HIPPOはカバという意味ですが、もともとはショウジョウバエの突然変異体の表現型に対して付けられた名前です。組織の細胞増殖が制御不能になってデカくなってしまったことを描写した名前のようです。哺乳類のオルソログ遺伝子MST1/2の働きを肝臓において破壊してやると(conditional knock out mice)、肝臓がデカくなります。つまり、肝臓においては、肝臓の細胞の増殖を制御しているということがわかります。おそらく、全身でノックアウトすると多分致死なので、コンディショナルノックアウトマウスを作って表現型を調べたのでしょう。
Development 138, 9-22 (2011) doi:10.1242/dev.045500 Hippo signaling: growth control and beyond
Mst1 and Mst2 are 56–60kDa class 2 GC kinases that share 76% identity in amino acid sequence (Dan et al., 2001).
Mst1/2 are the closest mammalian homologs of the Drosophila Hippo kinase.
Loss of Hippo function (in the fly eye) results in massive overgrowth, due to an acceleration of cell cycle progression and a failure of developmental apoptosis (Harvey et al., 2003; Udan et al., 2003; Wu et al., 2003);
Hippo, when bound to the adaptor protein Salvador/Shar-pei, phosphorylates the Lats/Warts kinase.
Hippo also phosphorylates the noncatalytic polypeptide, Mats (Mob1 as tumor Suppressor), enabling the latter to promote Lats/Warts autophosphorylation and activation.
Active Lats/Warts in turn phosphorylates and inhibits the transcriptional coregulator Yorkie, by promoting its binding to 14-3-3 and nuclear exit (Dong et al., 2007).
The regulation of Hippo kinase activity is less well defined, although elimination of the atypical cadherin, Fat, or both of the FERM domain proteins, Merlin and Expanded, results in Yorkie-dependent phenotypes resembling Hippo loss of function (Reddy and Irvine, 2008).
cell-cell contact of cultured mammalian cells induces phosphorylation and inactivation of Yap1, whereas overexpression of Yap1 or inactivation of either Lats2 or NF2/Merlin bypasses contact inhibition of growth (McPherson et al., 2004; Morrison et al., 2001; Zhao et al., 2007).
mouse keratinocytes lacking WW45, the ortholog of Salvador/Shar-pei, fail to activate Mst1, phosphorylate Yap1, and exit the cell cycle during differentiation in vitro (Lee et al., 2008).
Mst1 deficient mice exhibit greatly diminished numbers of mature, naïve T cells in peripheral lymphoid organs associated with defects in adhesion and migration of the Mst1 null T cells.
In mammalian cells, MST1/2 (Hippo orthologues) can be activated by several membrane receptors and subsequently phosphorylate downstream kinases LATS1/2 (Warts orthologues) in events that are coordinated by scaffold proteins MOB1 (Mats orthologue) and WW45 (Salvador orthologue) (16, 17). Activated LATS1/2 can directly phosphorylate YAP1 (Yorkie orthologue) at Ser127, which provides a docking site for 14-3-3 protein and then leads to YAP1 cytoplasmic retention (18). Phosphorylated YAP1 also recruits Skp1/Cul1/F-box protein (SCF)–β-transducing repeat containing protein (β-TRCP) E3 ligase which
promotes YAP1 ubiquitination and degradation in the cytoplasm (19). When YAP1 is in the nucleus, YAP1 binds to transcription factors such as TEA domain transcription factor (TEAD) and activates the transcription of proliferation and/or survival-related genes (20).
dysregulation of YAP1 greatly enhances tumorigenesis because YAP1 not only promotes cell proliferation but also leads to epithelial-mesenchymal transition (EMT),3 which lessens cell contact inhibition and thus allows tumorigenesis (18, 21).
When the Hippo pathway is turned on, MST1/2 is phosphorylated and form a complex with SAV1, which phosphorylates and activates the LATS1/2-MOB1 complex. This activated complex then phosphorylates YAP/TAZ resulting in either degradation or cytoplasmic retention leading to reduced nuclear YAP/TAZ levels and down regulation of the downstream targets of this pathway.
