually competitive in terms of activity and rest. AKH increases activity via the octopaminergic system during the day, while it prevents high activity levels during the night by signalling to the fat body. This regulation involves feedback signalling from octopaminergic neurons to AKH-producing cells. AKH-producing cells are known to integrate a multitude of metabolic and endocrine signa...

Neuroscience & Biobehavioral Reviews

PLOS Biology

Stress responses are crucial processes that require activation of genetic programs that protect f... more Stress responses are crucial processes that require activation of genetic programs that protect from the stressor. Stress responses are also energy consuming and can thus be deleterious to the organism. The mechanisms coordinating energy consumption during stress response in multicellular organisms are not well understood. Here, we show that loss of the epigenetic regulator G9a in Drosophila causes a shift in the transcriptional and metabolic responses to oxidative stress (OS) that leads to decreased survival time upon feeding the xenobiotic paraquat. During OS exposure, G9a mutants show overactivation of stress response genes, rapid depletion of glycogen, and inability to access lipid energy stores. The OS survival deficiency of G9a mutants can be rescued by a high-sugar diet. Control flies also show improved OS survival when fed a high-sugar diet, suggesting that energy availability is generally a limiting factor for OS tolerance. Directly limiting access to glycogen stores by knocking down glycogen phosphorylase recapitulates the OS-induced survival defects of G9a mutants. We propose that G9a mutants are sensitive to stress because they experience a net reduction in available energy due to (1) rapid glycogen use, (2) an inability to access lipid energy stores, and (3) an overinduced transcriptional response to stress that further exacerbates energy demands. This suggests that G9a acts as a critical regulatory hub between the transcriptional and metabolic responses to OS. Our findings, together with recent studies that established a role for G9a in hypoxia resistance in cancer cell lines, suggest that G9a is of wide importance in controlling the cellular and organismal response to multiple types of stress.

The regulation of feeding plays a key role in determining the fitness of animals through its impa... more The regulation of feeding plays a key role in determining the fitness of animals through its impact on nutrition. Elucidating the circuit basis of feeding and related behaviors is an important goal in neuroscience. We recently used a system for closed-loop optogenetic manipulation of neurons contingent on the fly’s feeding behavior to dissect the impact of a specific subset of taste neurons on yeast feeding (Steck et al., 2018). Here we describe the development and validation of this system, which we term the optoPAD. We use the optoPAD to induce appetitive and aversive effects on feeding by activating or inhibiting gustatory neurons in closed loop – effectively creating virtual taste realities. The use of optogenetics allowed us to vary the dynamics and probability of stimulation in single flies and assess the impact on feeding behavior quantitatively and with high throughput. These data demonstrate that the optoPAD is a powerful tool to dissect the circuit basis of feeding behavio...

To optimize fitness, animals must dynamically match food choices to their current needs. For dros... more To optimize fitness, animals must dynamically match food choices to their current needs. For drosophilids, yeast fulfils most dietary protein and micronutrient requirements. While several yeast metabolites activate known gustatory receptor neurons (GRNs) in Drosophila melanogaster, the chemosensory channels mediating yeast feeding remain unknown. Here we identify a class of proboscis GRNs required for yeast intake, and show that these GRNs act redundantly to mediate yeast feeding. While nutritional and reproductive states synergistically increase yeast appetite, we find a separation of these state signals at the level of GRN responses to yeast: amino acid but not mating state enhances yeast GRN gain. The sensitivity of sweet GRNs to sugar is not increased by protein deprivation, providing a potential basis for protein-specific appetite. The emerging picture is that different internal states act at distinct levels of a dedicated gustatory circuit to elicit nutrient-specific appetites...

PLoS biology, Apr 1, 2017

Choosing the right nutrients to consume is essential to health and wellbeing across species. Howe... more Choosing the right nutrients to consume is essential to health and wellbeing across species. However, the factors that influence these decisions are poorly understood. This is particularly true for dietary proteins, which are important determinants of lifespan and reproduction. We show that in Drosophila melanogaster, essential amino acids (eAAs) and the concerted action of the commensal bacteria Acetobacter pomorum and Lactobacilli are critical modulators of food choice. Using a chemically defined diet, we show that the absence of any single eAA from the diet is sufficient to elicit specific appetites for amino acid (AA)-rich food. Furthermore, commensal bacteria buffer the animal from the lack of dietary eAAs: both increased yeast appetite and decreased reproduction induced by eAA deprivation are rescued by the presence of commensals. Surprisingly, these effects do not seem to be due to changes in AA titers, suggesting that gut bacteria act through a different mechanism to change ...

Frontiers in Behavioral Neuroscience, 2014

Active touch can be described as the control of the position and movement of tactile sensing syst... more Active touch can be described as the control of the position and movement of tactile sensing systems by reaching out and exploring-sensing by "touching" as opposed to being touched. The active nature of these movements entails precise control of the sensory apparatus, which is task-specific and maximizes sensory information from the environment. This collection brings together a group of articles from progressive, early career scientists who are researching active touch sensing from a variety of different perspectives including behavioral, physiological, neuronal, computational, and robotic. There are a host of different model systems that are used to investigate active touch sensing and this collection sees the three main systems represented; that of the human hand, mammalian whiskers, and insect antennae. In this collection we have grouped the studies together into sections by their system and each section contains a collection of articles from both Frontiers in Behavioral Neuroscience and Frontiers in Neurorobotics. We feel that this indicates the truly multidisciplinary nature of studying active touch.