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Role of 5’ - 3’ exoribonuclease Xrn1 in energy expenditure and control of obesity
Get PDFOkinawa Institute of Science and Technology Graduate UniversityDoctor of PhilosophyGene expression of eukaryotes is regulated by various processes including mRNA degradation. Dysregulation of mRNA degradation is now considered to be a possible cause of various disease including cancer, neurodegenerative disease, diabetes, and obesity. 5’ - 3’ exoribonuclease Xrn1 functions at the last step of mRNA degradation. Recent studies showed that Xrn1 forms specific cytoplasmic messenger ribonucleoprotein (mRNP) granules in postsynapse to regulate local translation. However, there are no physiological studies that have investigated the function of Xrn1 in the brain. Therefore, I generated forebrain specific Xrn1 knockout mice for the first time and analyzed their phenotype. Interestingly, the knockout mice showed obesity and hyperphagia. Energy homeostasis is regulated by various organs including central nervous systems and peripheral metabolic tissues such as liver, pancreas, and adipose tissues, thus the development of obesity is often caused by the dysregulation of inter-organ communication. In response to metabolic cues, peripheral tissues produce hormones such as insulin and leptin. The hypothalamus sense changes in circulating blood glucose, insulin, and leptin and integrate those cues to maintain metabolic homeostasis. Blood analysis showed that the conditional Xrn1 knockout mice were hyperglycemic, hyperleptinemic, and hyperinsulinemic. Consistent with the above phenotype, I observed dysregulated expression of appetite and energy homeostasis related genes in the hypothalamus of the knockout mice. These data suggest that Xrn1 is required for the regulation of appetite and energy homeostasis related gene expression in the hypothalamus, and thus Xrn1 plays a role in energy expenditure and control of obesity.doctoral thesi
Evolutionary rates are correlated between cockroach symbionts and mitochondrial genomes
Get PDFBacterial endosymbionts evolve under strong host-driven selection. Factors influencing host evolution might affect symbionts in similar ways, potentially leading to correlations between the molecular evolutionary rates of hosts and symbionts. Although there is evidence of rate correlations between mitochondrial and nuclear genes, similar investigations of hosts and symbionts are lacking. Here, we demonstrate a correlation in molecular rates between the genomes of an endosymbiont (Blattabacterium cuenoti) and the mitochondrial genomes of their hosts (cockroaches). We used partial genome data for multiple strains of B. cuenoti to compare phylogenetic relationships and evolutionary rates for 55 cockroach/symbiont pairs. The phylogenies inferred for B. cuenoti and the mitochondrial genomes of their hosts were largely congruent, as expected from their identical maternal and cytoplasmic mode of inheritance. We found a correlation between evolutionary rates of the two genomes, based on comparisons of root-to-tip distances and on comparisons of the branch lengths of phylogenetically independent species pairs. Our results underscore the profound effects that long-term symbiosis can have on the biology of each symbiotic partner.journal articl
Asymmetric flow of polymer solutions around microfluidic cylinders: Interaction between shear-thinning and viscoelasticity
Get PDFViscoelastic flow around a cylinder is a model problem representing a wide range of relevant industrial processing and biological applications. Reducing the cylinder to microscopic dimensions conveniently enables the problem to be examined in the absence of inertia. Recently, we have developed glass microfluidic geometries containing long and slender, yet rigidly fixed, microfluidic cylinders, which present a low blockage ratio β=2r/W=0.1, where r=20μm is the cylinder radius and W=400μm is the channel width. Using a shear-banding viscoelastic wormlike micellar (WLM) solution, we showed how the flow around such a cylinder could destabilize beyond a critical Weissenberg number (Wi=λU/r, where λ is a characteristic time of the fluid and U is the average flow velocity), resulting in the asymmetric division of the fluid around either side of the cylinder [Haward et al, Soft Matter 15:1927]. In the present work we investigate this flow instability in greater detail using a range of polymer solutions formulated from hydrolyzed poly(acrylamide) (HPAA) dissolved at different concentrations in deionized water. The test fluids present a range of shear-thinning responses under steady shear, and also a wide variety of characteristic times. At low HPAA concentrations, the flow around the cylinder remains essentially symmetric for all Wi, but as the concentration increases, so does the maximum degree of the flow asymmetry observed with increasing Wi. Interestingly, at intermediate concentrations, the flow can resymmetrize at very high Wi. We understand these effects by considering simultaneously both the degree of shear-thinning of the fluid and the imposed Wi, and our analysis shows that both strong shear-thinning and high elasticity are required for the formation of strongly asymmetric flows. Our results represent the first report of this highly asymmetric flow state in polymer solutions, showing that it is a general phenomenon and not only specific to WLM. Our analysis provides a clear insight into the origins of this unusual flow state and may also be relevant to understanding other instances of asymmetries arising in shear-thinning viscoelastic flows.journal articl
Where Is the Action in Perception? An Exploratory Study With a Haptic Sensory Substitution Device