During the off-state of the Hippo signaling pathway, unphosphorylated YAP/TAZ translocate to the nucleus and form a complex with TEA domain proteins 1-4 (TEAD1-4) promoting gene expression involved in cell survival, proliferation, and migration.
MST1/MST2 (Mammalian homologues of Drosophila Hippo)
The Drosophila Mst Ortholog, hippo, Restricts Growth and Cell Proliferation and Promotes Apoptosis Cell Volume 114, Issue 4 , 22 August 2003, Pages 457-467 Here, we describe mutations in hippo (hpo), which encodes a protein kinase most related to mammalian Mst1 and Mst2. Like wts and sav, hpo mutations result in increased tissue growth and impaired apoptosis characterized by elevated levels of the cell cycle regulator cyclin E and apoptosis inhibitor DIAP1. HIPPOを同定した論文！哺乳類のホモログはすでに知られていたのですね。サイクリンEはG1期からS期へ移行するときに必要な分子です。
The FERM domain proteins Merlin (Mer) and Expanded (Ex) are upstream components that regulate Hpo activity through unknown mechanisms. Here we identify Kibra as another upstream component of the Hippo signaling pathway. We show that Kibra functions together with Mer and Ex in a protein complex localized to the apical domain of epithelial cells, and that this protein complex regulates the Hippo kinase cascade via direct binding to Hpo and Sav.
Kibra Functions as a Tumor Suppressor Protein that Regulates Hippo Signaling in Conjunction with Merlin and Expanded Developmental Cell 18, 288–299, February 16, 2010 https://www.cell.com/developmental-cell/pdf/S1534-5807(10)00006-7.pdf
We propose that both Hippo pathway-dependent and Hippo pathway-independent mechanisms regulate Yap localization to set apart pluripotent and differentiated lineages in the pre-implantation mouse embryo.
Leung, C., Zernicka-Goetz, M. Angiomotin prevents pluripotent lineage differentiation in mouse embryos via Hippo pathway-dependent and -independent mechanisms.Nat Commun4, 2251 (2013). https://doi.org/10.1038/ncomms3251 https://www.nature.com/articles/ncomms3251
YAP may also be repressed in a phosphorylation-independent manner
in Drosophila (22). In this case, the Hippo pathway components Expanded, Hippo, and Warts can directly bind to YAP1 through physical interaction between their corresponding PY motifs and the WW domains of YAP1.
Here, we report the identification of angiomotin (AMOT) and angiomotin-like proteins as new YAP1-associated proteins. AMOT is a vascular angiogenesis-related protein, which was initially identified as an angiogenesis inhibitor angiostatin-binding protein through a yeast twohybrid screen (23, 24).
There are two other angiomotin-like proteins, AMOTL1 and AMOTL2. These three proteins belong to a new protein family with a highly conserved coil-coil domain, PDZ binding domain, and glutamine-rich domain (24).
AMOT, AMOTL1, and AMOTL2 specifically interact with YAP1. This interaction is important for the regulation of YAP1 cytoplasm-to-nucleus translocation. Just like YAP1 overexpression, down-regulation of AMOTL2 in MCF10A cells promotes EMT. Together, these data suggest that YAP1 is regulated in vivo via its directinteractions with angiomotin-like proteins.
