Integration of Chemosensory Pathways in the Drosophila Second-Order Olfactory Centers

AbstractBackground: Behavioral responses to odorants require neurons of the higher olfactory centers to integrate signals detected by different chemosensory neurons. Recent studies revealed stereotypic arborizations of second-order olfactory neurons from the primary olfactory center to the secondary centers, but how third-order neurons read this odor map remained unknown.Results: Using the Drosophila brain as a model system, we analyzed the connectivity patterns between second-order and third-order olfactory neurons. We first isolated three common projection zones in the two secondary centers, the mushroom body (MB) and the lateral horn (LH). Each zone receives converged information via second-order neurons from particular subgroups of antennal-lobe glomeruli. In the MB, third-order neurons extend their dendrites across various combinations of these zones, and axons of this heterogeneous population of neurons converge in the output region of the MB. In contrast, arborizations of the third-order neurons in the LH are constrained within a zone. Moreover, different zones of the LH are linked with different brain areas and form preferential associations between distinct subsets of antennal-lobe glomeruli and higher brain regions.Conclusions: MB is known to be an indispensable site for olfactory learning and memory, whereas LH function is reported to be sufficient for mediating direct nonassociative responses to odors. The structural organization of second-order and third-order neurons suggests that MB is capable of integrating a wide range of odorant information across glomeruli, whereas relatively little integration between different subsets of the olfactory signal repertoire is likely to occur in the LH

The neural basis of Drosophila gravity-sensing and hearing

The neural substrates that the fruitfly Drosophila uses to sense smell, taste and light share marked structural and functional similarities with ours, providing attractive models to dissect sensory stimulus processing. Here we focus on two of the remaining and less understood prime sensory modalities: graviception and hearing. We show that the fly has implemented both sensory modalities into a single system, Johnston's organ, which houses specialized clusters of mechanosensory neurons, each of which monitors specific movements of the antenna. Gravity- and sound-sensitive neurons differ in their response characteristics, and only the latter express the candidate mechanotransducer channel NompC. The two neural subsets also differ in their central projections, feeding into neural pathways that are reminiscent of the vestibular and auditory pathways in our brain. By establishing the Drosophila counterparts of these sensory systems, our findings provide the basis for a systematic functional and molecular dissection of how different mechanosensory stimuli are detected and processed

Glueball mass from quantized knot solitons and gauge-invariant gluon mass

We propose an approach which enables one to obtain simultaneously the glueball mass and the gluon mass in the gauge-invariant way to shed new light on the mass gap problem in Yang-Mills theory. First, we point out that the Faddeev (Skyrme--Faddeev-Niemi) model can be induced through the gauge-invariant vacuum condensate of mass dimension two from SU(2) Yang-Mills theory. Second, we obtain the glueball mass spectrum by performing the collective coordinate quantization of the topological knot soliton in the Faddeev model. Third, we demonstrate that a relationship between the glueball mass and the gluon mass is obtained, since the gauge-invariant gluon mass is also induced from the relevant vacuum condensate. Finally, we determine physical values of two parameters in the Faddeev model and give an estimate of the relevant vacuum condensation in Yang-Mills theory. Our results indicate that the Faddeev model can play the role of a low-energy effective theory of the quantum SU(2) Yang-Mills theory.Comment: 17 pages, 2 figures, 3 tables; a version accepted for publication in J. Phys. A: Math. Gen.; Sect. 2 and sect. 5 (old sect. 4) are modified. Sect. 4, Tables 1 and Table 3 are adde

Magnetic monopoles and center vortices as gauge-invariant topological defects simultaneously responsible for confinement

We give a gauge-invariant definition of the vortex surface in SU(N) Yang-Mills theory without using the gauge fixing procedure. In this construction, gauge-invariant magnetic monopoles with fractional magnetic charges emerge in the boundary of the non-oriented vortex surface such that the asymptotic string tension reproduces the correct $N$-ality dependence. We show that gauge-invariant magnetic monopoles and vortices are simultaneously responsible for quark confinement in four dimensional spacetime based on the Wilson criterion. These results are extracted from a non-Abelian Stokes theorem derived in the previous paper.Comment: 20 (Cover+19) pages, 3 figures; version to be published in J. Phys. G: Nucl. Part. Phy

SILVERRUSH. VII. Subaru/HSC Identifications of 42 Protocluster Candidates at z~6-7 with the Spectroscopic Redshifts up to z=6.574: Implications for Cosmic Reionization