Get PDFEnactive cognitive science (ECS) and ecological psychology (EP) agree that active movementisimportant forperception,butthey remainambiguousregardingtheprecise role of agency. EP has focused on the notion of sensorimotor invariants, according to which bodily movements play an instrumental role in perception. ECS has focused on the notion of sensorimotor contingencies, which goes beyond an instrumental role because skillfully regulated movements are claimed to play a constitutive role. We refer to these two hypotheses as instrumental agency and constitutive agency, respectively. Evidence comes from a variety of fields, including neural, behavioral, and phenomenological research, but so far with confounds that prevent an experimental distinction between these hypotheses. Here we advance the debate by proposing a novel double-participant setup that aims to isolate agency as the key variable that distinguishes bodily movement in active and passive conditions of perception. We pilot this setup with a psychological study of width discrimination using the Enactive Torch, a haptic sensory substitution device. There was no evidence favoring the stronger hypothesis of constitutive agency over instrumental agency. However, we caution that during debriefing several participants reported using cognitive strategies that did not rely on spatial perception. We conclude that this approach is a viable direction for future research, but that greater care is required to establish and confirm the desired modality of first-person experience.journal articl
Investigating real-time social interaction in pairs of adolescents with the Perceptual Crossing Experiment
Get PDFThe study of real-time social interaction provides ecologically valid insight into social behavior. The objective of the current research is to experimentally assess real-time social contingency detection in an adolescent population, using a shortened version of the Perceptual Crossing Experiment (PCE). Pairs of 148 adolescents aged between 12 and 19 were instructed to find each other in a virtual environment interspersed with other objects by interacting with each other using tactile feedback only. Across six rounds, participants demonstrated increasing accuracy in social contingency detection, which was associated with increasing subjective experience of the mutual interaction. Subjective experience was highest in rounds when both participants were simultaneously accurate in detecting each other's presence. The six-round version yielded comparable social contingency detection outcome measures to a ten-round version of the task. The shortened six-round version of the PCE has therefore enabled us to extend the previous findings on social contingency detection in adults to an adolescent population, enabling implementation in prospective research designs to assess the development of social contingency detection over time.journal articl
Stiffness of the human foot and evolution of the transverse arch
Get PDFThe stiff human foot enables an efficient push-off when walking or running, and was critical for the evolution of bipedalism(1-6). The uniquely arched morphology of the human midfoot is thought to stiffen it(5-9), whereas other primates have flat feet that bend severely in the midfoot(7,10,11). However, the relationship between midfoot geometry and stiffness remains debated in foot biomechanics(12,13), podiatry(14,15) and palaeontology(4-6). These debates centre on the medial longitudinal arch(5,6) and have not considered whether stiffness is affected by the second, transverse tarsal arch of the human foot(16). Here we show that the transverse tarsal arch, acting through the inter-metatarsal tissues, is responsible for more than 40% of the longitudinal stiffness of the foot. The underlying principle resembles a floppy currency note that stiffens considerably when it curls transversally. We derive a dimensionless curvature parameter that governs the stiffness contribution of the transverse tarsal arch, demonstrate its predictive power using mechanical models of the foot and find its skeletal correlate in hominin feet. In the foot, the material properties of the inter-metatarsal tissues and the mobility of the metatarsals may additionally influence the longitudinal stiffness of the foot and thus the curvature-stiffness relationship of the transverse tarsal arch. By analysing fossils, we track the evolution of the curvature parameter among extinct hominins and show that a human-like transverse arch was a key step in the evolution of human bipedalism that predates the genus Homo by at least 1.5 million years. This renewed understanding of the foot may improve the clinical treatment of flatfoot disorders, the design of robotic feet and the study of foot function in locomotion.journal articl
Characterization of Acantharea-Phaeocystis photosymbioses: distribution, abundance, specificity, maintenance and host-control
