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Noh, S.

Publications and source records attributed to Noh, S..

8 recordsLinked to original sources

A quantum interface with mitochondrial bioenergetics

Summary ParagraphRecent work has shown that genetically engineered proteins can serve as quantum bits in living systems. These quantum bits arise from the photochemistry of protein-bound flavins: blue-light excitation drives electron transfer to form a spin-correlated radical pair whose coherent singlet-triplet interconversion makes the proteins fluorescence sensitive to weak magnetic fields. Because this radical-pair reaction depends on the redox state of the flavin--itself a central electron carrier in cellular metabolism--the magneto-fluorescence of a biological qubit is intrinsically coupled to the biochemistry around it. This suggests a powerful application of fundamental significance in biology, until now an unsolved problem in the field of quantum sensing. Here we show a new class of quantum sensor, mtMagLOV2, that interfaces directly to a defining feature of life itself: the bioenergetic state of the cell. We genetically engineer flavin mononucleotide (FMN)-containing, magnetic-field-sensitive fluorescent proteins ("biological qubits") to be expressed and translocated into the key bioenergetic machinery of the cell: the mitochondrial matrix. Using confocal and super-resolution microscopy, mtMagLOV2 localizes to the mitochondrial cristae, home of the electron transport chain complexes I-V and ATP synthase--the site of oxidative phosphorylation (OXPHOS). By pharmacological manipulation of OXPHOS, we show that the sensors magneto-fluorescence tracks the redox (oxidation-reduction) state of the mitochondrial flavins, providing a quantum readout of redox status. The response differs between cancer cells (which rely heavily on glycolysis) and cardiomyocytes (which rely predominantly on OXPHOS), demonstrating "quantum bioenergetic profiling". Together, these results establish biological qubits as quantum sensors capable of probing mitochondrial bioenergetics, opening a quantum window into the energetic machinery of living cells. More broadly, we anticipate that coupling quantum redox sensitivity to specific biochemical targets will extend the reach of quantum technologies across the life sciences.

biophysics↗

Characterization and analysis of neuronal signaling using microelectrode array combined with rapid and localized cooling device for cryo-neuromodulation

Cryoanesthesia--a purely physical anesthesia treatment that freezes tissue and attenuate nerve activity--can provide fast treatment through freezing and thawing of cryo-machine and is inexpensive compared to other anesthetics. However, cryoanesthesia has not been widely adopted because securing safe and effective conditions requires quantitative measurement and analysis of neuronal signaling during freezing and recovery, for which research tools are limited. A lack of rapid and localized cooling technologies for quantitative cellular level analysis, in particular, hinders research on not only the optimal cryo-modulation of neuronal activities but also its influence to neighboring cells via cellular networks. Here, we introduce a novel cryo-neuromodulation platform, a high-speed precision probe-type cooling device ([~]20{degrees}C/s at cooling) that provides localized cooling combined with a microelectrode array (MEA) system. We explored the temperature conditions for efficient silencing and recovery of neuronal activities without cell damage. We found that electrical activities of neurons were fully recovered within 1 minute of cooling duration with the maximum cooling speed, which was also confirmed with calcium imaging. The impact of silenced neurons on the neighboring neural network was explored using the localized cooling and we perceived that its influence can be transmitted if the neuronal network is well organized. Our new cryo-device provides rapid and reversible control of neural activities, which allows not just quantitative analysis of the network dynamics, but also new applications in clinical settings.

neuroscience↗

Seasonally increasing parasite load is associated with microbiome dysbiosis in wild bumblebees

The microbiome is increasingly recognized for its complex relationship with host fitness. Bumblebees are host to a characteristic gut microbiome community that is derived and reinforced through social contact between individuals. The bumblebee microbiome is species-poor, and primarily composed from a small number of core taxa that are associated with the greater tribe of corbiculate bees. Experimental findings support a role for the core bumblebee microbiome in resistance to severe infections by a common trypanosomal parasite, Crithidia bombi. However, most studies have been small in scale, often considering just one or two bumblebee species, or making use of commercially-reared bees. To better understand the microbiome diversity of wild populations, we have deeply sampled field populations of ten sympatric species found throughout central and down east Maine in a three-year microbiome field survey. We have used 16S amplicon sequencing to produce microbiome community profiles, and qPCR to screen samples for infections by Crithidia bombi. The breadth of our dataset has enabled us to test for seasonal and interspecific trends in the microbiome community. Controlling for these external sources of variation, we have identified microbial factors associated with infection and parasite load that support the role of the core microbiome in resistance to severe infection.

