Editorial: The roles of micro-RNAs in neuroendocrine systems

International audienc

Imprinting modulates processing of visual information in the visual wulst of chicks

BACKGROUND: Imprinting behavior is one form of learning and memory in precocial birds. With the aim of elucidating of the neural basis for visual imprinting, we focused on visual information processing. RESULTS: A lesion in the visual wulst, which is similar functionally to the mammalian visual cortex, caused anterograde amnesia in visual imprinting behavior. Since the color of an object was one of the important cues for imprinting, we investigated color information processing in the visual wulst. Intrinsic optical signals from the visual wulst were detected in the early posthatch period and the peak regions of responses to red, green, and blue were spatially organized from the caudal to the nasal regions in dark-reared chicks. This spatial representation of color recognition showed plastic changes, and the response pattern along the antero-posterior axis of the visual wulst altered according to the color the chick was imprinted to. CONCLUSION: These results indicate that the thalamofugal pathway is critical for learning the imprinting stimulus and that the visual wulst shows learning-related plasticity and may relay processed visual information to indicate the color of the imprint stimulus to the memory storage region, e.g., the intermediate medial mesopallium

Chemosensitivity of Patient-Derived Cancer Stem Cells Identifies Colorectal Cancer Patients with Potential Benefit from FGFR Inhibitor Therapy

Some colorectal cancer patients harboring FGFR (fibroblast growth factor receptor) genetic alterations, such as copy number gain, mutation, and/or mRNA overexpression, were selected for enrollment in several recent clinical trials of FGFR inhibitor, because these genetic alterations were preclinically reported to be associated with FGFR inhibitor sensitivity as well as poor prognosis, invasiveness, and/or metastatic potential. However, few enrolled patients were responsive to FGFR inhibitors. Thus, practical strategies are eagerly awaited that can stratify patients for the subset that potentially responds to FGFR inhibitor chemotherapy. In the present study, we evaluated the sensitivity to FGFR inhibitor erdafitinib on 25 patient-derived tumor-initiating cell (TIC) spheroid lines carrying wild-type RAS and RAF genes, both in vitro and in vivo. Then, we assessed possible correlations between the sensitivity and the genetic/genomic data of the spheroid lines tested. Upon their exposure to erdafitinib, seven lines (7/25, 28%) responded significantly. Normal colonic epithelial stem cells were unaffected by the inhibitors. Moreover, the combination of erdafitinib with EGFR inhibitor erlotinib showed stronger growth inhibition than either drug alone, as efficacy was observed in 21 lines (84%) including 14 (56%) that were insensitive to erdafitinib alone. The in vitro erdafitinib response was accurately reflected on mouse xenografts of TIC spheroid lines. However, we found little correlation between their genetic/genomic alterations of TIC spheroids and the sensitivity to the FGFR inhibitor. Accordingly, we propose that direct testing of the patient-derived spheroids in vitro is one of the most reliable personalized methods in FGFR-inhibitor therapy of colorectal cancer patients

An improved method for culturing patient-derived colorectal cancer spheroids

患者由来大腸がん幹細胞培養を用いた薬剤感受性試験を開発 --個別化医療の実現へ期待--. 京都大学プレスリリース. 2018-09-03.Recent advances allowed culturing and examination of patient-derived colorectal cancer (PD-CRC) cells as organoids or spheroids. To be applied to practical personalized medicine, however, current methods still need to be strengthened for higher efficiency. Here we report an improved method to propagate PD-CRC tumor initiating cells (TICs) in spheroid culture. We established > 100 cancer spheroid lines derived from independent colorectal cancer patients employing a serum-containing medium with additional inhibitors, Y27632 and SB431542. Because colorectal cancer spheroids showed wide-range growth rates depending on the patient tumors, we searched for supplementary factors that accelerated proliferation of slow-growing CRC-TIC spheroids. To this end, we introduced a convenient growth-monitoring method using a luciferase reporter. We found that epidermal growth factor (EGF) and/or basic fibroblast growth factor (bFGF) were critical for steady propagation of a subset of CRC-TIC spheroids carrying the wild-type RAS and RAF genes. We also identified 5′-(N-ethyl-carboxamido)-adenosine (NECA), an adenosine receptor agonist, as an essential supplement for another subset of spheroids. Based on these results, we propose to optimize culture conditions for CRC-TIC spheroids by adjusting to the respective tumor samples. Our method provides a versatile tool that can be applied to personalized chemotherapy evaluation in prospective clinical studies