The Angiomotins – From discovery to function FEBS Letters Volume 588, Issue 16 , 19 August 2014, Pages 2693-2703 https://www.sciencedirect.com/science/article/pii/S0014579314001252
Annu Rev Genet. Author manuscript; available in PMC 2019 Nov 23. Published in final edited form as: Annu Rev Genet. 2018 Nov 23; 52: 65–87. Published online 2018 Sep 5. doi: 10.1146/annurev-genet-120417-031621 PMCID: PMC6322405 NIHMSID: NIHMS1002595 PMID: 30183404 The Hippo signaling network and its biological functions
Investigating the role of the Hippo pathway member Nf2 in the segregation of trophectoderm and inner cell mass Katie Cockburn Published 1 November 2015 https://www.semanticscholar.org/paper/Investigating-the-role-of-the-Hippo-pathway-member-Cockburn/426d8e88f606c02cd4df88bc2a4006b7d42b5b61/figure/3
Overview of junctional complexes during mammalian early embryonic development Frontiers Frontiers in Endocrinology 14 DOI:10.3389/fendo.2023.1150017 https://www.researchgate.net/figure/Differential-modulation-of-the-Hippo-signaling-pathway-in-inner-and-outer-cells-of-the_fig3_370168194
Emerging roles for angiomotin in the nervous system Science Signaling 27 Oct 2020 Vol 13, Issue 655 DOI: 10.1126/scisignal.abc0635 https://www.science.org/doi/10.1126/scisignal.abc0635
2015年の論文ですが、一番網羅的な図は下の図でしょうか。
DOI:10.1093/abbs/gmu110Corpus ID: 24216059 The regulation and function of YAP transcription co-activator. Chu Zhu, Li Li, Bin Zhao Published in Acta Biochimica et Biophysica… 2015 Biology, Medicine https://www.semanticscholar.org/paper/The-regulation-and-function-of-YAP-transcription-Zhu-Li/1f32caa888a61e0717a5b20d0699d971e1933d17
質問 Strange enough, E-Cadherin acts during compaction. How you can consolidate the two facts: E-cadherin is nessary compaction in the outer cells, whereas E-cadherin is necessary for HIPPO activation in inner cells?
Perplexityの回答
Based on the search results and the information provided, we can consolidate the seemingly contradictory roles of E-cadherin in outer and inner cells during early embryo development as follows:
Role in outer cells during compaction:
E-cadherin is crucial for the compaction process in outer cells of the early embryo. It mediates cell-cell adhesion, which is essential for the morphological changes that occur during compaction.
Expression of e-cadherin in early mouse embryo development Vet Hekim Der Derg 91 (1): 9-14, 2020 https://dergipark.org.tr/tr/download/article-file/925118
Cell adhesion in the preimplantation mammalian embryo and its role in trophectoderm differentiation and blastocyst morphogenesis Front Biosci . 2001 Aug 1:6:D1000-7. doi: 10.2741/fleming. https://pubmed.ncbi.nlm.nih.gov/11487467/
E-cadherin localizes to cell-cell contact regions in outer cells, helping to establish the initial polarization of these cells.
PLoS One. 2019; 14(2): e0212109. Published online 2019 Feb 8. doi: 10.1371/journal.pone.0212109 PMCID: PMC6368326 PMID: 30735538 No evidence of involvement of E-cadherin in cell fate specification or the segregation of Epi and PrE in mouse blastocysts
Overview of junctional complexes during mammalian early embryonic development Front. Endocrinol., 20 April 2023 Sec. Experimental Endocrinology Volume 14 – 2023 | https://doi.org/10.3389/fendo.2023.1150017
Role in inner cells and Hippo pathway activation:
In inner cells, E-cadherin plays a different role. It is involved in activating the Hippo signaling pathway, which is crucial for cell fate determination.
Mol Hum Reprod. 2016 Oct; 22(10): 691–703. Published online 2016 Oct 5. doi: 10.1093/molehr/gav068 PMCID: PMC5062000 PMID: 26660321 Polarity and cell division orientation in the cleavage embryo: from worm to human
The extensive cell-cell contacts mediated by E-cadherin in inner cells lead to the activation of Hippo pathway kinases.
