Pricehorton8840

Male and female animals typically display innate sex-specific mating behaviors, which, in vertebrates, are highly dependent on sex steroid signaling. While estradiol-17β (E2) signaling through estrogen receptor 2 (ESR2) serves to defeminize male mating behavior in rodents, the available evidence suggests that E2 signaling is not required in teleosts for either male or female mating behavior. Here, we report that female medaka deficient for Esr2b, a teleost ortholog of ESR2, are not receptive to males but rather court females, despite retaining normal ovarian function with an unaltered sex steroid milieu. Thus, contrary to both prevailing views in rodents and teleosts, E2/Esr2b signaling in the brain plays a decisive role in feminization and demasculinization of female mating behavior and sexual preference in medaka. Further behavioral testing showed that mutual antagonism between E2/Esr2b signaling and androgen receptor-mediated androgen signaling in adulthood induces and actively maintains sex-typical mating behaviors and preference. Our results also revealed that the female-biased sexual dimorphism in esr2b expression in the telencephalic and preoptic nuclei implicated in mating behavior can be reversed between males and females by altering the sex steroid milieu in adulthood, likely via mechanisms involving direct E2-induced transcriptional activation. In addition, Npba, a neuropeptide mediating female sexual receptivity, was found to act downstream of E2/Esr2b signaling in these brain nuclei. Collectively, these functional and regulatory mechanisms of E2/Esr2b signaling presumably underpin the neural mechanism for induction, maintenance, and reversal of sex-typical mating behaviors and sexual preference in teleosts, at least in medaka.Goal-directed behavior requires integrating sensory information with prior knowledge about the environment. Behavioral biases that arise from these priors could increase positive outcomes when the priors match the true structure of the environment, but mismatches also happen frequently and could cause unfavorable outcomes. Biases that reduce gains and fail to vanish with training indicate fundamental suboptimalities arising from ingrained heuristics of the brain. Here, we report systematic, gain-reducing choice biases in highly trained monkeys performing a motion direction discrimination task where only the current stimulus is behaviorally relevant. The monkey's bias fluctuated at two distinct time scales slow, spanning tens to hundreds of trials, and fast, arising from choices and outcomes of the most recent trials. Our findings enabled single trial prediction of biases, which influenced the choice especially on trials with weak stimuli. The pre-stimulus activity of neuronal ensembles in the monkey prearcuate gyrus represented these biases as an offset along the decision axis in the state space. This offset persisted throughout the stimulus viewing period, when sensory information was integrated, leading to a biased choice. The pre-stimulus representation of history-dependent bias was functionally indistinguishable from the neural representation of upcoming choice before stimulus onset, validating our model of single-trial biases and suggesting that pre-stimulus representation of choice could be fully defined by biases inferred from behavioral history. Our results indicate that the prearcuate gyrus reflects intrinsic heuristics that compute bias signals, as well as the mechanisms that integrate them into the oculomotor decision-making process.In Gram-negative bacteria, the β-barrel assembly machinery (BAM) complex catalyses the assembly of β-barrel proteins into the outer membrane, and is composed of five subunits BamA, BamB, BamC, BamD and BamE. Once assembled, - β-barrel proteins can be involved in various functions including uptake of nutrients, export of toxins and mediating host-pathogen interactions, but the precise mechanism by which these ubiquitous and often essential β-barrel proteins are assembled is yet to be established. In order to determine the relative positions of BAM subunits in the membrane environment we reconstituted each subunit into a biomimetic membrane, characterizing their interaction and structural changes by Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) and neutron reflectometry. Our results suggested that the binding of BamE, or a BamDE dimer, to BamA induced conformational changes in the polypeptide transported-associated (POTRA) domains of BamA, but that BamB or BamD alone did not promote any such changes. As monitored by neutron reflectometry, addition of an unfolded substrate protein extended the length of POTRA domains further away from the membrane interface as part of the mechanism whereby the substrate protein was folded into the membrane.Dihydrodipicolinate synthase (DHDPS) catalyzes the first step in the biosynthetic pathway for production of l-lysine in bacteria and plants. The enzyme has received interest as a potential drug target owing to the absence of the enzyme in mammals. The DHDPS reaction is the rate limiting step in lysine biosynthesis and involves the condensation of l-aspartate-β-semialdehyde and pyruvate to form 2, 3-dihydrodipicolinate. 2, 4-oxo-pentanoic acid (acetopyruvate) is a slow-binding inhibitor of DHDPS that is competitive versus pyruvate with an initial Ki of about 20 μM and a final inhibition constant of about 1.4 μM. The enzymeacetopyruvate complex displays an absorbance spectrum with a λmax at 304 nm and a longer wavelength shoulder. The rate constant for formation of the complex is 86 M-1 s-1. The enzyme forms a covalent enamine complex with the first substrate pyruvate and can be observed spectrally with a λmax at 271 nm. INCB024360 solubility dmso The spectra of the enzyme in the presence of pyruvate and acetopyruvate shows the initial formation of the pyruvate enamine intermediate followed by the slower appearance of the Eacetopyruvate spectra with a rate constant of about 0.013 s-1. The spectral studies suggest the formation of a Schiff base between acetopyruvate and K161 on enzyme that subsequently deprotonates to form a resonance stabilized anion similar to the enamine intermediate formed with pyruvate. The crystal structure of the Eacetopyruvate complex confirms the formation of the Schiff base between acetopyruvate and K161.