We report fourteen and twenty-eight protocluster candidates at z=5.7 and 6.6 over 14 and 19 deg^2 areas, respectively, selected from 2,230 (259) Lya emitters (LAEs) photometrically (spectroscopically) identified with Subaru/Hyper Suprime-Cam (HSC) deep images (Keck, Subaru, and Magellan spectra and the literature data). Six out of the 42 protocluster candidates include 1-12 spectroscopically confirmed LAEs at redshifts up to z=6.574. By the comparisons with the cosmological Lya radiative transfer (RT) model reproducing LAEs with the reionization effects, we find that more than a half of these protocluster candidates are progenitors of the present-day clusters with a mass of > 10^14 M_sun. We then investigate the correlation between LAE overdensity delta and Lya rest-frame equivalent width EW_Lya^rest, because the cosmological Lya RT model suggests that a slope of EW_Lya^rest-delta relation is steepened towards the epoch of cosmic reionization (EoR), due to the existence of the ionized bubbles around galaxy overdensities easing the escape of Lya emission from the partly neutral intergalactic medium (IGM). The available HSC data suggest that the slope of the EW_Lya^rest-delta correlation does not evolve from the post-reionization epoch z=5.7 to the EoR z=6.6 beyond the moderately large statistical errors. There is a possibility that we would detect the evolution of the EW_Lya^rest - delta relation from z=5.7 to 7.3 by the upcoming HSC observations providing large samples of LAEs at z=6.6-7.3

Location and arrangement of campaniform sensilla in Drosophila melanogaster

Sensory systems provide input to motor networks on the state of the body and environment. One such sensory system in insects is the campaniform sensilla (CS), which detect deformations of the exoskeleton arising from resisted movements or external perturbations. When physical strain is applied to the cuticle, CS external structures are compressed, leading to transduction in an internal sensory neuron. In Drosophila melanogaster, the distribution of CS on the exoskeleton has not been comprehensively described. To investigate CS number, location, spatial arrangement, and potential differences between individuals, we compared the front, middle, and hind legs of multiple flies using scanning electron microscopy. Additionally, we imaged the entire body surface to confirm known CS locations. On the legs, the number and relative arrangement of CS varied between individuals, and single CS of corresponding segments showed characteristic differences between legs. This knowledge is fundamental for studying the relevance of cuticular strain information within the complex neuromuscular networks controlling posture and movement. This comprehensive account of all D. melanogaster CS helps set the stage for experimental investigations into their responsivity, sensitivity, and roles in sensory acquisition and motor control in a light-weight model organism

Interaction between NANOS2 and the CCR4-NOT Deadenylation Complex Is Essential for Male Germ Cell Development in Mouse

Nanos is one of the evolutionarily conserved proteins implicated in germ cell development and we have previously shown that it interacts with the CCR4-NOT deadenylation complex leading to the suppression of specific RNAs. However, the molecular mechanism and physiological significance of this interaction have remained elusive. In our present study, we identify CNOT1, a component of the CCR4-NOT deadenylation complex, as a direct factor mediating the interaction with NANOS2. We find that the first 10 amino acids (AAs) of NANOS2 are required for this binding. We further observe that a NANOS2 mutant lacking these first 10 AAs (NANOS2-ΔN10) fails to rescue defects in the Nanos2-null mouse. Our current data thus indicate that the interaction with the CCR4-NOT deadenylation complex is essential for NANOS2 function. In addition, we further demonstrate that NANOS2-ΔN10 can associate with specific mRNAs as well as wild-type NANOS2, suggesting the existence of other NANOS2-associated factor(s) that determine the specificity of RNA-binding independently of the CCR4-NOT deadenylation complex

HIV-1 competition experiments in humanized mice show that APOBEC3H imposes selective pressure and promotes virus adaptation

APOBEC3 (A3) family proteins are DNA cytosine deaminases recognized for contributing to HIV-1 restriction and mutation. Prior studies have demonstrated that A3D, A3F, and A3G enzymes elicit a robust anti-HIV-1 effect in cell cultures and in humanized mouse models. Human A3H is polymorphic and can be categorized into three phenotypes: stable, intermediate, and unstable. However, the anti-viral effect of endogenous A3H in vivo has yet to be examined. Here we utilize a hematopoietic stem cell-transplanted humanized mouse model and demonstrate that stable A3H robustly affects HIV-1 fitness in vivo. In contrast, the selection pressure mediated by intermediate A3H is relaxed. Intriguingly, viral genomic RNA sequencing reveled that HIV-1 frequently adapts to better counteract stable A3H during replication in humanized mice. Molecular phylogenetic analyses and mathematical modeling suggest that stable A3H may be a critical factor in human-to-human viral transmission. Taken together, this study provides evidence that stable variants of A3H impose selective pressure on HIV-1

A prospective compound screening contest identified broader inhibitors for Sirtuin 1

Potential inhibitors of a target biomolecule, NAD-dependent deacetylase Sirtuin 1, were identified by a contest-based approach, in which participants were asked to propose a prioritized list of 400 compounds from a designated compound library containing 2.5 million compounds using in silico methods and scoring. Our aim was to identify target enzyme inhibitors and to benchmark computer-aided drug discovery methods under the same experimental conditions. Collecting compound lists derived from various methods is advantageous for aggregating compounds with structurally diversified properties compared with the use of a single method. The inhibitory action on Sirtuin 1 of approximately half of the proposed compounds was experimentally accessed. Ultimately, seven structurally diverse compounds were identified