Front. Endocrinol., 20 April 2023 Sec. Experimental Endocrinology Volume 14 – 2023 | https://doi.org/10.3389/fendo.2023.1150017 Overview of junctional complexes during mammalian early embryonic development
To consolidate these two facts, we can understand that:
a) E-cadherin’s function is context-dependent: Its role differs based on the cell’s position within the embryo (outer vs. inner).
b) Differential distribution: In outer cells, E-cadherin is redistributed during compaction, becoming concentrated at cell-cell contact sites but removed from the apical membrane domain. In inner cells, E-cadherin is more evenly distributed along the cell membrane.
c) Interaction with other factors: E-cadherin cooperates with other molecules like angiomotin (Amot) and the Par-aPKC system to establish polarity in outer cells and activate Hippo signaling in inner cells.
The E-cadherin/AmotL2 complex organizes actin filaments required for epithelial hexagonal packing and blastocyst hatchingScientific Reports volume 7, Article number: 9540 (2017). “and mammalian trophectoderm in vivo. We show that amotL2 is a component of the E-cadherin complex that is essential for the formation of radial actin filaments. Functionally, depletion of amotL2 and subsequent loss of radial actin fibers resulted in stalled hatching of mouse and human embryos from the zona pellucida.” https://www.nature.com/articles/s41598-017-10102-w AmotL2 (angiomotin-like 2) forms a complex with E-cadherin. This complex associates with radial actin filaments connecting cells over multiple layers. The paper shows that AmotL2 is part of the E-cadherin junctional protein complex. Co-immunoprecipitation analysis demonstrated that AmotL2 was directly or indirectly bound to E-cadherin as well as α and β-catenin.
d) Mechanical forces: The different mechanical environments of outer and inner cells may influence how E-cadherin-mediated adhesion translates into signaling outcomes.
Dual role of E-cadherin in cancer cells Tissue Barriers Volume 10, 2022 – Issue 4 Submit an article Journal https://www.tandfonline.com/doi/full/10.1080/21688370.2021.2005420
e) Temporal aspects: E-cadherin’s role evolves as development progresses. It first mediates compaction, then contributes to establishing and maintaining the distinct fates of outer (trophectoderm) and inner (inner cell mass) cells.
Gene replacement reveals a specific role for E-cadherin in the formation of a functional trophectoderm 01 January 2007 Development https://journals.biologists.com/dev/article/134/1/31/52730/Gene-replacement-reveals-a-specific-role-for-E
In summary, E-cadherin plays a dual role: it is necessary for compaction in outer cells while also being crucial for Hippo pathway activation in inner cells. This dual function is achieved through differential localization, interaction with other proteins, and the distinct microenvironments of outer and inner cells in the early embryo.
Based on the recent literature, there have been several advancements in biomarkers for psychological stress:
1. Cortisol remains a key biomarker, with new developments in detection methods:
– Wearable, flexible devices for real-time, continuous cortisol monitoring in sweat have been developed[6].
– Electrochemical biosensors enable rapid, real-time detection of cortisol in biofluids[8].
– Salivary cortisol sensing is being integrated into smart dentures and braces for ambulatory monitoring[7].
2. Multi-biomarker approaches:
– Allostatic load, which measures cumulative biological burden across multiple systems, is being used as a comprehensive stress biomarker[5].
– Combinations of biomarkers like cortisol, α-amylase, chromogranin A, brain-derived neurotrophic factor, and immunoglobulin A in saliva are being studied[7].
3. Genetic and molecular biomarkers:
– FKBP5 gene expression has emerged as a top biomarker for stress disorders[1].
– MicroRNAs and long non-coding RNAs are being explored as potential stress biomarkers[2].
4. Immune system markers:
– C-reactive protein (CRP) and interleukins 6 and 8 have shown promise as diagnostic biomarkers of chronic stress[3].
– Changes in natural killer (NK) cell activity are being investigated[3].
5. Metabolic biomarkers:
– Glucose, HbA1c, triglycerides, and cholesterol levels are being studied in relation to chronic stress[3].
6. Oxidative stress markers:
– Malondialdehyde and isoprostanes are being examined as indicators of stress-induced oxidative damage[2].
7. Advanced detection technologies:
– Surface plasmon resonance sensing and molecular imprinted polymers offer sensitive cortisol detection[7].
– Integration of aptamers with electrochemiluminescence biosensing provides label-free, cost-effective approaches[7].