microbiology↗

Paraburkholderia bonniea symbiont strain identity impacts amoeba host fitness and rate of horizontal transmission

In facultative symbioses, only a fraction of hosts are associated with a symbiont. Understanding why specific host and symbiont strains are associated can inform us of the evolutionary forces affecting facultative symbioses. Possibilities include ongoing host-symbiont coevolution driven by reciprocal selection, or priority effects that are neutral in respect to the host-symbiont interaction. We hypothesized that ongoing host-symbiont coevolution would lead to higher fitness estimates for naturally co-occurring (native) host and symbiont combinations compared to nonnative combinations. We used the Dictyostelium discoideum - Paraburkholderia bonniea system to test this hypothesis. P. bonniea features a reduced genome size relative to another Paraburkholderia symbiont of D. discoideum, indicating a significant history of coevolution with its host. Facultative symbionts may experience continued genome reduction if coevolution is ongoing, or their genome size may have reached a stable state if the symbiosis has also stabilized. Our work demonstrates that ongoing coevolution is unlikely for D. discoideum and P. bonniea. The system instead represents a stable facultative symbiosis. Specifically associated host and symbiont strains in this system are the result of priority effects, and presently unassociated hosts are simply uncolonized. We find evidence for a virulence-transmission trade-off without host strain specificity, and identify candidate virulence factors in the genomes of P. bonniea strains that may contribute to variation in benevolence. Lay summarySymbiotic relationships between hosts and their microbial partners are prolonged and intimate associations. Some of these relationships are obligatory for both a host and symbiont to survive, while others are facultative and each partner can survive without the other. In the latter case, some host individuals may be associated with a symbiont while others are not. Specific host and symbiont combinations can be the result of reciprocal adaptation between host and symbiont partners so that naturally co-occurring combinations are best suited for each other in terms of their biological fitness. On the other hand, the symbiont that a host is associated with may simply be the symbiont that arrived first, in what is called a priority effect. We sought to determine which possibility best explained naturally co-occurring combinations of host and symbiont strains of the social amoeba Dictyostelium discoideum and its symbiont Paraburkholderia bonniea. Our work demonstrates that D. discoideum and P. bonniea are in a stable facultative relationship. Specifically associated host and symbiont combinations are the result of priority effects, and D. discoideum hosts without symbionts are simply uncolonized. This work fills a gap in our understanding of the evolutionary forces affecting facultative symbiotic relationships. We also show for the first time that P. bonniea symbionts can spread among amoeba hosts when they aggregate together during the social stage of their life cycle.

evolutionary biology↗

Astrocytic connection to engram neurons increased after learning

Astrocytes directly participate in learning and memory. However, the structural association between astrocytes and memory-encoding engram neurons after learning remains to be elucidated. We developed astrocyte-enhanced green fluorescent protein reconstitution across synaptic partners (eGRASP) to examine tripartite synapses between astrocytes and engram neurons. Using astrocyte-eGRASP, we found that astrocytes had increased connections to engram neurons after learning. Dendritic spines with astrocytic contacts showed enhanced morphology. Live-cell imaging of astrocyte-eGRASP revealed that astrocytic connections are stabilized by neuronal activity. These results indicate that astrocytes distinguish contact between engram neurons and generate engram-specific contact patterns during learning.

neuroscience↗

Comparative genomics support reduced-genome Paraburkholderia symbionts of Dictyostelium discoideum amoebas are ancestrally adapted professional symbionts