Transitional CP Violation in the MSSM and Electroweak Baryogenesis

Electroweak baryogenesis depends on the profile of the bubble wall created in the first-order phase transition. It is pointed out that CP violation in the Higgs sector of the MSSM could become large enough to explain the baryon asymmetry. We confirm this by solving the equations of motion for the Higgs fields with the effective potential at the transition temperature. That is, we present an example such that the transitional CP violation is realized and show the possibility that the baryon asymmetry of the universe may be produced, if marginally, by the $\tau$ lepton interacting with the wall, when an explicit CP breaking in the Higgs sector, which is consistent with experimental bounds, is induced at the phase transition.Comment: LaTeX2e, 18 pages with 7 eps files of figure

A human PSMB11 variant affects thymoproteasome processing and CD8+ T cell production

The Psmb11-encoded β5t subunit of the thymoproteasome, which is specifically expressed in cortical thymic epithelial cells (cTECs), is essential for the optimal positive selection of functionally competent CD8+ T cells in mice. Here, we report that a human genomic PSMB11 variation, which is detectable at an appreciable allele frequency in human populations, alters the β5t amino acid sequence that affects the processing of catalytically active β5t proteins. The introduction of this variation in the mouse genome revealed that the heterozygotes showed reduced β5t expression in cTECs and the homozygotes further exhibited reduction in the cellularity of CD8+ T cells. No severe health problems were noticed in many heterozygous and 5 homozygous human individuals. Long-term analysis of health status, particularly in the homozygotes, is expected to improve our understanding of the role of the thymoproteasome-dependent positive selection of CD8+ T cells in humans

Chemicals in the Environment and Brain Development: Importance of Neuroendocrinological Approaches

Mounting evidence shows that increasing numbers of children are being diagnosed with neurodevelopmental disorders, and it is clear that this increase cannot be explained by genetic background alone. A number of studies, including epidemiological studies, have found an association between in-utero and childhood exposure to certain chemicals, such as endocrine disruptors, psychoactive pharmaceuticals, volatile organic chemicals, persistent organic compounds and heavy metals, and children’s brain development. Yet, the mechanisms by which these chemicals impair brain development and function are not fully understood. In addition, little is known about how these chemicals enter and accumulate in the brain. Experimental approaches are essential to understand how those harmful chemicals enter children’s brain and pose discrete effects on specific brain sites. These approaches include the following: improvement of technologies for the detection and measurement of neuroendocrinological and behavioral changes in animal models: development of analytical methods for the identification and quantification of chemicals and their metabolites in the brain; development of in vitro cell line assays; and imaging technologies to illustrate cellular functions. In this research topic, we collected articles that provide state-of-the-art science and technologies that can help us identify environmental chemicals that influence brain development. We also included articles that lead to a better understanding of the actions and dynamics of these chemicals. The articles in this research topics supplied novel information about harmful endpoints of environmental chemicals. The reviews demonstrated the typical and novel interactions between environmental chemicals and the developing brain. We believe that these studies would lead to further understanding of neurodevelopmental disorders caused by environmental factors

Spatial partitioning between species of the phytoplankton-feeding guild on an estuarine intertidal sand flat and its implication on habitat carrying capacity

The fishery yield of Manila clams, Ruditapes philippinarum, increased considerably in the 1970s but has decreased rapidly since the middle 1980s on extensive intertidal sand flats in Ariake Sound (Kyushu, Japan). A survey conducted in 2004 on a 3.4-km2 sand flat located in the central part of the Sound (Shirakawa sand flat) revealed four dominant species: two thalassinidean shrimps (Upogebia majorand Nihonotrypaea japonica), which are deep-reaching burrow dwellers with strong bioturbation activities, and two bivalves (Mactra veneriformis and R. philippinarum). All four species belong to a phytoplankton (diatom)-feeding guild. In the late 1970s, the Manila clam population prevailed in high densities over the entire sand flat, whereas its distribution was restricted to the lowest quarter of the shore in 2004. In contrast, the population sizes and zones of occurrence of the other phytoplankton feeders have expanded in the absence of R. philippinarum, perhaps an indication of competitive release. After establishment, effects of the thalassinidean shrimps on sediment stability appear to have further reduced clam abundances. Across the sand flat in 2004, wet weight population biomass estimates for N. japonica, U. major, M. veneriformis, and R. philippinarum (whole body for shrimps and soft tissue for bivalves) were 304, 111, 378, and 234 tonnes, respectively. Based on Manila clam fishery yield records from Shirakawa, the carrying capacity of the Shirakawa sand flat in the late 1970s was estimated to be two times greater than the sum value for the whole phytoplankton-feeding guild in 2004. It is hypothesized that (1) the amount of phytoplankton determines the carrying capacity for the benthic community on the Shirakawa sand flat, with both phytoplankton and benthic biomass at maxima in the late 1970s, and (2) the subsequent increases in competition for space have caused further declines in the Manila clam population biomass to approximately one-eighth of its past value