These advancements are moving towards more comprehensive, real-time, and non-invasive methods of stress assessment, with potential applications in personalized stress management and health monitoring.
Based on the search results, here are some relevant review articles on biomarkers for psychological stress from Cell Press journals:
## Neuron: A Neural Biomarker of Psychological Vulnerability to Future Life Stress
This study demonstrated that individual differences in threat-related amygdala reactivity can predict psychological vulnerability to life stress occurring 1 to 4 years in the future[6]. The researchers found that heightened amygdala reactivity to threat was associated with greater susceptibility to stress-related mental health problems like depression and anxiety when exposed to major life stressors. This suggests amygdala reactivity could serve as a neural biomarker to identify those at higher risk of developing stress-related psychopathology.
## Immunity: The Gut Microbiome Regulates Psychological-Stress-Induced Inflammation
This review article explored how psychological stress impacts inflammation through interactions with the gut microbiome[7]. The researchers found that stress promotes vascular occlusive events (VOEs) by eliciting a glucocorticoid hormonal response that increases gut permeability. This leads to microbiota-dependent interleukin production, highlighting the gut microbiome’s role in mediating stress-induced inflammatory responses. The findings suggest gut microbiome composition and function could potentially serve as biomarkers of stress vulnerability.
## Key Points:
– Threat-related amygdala reactivity may predict future stress vulnerability
– Gut microbiome regulates stress-induced inflammation
– Stress increases gut permeability and microbiota-dependent cytokine production
– Gut microbiome markers could indicate stress susceptibility
These Cell Press reviews provide insight into both neural and gut microbiome-based biomarkers that may help identify individuals at higher risk of adverse health effects from psychological stress. The findings point to promising avenues for developing predictive biomarkers of stress vulnerability, which could enable earlier interventions for at-risk individuals.
Giannakakis, G., Grigoriadis, D., Giannakaki, K., Simantiraki, O., Roniotis, A., & Tsiknakis, M. (2019). Review on Psychological Stress Detection Using Biosignals. IEEE Transactions on Affective Computing, 13, 440-460. https://doi.org/10.1109/TAFFC.2019.2927337. Psychological stress is effectively detected using biosignals, with this paper providing guidelines for efficient detection and enhancing the reliability of biosignal data features.
Chojnowska, S., Ptaszyńska-Sarosiek, I., Kępka, A., Knaś, M., & Waszkiewicz, N. (2021). Salivary Biomarkers of Stress, Anxiety and Depression. Journal of Clinical Medicine, 10. https://doi.org/10.3390/jcm10030517. Salivary biomarkers, such as cortisol, lysozyme, sAA, and CgA, show promise in quick diagnosis and monitoring of stress, anxiety, and depression, potentially aiding in pharmacological treatment monitoring.
Dhama, K., Latheef, S., Dadar, M., Samad, H., Munjal, A., Khandia, R., Karthik, K., Tiwari, R., Yatoo, M., Bhatt, P., Chakraborty, S., Singh, K., Iqbal, H., Chaicumpa, W., & Joshi, S. (2019). Biomarkers in Stress Related Diseases/Disorders: Diagnostic, Prognostic, and Therapeutic Values. Frontiers in Molecular Biosciences, 6. https://doi.org/10.3389/fmolb.2019.00091. Stress biomarkers can help monitor stress levels, aid in prognosis, and guide therapy for stress-related diseases and disorders.
Le-Niculescu, H., Roseberry, K., Levey, D., Rogers, J., Kosary, K., Prabha, S., Jones, T., Judd, S., McCormick, M., Wessel, A., Williams, A., Phalen, P., Mamdani, F., Sequeira, A., Kurian, S., & Niculescu, A. (2019). Towards precision medicine for stress disorders: diagnostic biomarkers and targeted drugs. Molecular Psychiatry, 25, 918 – 938. https://doi.org/10.1038/s41380-019-0370-z. This study identified blood gene expression biomarkers that can predict psychological stress and future psychiatric hospitalizations, potentially improving diagnosis and treatment for stress disorders like PTSD.
