Seasonal activity of the Japanese red-bellied newt, Cynops pyrrhogaster, was monitored in Minami-ohsawa, Hachioji-shi, Tokyo, from 2016 to 2017. The number of newts in the water of a pond was counted ...immediately after sunset, at least once a week, except in winter. The number of newts counted varied daily, and the time-series data on newt activity were analyzed using state-space modeling to estimate the impact of weather conditions and lunar phase on the activity due to the presence of plausible temporal autocorrelation. We found that some weather conditions, such as water temperature and atmospheric pressure, had significant positive effects on newt activity. Newts became more active during nights with higher temperatures and/or higher pressure. However, we did not detect any significant effect of the lunar phase on newt activity. The most important variable affecting newt activity was water temperature. The active season of newts was estimated to be nine months from March to November. Newt activity showed a sharp decline in the nightly activity of males and an extreme female-biased sex ratio was observed in early April suggesting that the degree of nocturnality differed across seasons and the two genders. This phenomenon may be related to the presence of mating activity during this particular season.
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FFLJ, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UL, UM, UPUK
In the mammalian circadian clockwork, CRY1 and CRY2 repressor proteins are regulated by posttranslational modifications for temporally coordinated transcription of clock genes. Previous studies ...revealed that FBXL3, an F-box-type E3 ligase, ubiquitinates CRYs and mediates their degradation. Here, we found that FBXL21 also ubiquitinates CRYs but counteracts FBXL3. Fbxl21−/− mice exhibited normal periodicity of wheel-running rhythms with compromised organization of daily activities, while an extremely long-period phenotype of Fbxl3−/− mice was attenuated in Fbxl3/Fbxl21 double-knockout mice. The double knockout destabilized the behavioral rhythms progressively and sometimes elicited arrhythmicity. Surprisingly, FBXL21 stabilized CRYs and antagonized the destabilizing action by FBXL3. Predominantly cytosolic distribution of FBXL21 contrasts with nuclear localization of FBXL3. These results emphasize the physiological importance of antagonizing actions between FBXL21 and FBXL3 on CRYs, and their combined actions at different subcellular locations stabilize oscillation of the circadian clock.
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► FBXL21 stabilizes CRY1 and CRY2, key players in the circadian clockwork ► FBXL21 action antagonizes the destabilizing action of FBXL3 on CRYs ► Depletion of Fbxl21/Fbxl 3 destabilized behavioral rhythm or caused arrhythmicity ► FBXL21 and FBXL3 actions are vital for robustness of the circadian clock oscillation.
FBXL21, an F-box-type ubiquitin E3 ligase, is identified as a regulator of the circadian clock repressor CRYPTOCHROME (CRY) proteins. FBXL21 has the opposite effects on circadian period and CRY stability compared to its homolog, FBXL3, and their combined actions at different subcellular locations ensures stable oscillation of the circadian clock.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We have investigated the calcite growth mechanism by directly imaging atomic-scale structural changes at the growing step edges with high-speed frequency modulation atomic force microscopy ...(HS-FM-AFM). We compared the results with those previously obtained during dissolution, where a transition region (TR) consisting of a Ca(OH)
2
monolayer was found to be formed along the step edges as an intermediate state. We found that the TR is created not only during dissolution but also during the growth process. Steps with and without a TR coexist with a ratio of 7 : 3 in both dissolution and growth, implying that their primary reaction pathways should involve TR formation. While all the dissolving steps show a linear shape, the growing steps additionally present a complex non-linear shape with many kinks. The TRs formed along the linear steps present a fixed and uniform width, while those along the complex steps present a non-uniform and dynamically varying width. The acute and obtuse steps show similar TR formation probability, TR width, and step velocity during growth, while a TR is preferentially formed along an acute step during dissolution. For both step types, TRs during growth are wider than those during dissolution. Based on these findings, we present possible reaction pathways triggered by the adsorption of either CO
2
or HCO
3
−
for the elementary steps in calcite growth.
We have investigated the calcite growth mechanism by directly imaging atomic-scale structural changes at the growing step edges with high-speed frequency modulation atomic force microscopy (HS-FM-AFM).