Get PDFOkinawa Institute of Science and Technology Graduate UniversityDoctor of PhilosophyMicrobial eukaryotes (protists) are important contributors to marine biogeochemistry and play essential roles as both producers and consumers in marine ecosystems. Among protists, mixotrophs—those that use both heterotrophy and autotrophy to meet their energy requirements—are especially important to primary production in low-nutrient regions. Acantharian protists (clades E & F) accomplish mixotrophy by hosting Phaeocystis spp. as algal endosymbionts and are extremely abundant in subtropical low-nutrient regions where they form productivity hotspots. Despite their ecological importance, acantharians remain understudied due to their structural fragility and inability to survive in culture. In order to overcome these challenges and illuminate key aspects of acantharian biology and ecology—including distribution, abundance, and specificity and specialization of symbioses—single-cell RNA sequencing methods were developed for acantharians and used alongside environmental metabarcode sequencing and high-throughput, in-situ imaging. Major findings from this thesis were that i) acantharian cell (> 250 µm) concentrations decrease with depth, which correlates to patterns in relative sequence abundances for acantharian clades with known morphologies but not for those lacking known morphology, and that ii) while individual acantharians simultaneously harbor multiple symbiont species, intra-host symbiont communities do not match environmental communities, providing evidence for multiple uptake events but against continuous symbiont turnover, and that iii) photosynthesis genes are upregulated in symbiotic Phaeocystis, reflecting enhanced productivity in symbiosis, but DNA replication and cell-cycle genes are downregulated, demonstrating that hosts suppress symbiont cell division. Moreover, storage carbohydrate and lipid biosynthesis and metabolism genes are downregulated in symbiotic Phaeocystis, suggesting fixed carbon is relinquished to acantharian hosts. Gene expression patterns indicate that symbiotic Phaeocystis is not nutrient limited and likely benefits from host-supplied ammonium and urea, thus providing evidence for nutrient transfer between hosts and symbionts. Interestingly, genes associated with protein kinase signaling pathways that promote cell proliferation are downregulated in symbiotic Phaeocystis. Deactivation of these genes may prevent symbionts from overgrowing hosts and therefore represents a key component of maintaining the symbiosis. This research contributes new insights into the ecologically relevant photosymbioses between Acantharea and Phaeocystis and illustrates the benefits of combining single-cell sequencing and imaging technologies to illuminate important microbial relationships in marine ecosystems.doctoral thesi
Effects of coherence on quantum speed limits and shortcuts to adiabaticity in many-particle systems
Get PDFWe discuss the effects of many-body coherence on the speed of evolution of ultracold atomic gases and the relation to quantum speed limits. Our approach is focused on two related systems, spinless fermions and the bosonic Tonks-Girardeau gas, which possess equivalent density dynamics but very different coherence properties. To illustrate the effect of the coherence on the dynamics, we consider squeezing an anharmonic potential which confines the particles and find that the speed of the evolution exhibits subtle but fundamental differences between the two systems. Furthermore, we explore the difference in the driven dynamics by implementing a shortcut to adiabaticity designed to reduce spurious excitations. We show that collisions between the strongly interacting bosons can lead to changes in the coherence which result in different evolution speeds and therefore different fidelities of the final states.journal articl
BMS symmetry of celestial OPE
Get PDFIn this paper we study the BMS symmetry of the celestial OPE of two positive helicity gravitons in Einstein theory in four dimensions. The celestial OPE is obtained by Mellin transforming the scattering amplitude in the (holomorphic) collinear limit. The collinear limit at leading order gives the singular term of the celestial OPE. We compute the first subleading correction to the OPE by analysing the four graviton scattering amplitude directly in Mellin space. The subleading term can be written as a linear combination of BMS descendants with the OPE coefficients determined by BMS algebra and the coefficient of the leading term in the OPE. This can be done by defining a suitable BMS primary state. We find that among the descendants, which appear at the first subleading order, there is one which is created by holomorphic supertranslation with simple pole on the celestial sphere.journal articl
Colonize, radiate, decline: Unraveling the dynamics of island community assembly with Fijian trap‐jaw ants
Get PDFThe study of island community assembly has been fertile ground for developing and testing theoretical ideas in ecology and evolution. The ecoevolutionary trajectory of lineages after colonization has been a particular interest, as this is a key component of understanding community assembly. In this system, existing ideas, such as the taxon cycle, posit that lineages pass through a regular sequence of ecoevolutionary changes after colonization, with lineages shifting toward reduced dispersal ability, increased ecological specialization, and declines in abundance. However, these predictions have historically been difficult to test. Here, we integrate phylogenomics, population genomics, and X-ray microtomography/3D morphometrics, to test hypotheses for whether the ecomorphological diversity of trap-jaw ants (Strumigenys) in the Fijian archipelago is assembled primarily through colonization or postcolonization radiation, and whether species show ecological shifts toward niche specialization, toward upland habitats, and decline in abundance after colonization. We infer that most Fijian endemic Strumigenys evolved in situ from a single colonization and have diversified to fill a large fraction of global morphospace occupied by the genus. Within this adaptive radiation, lineages trend to different degrees toward high elevation, reduced dispersal ability, and demographic decline, and we find no evidence of repeated colonization that displaces the initial radiation. Overall these results are only partially consistent with taxon cycle and associated ideas, while highlighting the potential role of priority effects in assembling island communities.journal articl