An, K., Salyer, J., Brown, R., Kao, H., Starkweather, A., & Shim, I. (2016). Salivary Biomarkers of Chronic Psychosocial Stress and CVD Risks. Biological Research For Nursing, 18, 241 – 263. https://doi.org/10.1177/1099800415604437. Salivary biomarkers, particularly cortisol, have been useful in stress research, particularly when linked to cardiovascular disease risks.
McEwen, B. (2015). Biomarkers for assessing population and individual health and disease related to stress and adaptation.. Metabolism: clinical and experimental, 64 3 Suppl 1, S2-S10 . https://doi.org/10.1016/j.metabol.2014.10.029. Biomarkers play a crucial role in stress biology, assessing individual and population health and predicting disease risk, with potential for predictive biomarkers for suicidal depression.
Labad, J., Stojanovic-Pérez, A., Montalvo, I., Solé, M., Cabezas, Á., Ortega, L., Moreno, I., Vilella, E., Martorell, L., Reynolds, R., & Gutiérrez-Zotes, A. (2015). Corrigendum to “Stress biomarkers as predictors of transition to psychosis in at-risk mental states: Roles for cortisol, prolactin and albumin” [J. Psychiatr. Res. 60 (2015) 163–169]. Journal of Psychiatric Research, 62, 138. https://doi.org/10.1016/J.JPSYCHIRES.2015.01.012. Cortisol, prolactin, and albumin are key stress biomarkers that predict the transition to psychosis in at-risk mental states.
Labad, J., Stojanovic-Pérez, A., Montalvo, I., Solé, M., Cabezas, Á., Ortega, L., Moreno, I., Vilella, E., Martorell, L., Reynolds, R., & Gutiérrez-Zotes, A. (2015). Stress biomarkers as predictors of transition to psychosis in at-risk mental states: roles for cortisol, prolactin and albumin.. Journal of psychiatric research, 60, 163-9 . https://doi.org/10.1016/j.jpsychires.2014.10.011. Prolactin levels are a predictor of psychosis transition in individuals with at-risk mental states, while albumin levels have a protective effect.
Batista, P., Pereira, A., & Vaz, A. (2017). Salivary Biomarkers in Psychological Stress Diagnosis. , 3, 9-18. https://doi.org/10.20431/2455-1538.0302002. Salivary cortisol and alpha-amylase biomarkers are the most used in diagnosing psychological stress, providing valuable information for understanding diseases and their responses to treatment.
Ockenburg, S., Booij, S., Riese, H., Rosmalen, J., & Janssens, K. (2015). How to assess stress biomarkers for idiographic research?. Psychoneuroendocrinology, 62, 189-199. https://doi.org/10.1016/j.psyneuen.2015.08.002. Idiographic research, using various matrices and new collection tools, can provide promising new insights into the association between stress biomarkers and psychological or somatic symptoms.