Patient-derived xenograft (PDX) murine models are employed for preclinical research on cancers, including non-small cell lung cancers (NSCLCs). Even though lung squamous cell carcinomas (LUSCs) show ...the highest engraftment rate among NSCLCs, half of them nevertheless show PDX failure in immunodeficient mice. Here, using immunohistochemistry and RNA sequencing, we evaluated the distinct immunohistochemical and gene expression profiles of resected LUSCs that showed successful engraftment. Among various LUSCs, including the basal, classical, secretory, and primitive subtypes, those in the non-engrafting (NEG) group showed gene expression profiles similar to the pure secretory subtype with positivity for CK7, whereas those in the engrafting (EG) group were similar to the mixed secretory subtype with positivity for p63. Pathway analysis of 295 genes that demonstrated significant differences in expression between NEG and EG tumors revealed that the former had enriched expression of genes related to the immune system, whereas the latter had enriched expression of genes related to the cell cycle and DNA replication. Interestingly, NEG tumors showed higher infiltration of B cells (CD19+) and follicular dendritic cells (CD23+) in lymph follicles than EG tumors. Taken together, these findings suggest that the PDX cancer model of LUSC represents only a certain population of LUSCs and that CD19- and CD23-positive tumor-infiltrating immune cells in the original tumors may negatively influence PDX engraftment in immunodeficient mice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Angioimmunoblastic T-cell lymphoma (AITL) is an intractable type of T-cell lymphoma. We and others have identified that the p.Gly17Val RHOA mutation is specifically identified in AITL. We herein ...report a patient whose condition deteriorated, resulting from massive pericardial effusion one month after undergoing autologous transplantation for AITL. He was diagnosed with cardiac tamponade caused by AITL recurrence in the presence of the p.Gly17Val RHOA mutation as well as T-lineage cells with an aberrant immune-phenotype in the pericardial effusion. This case suggests that a precision medicine approach by detecting the presence of a p.Gly17Val RHOA mutation is useful for the management of AITL.
Sternal bone fractures with bilateral multiple rib fractures cause serious instability of the anterior chest wall, and prolonged mechanical ventilation may be required. A 45-year-old man was injured ...in a motor vehicle collision. He suffered from a bilateral flail chest injury accompanied by a transverse sternal fracture. Minimally invasive surgical stabilisation of the anterior chest wall was performed using two bars as per the Nuss procedure. Two days after surgery, he was extubated from artificial respiration and was ultimately discharged without any complications.
Differential resource use allows for diverse species to specialize in ecological niches and thus coexist in a particular area. In the Japanese archipelago, increasing sika deer (
, Temminck 1836) ...densities have excluded the Japanese serow (
, Temminck 1836), but in places where deer population densities are low, the two species coexist. We wanted to better understand their habitats and how these two ungulates manage to coexist. We evaluated the role of habitat use in the coexistence of these two sympatric ungulates on Mt. Asama, central Japan. Deer frequently used the dwarf bamboo-rich communities in autumn and winter, and their habitat use was not associated with topography. Serows frequently used deciduous broadleaf shrub-rich communities and steep slopes throughout the year. Consequently, their habitat use was significantly different in terms of vegetation and topography. Niche breadth suggests that deer tend to be generalists, whereas serows tend to be specialists. Niche differentiation in habitat use between deer and serows may make the coexistence of these similarly sized ungulates possible in Japanese mountainous zones. Therefore, the fine-grained habitat mosaic of different vegetation and topography areas might be the underlying feature that allows the coexistence of these two species.
A 54-year-old woman with adenocarcinoma of the lung and lymph node metastasis experienced nystagmus and cerebellar ataxia 2 weeks after initiating nivolumab therapy. An evaluation for several ...autoimmune-related antibodies and paraneoplastic syndrome yielded negative results. We eventually diagnosed the patient with nivolumab-induced acute cerebellar ataxia, after excluding other potential conditions. Her ataxic gait and nystagmus resolved shortly after intravenous steroid pulse therapy followed by the administration of decreasing doses of oral steroids. Nivolumab, an immune checkpoint inhibitor, is known to induce various neurological adverse events. However, this is the first report of acute cerebellar ataxia associated with nivolumab treatment.
The response of cells to environmental stimuli, under either physiological or pathological conditions, plays a key role in determining cell fate toward either adaptive survival or controlled death. ...The efficiency of such a feedback mechanism is closely related to the most challenging human diseases, including cancer. Since cellular responses are implemented through physical forces exerted on intracellular components, more detailed knowledge of force distribution through modern imaging techniques is needed to ensure a mechanistic understanding of these forces. In this work, we mapped these intracellular forces at a whole-cell scale and with submicron resolution to correlate intracellular force distribution to the cytoskeletal structures. Furthermore, we visualized dynamic mechanical responses of the cells adapting to environmental modulations in situ. Such task was achieved by using an informatics-assisted atomic force microscope (AFM) indentation technique where a key step was Markov-chain Monte Carlo optimization to search for both the models used to fit indentation force–displacement curves and probe geometry descriptors. We demonstrated force dynamics within cytoskeleton, as well as nucleoskeleton in living cells which were subjected to mechanical state modulation: myosin motor inhibition, micro-compression stimulation and geometrical confinement manipulation. Our results highlight the alteration in the intracellular prestress to attenuate environmental stimuli; to involve in cellular survival against mechanical signal-initiated death during cancer growth and metastasis; and to initiate cell migration.