Biology subjects

Sweeney, A. M.

Publications and source records attributed to Sweeney, A. M..

5 recordsLinked to original sources

bioRxiv2024

Enhancements in squid retinal responses to change of polarizations in a caustic shallow water

Marine animals with polarization vision are able to effectively detect moving objects in shallow waters, which are illuminated by dynamic fluctuations of downwelling light known as caustics. While behavioral studies across different animal species have demonstrated the support of polarization vision in moving object detection within this noisy environment, little is known about how their retinal photoreceptors, absorbing polarized photons, respond to moving objects, or how each photoreceptor contributes to the collective retinal reaction to changes in polarization. In this study, we employed multi-electrode array recordings to examine the retinal neural response of squid to polarized light stimuli that were designed to simulate caustics environment. Extracellular retinal recordings not only exhibit neural activities selective to the direction of polarization but also demonstrate a significant enhancement in response to stimuli with changing polarization compared to constant polarization. This enhancement is robust in almost all recording channels, but absent in a random permutation of the recordings from different trial types. These results suggest that the retinal photoreceptors directly encode the change of polarization stimuli, thereby contributing to signal detections with polarization vision. Together, our research represents a novel neural exploration of cephalopod polarization vision in a caustic environment, and advances our understanding of how nature parses scenes with salient, dynamic polarization in animal vision.

zoology↗

bioRxiv2024

Identification of SARS-CoV-2 Mpro inhibitors through deep reinforcement learning for de novo drug design and computational chemistry approaches

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of coronavirus disease (COVID-19) since its emergence in December 2019. As of January 2024, there has been over 774 million reported cases and 7 million deaths worldwide.[1] While vaccination efforts have been successful in reducing the severity of the disease and decreasing the transmission rate, the development of effective therapeutics against SARS-CoV-2 remains a critical need.[2] The main protease (Mpro) of SARS-CoV-2 is an essential enzyme required for viral replication and has been identified as a promising target for drug development. In this study, we report the identification of novel Mpro inhibitors, using a combination of deep reinforcement learning for de novo drug design with 3D pharmacophore/shape-based alignment and privileged fragment match count scoring components followed by hit expansions and molecular docking approaches. Our experimentally validated results show that 3 novel series exhibit potent inhibitory activity against SARS-CoV-2 Mpro, with IC50 values ranging from 1.3 uM to 2.3 uM and a high degree of selectivity. These findings represent promising starting points for the development of new antiviral therapies against COVID-19.

molecular biology↗

bioRxiv2023

The Giant Clam Photosymbiosis is a Physically Optimal Photoconversion System for the Most Intense Sunlight on Earth