Indexes for psysiological and sociopsychological assessments of mental stress experienced by pregnant women: A literature review. M TSUBAKI, K KABEYAMA
Hippo Signal Pathway Creative BioMart チャンネル登録者数 3220人 チャンネル登録
HIPPO（カバの意味）の役割は増殖を止めることだそうです。
Hippo Signaling Regulates Microprocessor and Links Cell-Density-Dependent miRNA Biogenesis to Cancer Cell Press チャンネル登録者数 2.55万人
もともとの発見は、ショウジョウバエで組織の細胞増殖に異常を示す突然変異体として同定されました。
Sci Rep. 2020; 10: 3173. Published online 2020 Feb 21. doi: 10.1038/s41598-020-60120-4 PMCID: PMC7035326 PMID: 32081887 Systematic analysis of the Hippo pathway organization and oncogenic alteration in evolution
The discovery and expansion of Hippo signaling pathway in Drosophila model July 2017Hereditas (Beijing) 39(7):537-545 39(7):537-545 DOI:10.16288/j.yczz.17-051 https://www.researchgate.net/publication/320893314_The_discovery_and_expansion_of_Hippo_signaling_pathway_in_Drosophila_model 本文は中国語？ The discovery of Hippo signaling pathway is another breakthrough of fly genetics. Similar to the other signaling pathways, Hippo pathway also functions crucially in tremendous physiological and pathological conditions, like organ size control and cancer. There are three main stages of Hippo pathway study: Firstly, identifications of core components by fly genetic screens; secondly, regulations by versatile upstream cues, like cytoskeleton, mechanical tension, and nutrition
HIPPOシグナリングを構成するシグナル分子
In mammals, the Hippo pathway is composed of several key components, including mammalian STE20-like kinase 1/2 (MST1/2), protein Salvador homologue 1 (SAV1), MOBKL1A/B (MOB1A/B), large tumour suppressor kinase 1/2 (LATS1/2), Yes-associated protein 1 (YAP), WW-domain-containing transcription regulator 1 (TAZ), and the transcriptional enhanced associated domain (TEAD) family1 (Fig. 2). YAP/TAZ are transcriptional coactivators that bind to TEAD1–4 to regulate the expression of a wide array of genes that mediate cell proliferation, apoptosis, and stem cell self-renewal.2 Moreover, a variety of upstream signals, such as cell polarity, mechanical cues, cell density, soluble factors and stress signals, modulate the Hippo pathway.3,4,5
08 November 2022 The Hippo signalling pathway and its implications in human health and diseases https://www.nature.com/articles/s41392-022-01191-9 オープンアクセス論文
The central core of this pathway includes a pair of kinases, Hippo and Warts (Wts), which act in sequence to phosphorylate the transcriptional co-activator Yorkie (Yki) (Huang et al., 2005). Phosphorylation of Yki by Wts promotes cytoplasmic localization of Yki, thus reducing Yki-dependent transcription and growth (Dong et al., 2007; Oh and Irvine, 2008). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215397/
The mammalian Hippo pathway is more complicated than the Drosophila Hippo pathway. One of the reasons for this complexity is that mammals have more than one paralogue for each Drosophila component. These paralogues sometimes play redundant roles but in most cases exhibit distinct properties. Second and more importantly, the components of the mammalian Hippo pathway undergo many molecular interactions, so they exert additional functions and are subject to additional regulation. For instance, the substrates of MST kinases include not only LATS kinases and MOB1, but also c-Jun N-terminal kinase (JNK), histone H2B and FoxO, as discussed below (85,86). All of them are implicated in apoptosis. LATS1 interacts with LIM domain kinase 1 to inhibit its kinase activity and thereby affects cytokinesis (87). It also binds mitochondrial serine protease Omi/HtrA2 to promote the protease activity (88,89). Omi/HtrA2 controls cell proliferation through LATS1. If we define the final outputs of the Hippo pathway as the regulation of cell proliferation and cell death, it can be argued that these molecular interactions also mediate Hippo signalling. No matter how we demarcate the Hippo pathway, we need to consider that activation of the MST–LATS–YAP/TAZ axis is associated with parallel activation of other pathways, which co-operate with the canonical Hippo pathway. https://academic.oup.com/jb/article/149/4/361/968447