The social amoeba Dictyostelium discoideum is a predatory soil protist frequently used for studying host-pathogen interactions. A subset of D. discoideum strains isolated from soil persistently carry symbiotic Paraburkholderia, recently formally described as P. agricolaris, P. bonniea, and P. hayleyella. The three facultative symbiont species of D. discoideum present a unique opportunity to study a naturally occurring symbiosis in a laboratory model protist. In addition, there is a large difference in genome size between P. agricolaris (8.7 million base pairs) vs. P. hayleyella and P. bonniea (4.1 Mbp) and in GC content (62% vs. 59%). We took a comparative genomics approach and compared the three genomes of D. discoideum-symbionts to 12 additional Paraburkholderia genomes to test for genome evolution patterns that frequently accompany host adaptation. Overall, P. agricolaris is difficult to distinguish from other Paraburkholderia based on its genome size and content, but the two reduced genomes of P. bonniea and P. hayleyella display characteristics that support evolution in a host environment. In addition, all three D. discoideum-symbiont genomes have increased secretion system and motility genes that may mediate interactions with their host. Specifically, adjacent BurBor-like type 3 and T6SS-5-like type 6 secretion system operons shared among all three D. discoideum-symbiont genomes may be important for host interaction. Ultimately, our combined evidence supports that the reduced-genome D. discoideum-symbionts have evolved to be professional symbionts ancestrally adapted to their protist hosts.

evolutionary biology↗

Sex and age differences in cognitive bias and neural activation in response to cognitive bias

Cognitive symptoms of depression, including negative cognitive bias, are more severe in women than in men. Current treatments to reduce negative cognitive bias are not effective and sex differences in the neural activity underlying cognitive bias may play a role. Here we examined sex and age differences in cognitive bias and functional connectivity in a novel paradigm. Male and female rats underwent an 18-day cognitive bias procedure, in which they learned to discriminate between two contexts (shock paired context A, no-shock paired context B), during either adolescence (postnatal day (PD 40)), young adulthood (PD 100), or middle-age (PD 210). Cognitive bias was measured as freezing behaviour in response to an ambiguous context (context C), with freezing levels akin to the shock paired context coded as negative bias. All animals learned to discriminate between the two contexts, regardless of sex or age. However, adults (young adults, middle-aged) displayed a greater negative cognitive bias compared to adolescents, and middle-aged males had a greater negative cognitive bias than middle-aged females. Females had greater neural activation of the nucleus accumbens, amygdala, and hippocampal regions to the ambiguous context compared to males, and young rats (adolescent, young adults) had greater neural activation in these regions compared to middle-aged rats. Functional connectivity between regions involved in cognitive bias differed by age and sex, and only adult males had negative correlations between the frontal regions and hippocampal regions. These findings highlight the importance of examining age and sex when investigating the underpinnings of negative cognitive bias and lay the groundwork for determining what age- and sex-specific regions to target in future cognitive bias studies. HighlightsO_LIMiddle-aged males had a greater negative cognitive bias than middle-aged females C_LIO_LIAdult rats displayed a greater negative cognitive bias compared to adolescents C_LIO_LIGreater neural activity in females than males in limbic and reward regions C_LIO_LIGreater role of the frontal cortex activation in the cognitive bias of adults C_LIO_LIFunctional connectivity in response to cognitive bias differed by age and sex C_LI

neuroscience↗

Endosymbiotic adaptations in three new bacterial species associated with Dictyostelium discoideum: Burkholderia agricolaris sp. nov., Burkholderia hayleyella sp. nov., and Burkholderia bonniea sp. nov.

Here we name three species of Burkholderia that can defeat the mechanisms by which bacteria are normally excluded from the spores of a soil dwelling eukaryote Dictyostelium discoideum, which is predatory on bacteria. They are B. agricolaris sp. nov., B. hayleyella sp. nov., and B. bonniea sp. nov. These new species are widespread across the eastern USA and were isolated as internal symbionts of wild collected D. discoideum. Evidence that they are each a distinct new species comes from their phylogenetic position, carbon usage, reduced cell length, cooler optimal growth temperature, and ability to invade D. discoideum amoebae and remain there for generations.

microbiology↗