Giant clams are photosymbiotic with unicellular algae ("zooxanthellae") organized in the clams mantle tissue. This tissue has an especially low albedo for a photosynthetic system, generally less than 10% at all visible wavelengths. This efficient absorbance of light occurs in the ecological context of the high solar irradiances in intertidal habitats near the equator. At these light levels, photosynthetic systems typically adapt to absorb less light in order to prevent radiative damage to chloroplasts. Giant clams are therefore unusual. If the giant clam photosymbiosis proves to be simultaneously efficient at absorption and at phototransduction at these irradiances, they are potentially remarkably productive and an important source of bioinspiration. We showed previously that the clams organize algae into vertical pillars in the mantle tissue. The clams iridocytes, or optically structured skin cells on the surface of the tissue, then function to evenly distribute incoming solar irradiance along the vertical faces of the pillars. The result is that zooxanthellae in the system absorb solar power at lower rates than that of incoming solar flux. The overall energetic performance of this phtooconversion scheme has, however, been difficult to characterize given the complex three-dimensional structure and the fact that it is coupled to a much more voluminous, respiring animal. Here we use a combination of photochemical characterization and new quantitative modeling of data from the literature to estimate the photochemical efficiency as a function of incoming irradiance of the initial electron-transfer events. Our approach is to consider the clam mantle tissue in isolation as a meta-material for photoconversion. To do this, we developed a method to directly measure the systems photochemical efficiency with spatial resolution of 10s of microns using optical microprobes threaded through the tissue. These experimental efficiency data then serve as ground-truthing for a subsequent reanalysis of photosynthesis-irradiance curves of clams taken from the literature. For this quantitative re-analysis, we incorporated the clam systems quantum efficiency as a function of irradiance per cell into a Monte Carlo model of radiative transfer among cells to find the tissues area-specific oxygen evolution apart from any sinks. We found that cells located within the dense clam system had fluorescence transients (i.e., Kautsky curves 1), a direct measure of the efficiency of PS II) that were very slow and of low intensity, particularly for a dense system, consistent with photochemical efficiencies generally greater than 50% and often greater than 90%. When incorporated into a larger computational model, we found that mature Tridacnid clams can efficiently perform photoconversion of light energy into chemical energy at light intensities many times more intense than the maximum time-averaged environmental radiance, or even the solar constant. The intensities to which the clam is adapted, however, can be found in strong wave-lensed pulses of irradiance that are characteristic of the clams habitats. This surprising result makes sense if the system has evolved to both avoid damage from and utilize the power in the intense pulses of light that result from wave-lensing. Our model predicts that by evolving to compensate for the intense pulses of solar energy produced by wave-lensing, the clam system can perform photochemical conversion of radiation at intensities many times greater than the solar constant at around 90% quantum efficiency. This result in turn suggest a strategy for engineered organic and biological composite materials performing photoconversion under solar concentration. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/530416v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@52764borg.highwire.dtl.DTLVardef@1d453d6org.highwire.dtl.DTLVardef@cc461dorg.highwire.dtl.DTLVardef@10f32f2_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2019

Adaptive thermogenesis in mice requires adipocyte light-sensing via Opsin 3

Almost all life forms can decode light information for adaptive advantage. Examples include the visual system, where photoreceptor signals are interpreted as images, and the circadian system, where light entrains a physiological clock. Here we describe a local, non-visual light response in mice that employs encephalopsin (OPN3, a 480 nm, blue light responsive opsin) to regulate the function of adipocytes. Germ line null and adipocyte-specific conditional null mice show a deficit in thermogenesis that is phenocopied in mice under blue-light deficient conditions. We show that blue light stimulation of adipocytes activates hormone sensitive lipase, the rate limiting enzyme in the lipolysis pathway, and that this is OPN3-dependent. Opn3 adipocyte conditional null mice also use reduced levels of fat mass when fasted and cold exposed further suggesting a lipolysis deficit. These data suggest the hypothesis that in mice, a local, OPN3-dependent light response in adipocytes is a mechanism for regulation of energy homeostasis.

physiology↗

bioRxiv2018

Pollen Patterns Form from Modulated Phases

Pollen grains are known for their impressive variety of species-specific, microscale surface patterning. Despite having similar biological developmental steps, pollen grain surface features are remarkably geometrically varied. Previous work suggests that a physical process may drive this pattern formation and that the observed diversity of patterns can be explained by viewing pollen pattern development as a phase transition to a spatially modulated phase. Several studies have shown that the polysaccharide material of plant cell walls undergoes phase separation in the absence of cross-linking stabilizers of the mixed phase. Here we show experimental evidence that phase separation of the extracellular polysaccharide material (primexine) during pollen cell development leads to a spatially modulated phase. The spatial pattern of this phase-separated primexine is also mechanically coupled to the undulation of the pollen cell membrane. The resulting patterned pools of denser primexine form the negative template of the ultimate sites of sporopollenin deposition, leading to the final micropattern observed in the mature pollen. We then present a general physical model of pattern formation via modulated phases. Using analytical and numerical techniques, we find that most of the pollen micropatterns observed in biological evolution could result from a physical process of modulated phases. However, an analysis of the relative rates of transitions from states that are equilibrated to or from states that are not equilibrated suggests that while equilibrium states of this process have occurred throughout evolutionary history, there has been no particular evolutionary selection for symmetric, equilibrated states.

biophysics↗