Possible pathway initiating the distinction between inner cell mass and trophoblast Bio peak チャンネル登録者数 2480人 https://www.youtube.com/watch?v=bwcICTcF2wE
Valham, F., Sahlin, C., Stenlund, H., & Franklin, K. (2012). Ambient temperature and obstructive sleep apnea: effects on sleep, sleep apnea, and morning alertness.. Sleep, 35 4, 513-7 . https://doi.org/10.5665/sleep.1736. 室温が 16°C の場合、24°C の場合と比較して総睡眠時間が平均 30 分長くなり、患者の朝の覚醒状態も向上しました。
室温が低いほど、睡眠効率が高く、総睡眠時間が長くなる傾向がある。
Raj, A., Ruder, M., Rus, H., Gahan, L., O’Mullane, B., Danoff-Burg, S., & Raymann, R. (2020). 1214 Higher Bedroom Temperature Associated With Poorer Sleep: Data From Over 3.75 Million Nights. Sleep, 43. https://doi.org/10.1093/sleep/zsaa056.1208. 寝室の温度が高いと、睡眠の質が低下し、覚醒時間が長くなります。
Raj, A., Ruder, M., Rus, H., Gahan, L., O’Mullane, B., Danoff-Burg, S., & Raymann, R. (2020). 1214 Higher Bedroom Temperature Associated With Poorer Sleep: Data From Over 3.75 Million Nights. Sleep, 43. https://doi.org/10.1093/sleep/zsaa056.1208. 寝室の温度が高いと、睡眠の質が低下し、覚醒時間が長くなります。
高温環境では、深い睡眠時間が短くなり、睡眠の質が低下する。
Bischof, W., Madsen, T., Clausen, J., Madsen, P., & Wildschi∅dtz, G. (1991). Sleep and the temperature field of the bed. Journal of Thermal Biology, 18, 393-398. https://doi.org/10.1016/0306-4565(93)90064-Z. ベッド内の温度の変動が大きいほど、深い眠りの時間が短くなります。
Teramoto, Y., Tokura, H., Ioki, I., Suho, S., Inoshiri, R., & Masuda, M. (1998). THE EFFECT OF ROOM TEMPERATURE ON RECTAL TEMPERATURE DURING NIGHT SLEEP. Journal of Thermal Biology, 23, 15-21. https://doi.org/10.1016/S0306-4565(97)00041-7. Fall-Rise 室温設定では、深部体温がより深く下がり、主観的な睡眠感覚も向上しました。
夕方から朝にかけての温度変動がある環境では、睡眠の質が向上し、朝の覚醒感が良くなる。
Kondo, M., Tokura, H., Wakamura, T., Hyun, K., Tamotsu, S., Morita, T., & Oishi, T. (2007). Physiological significance of cyclic changes in room temperature around dusk and dawn for circadian rhythms of core and skin temperature, urinary 6-hydroxymelatonin sulfate, and waking sensation just after rising.. Journal of physiological anthropology, 26 4, 429-36 . https://doi.org/10.2114/JPA2.26.429.夕暮れと夜明けの室温の周期的な変化は、より深い睡眠と起床直後のより良い目覚めを促進します。
温度と睡眠段階の関係:
室温が高いと、睡眠効率とREM睡眠の割合が低下する。
Xiong, J., Lan, L., Lian, Z., & Dear, R. (2020). Associations of bedroom temperature and ventilation with sleep quality. Science and Technology for the Built Environment, 26, 1274 – 1284. https://doi.org/10.1080/23744731.2020.1756664.寝室の動作温度が上昇すると、睡眠効率とレム睡眠の割合が減少します。
温度が適切でないと、深い睡眠時間が短くなる。
Bischof, W., Madsen, T., Clausen, J., Madsen, P., & Wildschi∅dtz, G. (1991). Sleep and the temperature field of the bed. Journal of Thermal Biology, 18, 393-398. https://doi.org/10.1016/0306-4565(93)90064-Z.ベッド内の温度の変動が大きいほど、深い眠りの時間が短くなります。
Obradovich, N., Migliorini, R., Mednick, S., & Fowler, J. (2017). Nighttime temperature and human sleep loss in a changing climate. Science Advances, 3. https://doi.org/10.1126/sciadv.1601555.夜間の気温の上昇により、睡眠不足の夜の自己申告が増加し、その影響は夏季に最も大きく、低所得層および高齢者層で顕著に表れています。
Fan, Y., Wang, Y., Gu, P., Han, J., & Tian, Y. (2022). How Temperature Influences Sleep. International Journal of Molecular Sciences, 23. https://doi.org/10.3390/ijms232012191.温度は睡眠の調節に重要な役割を果たしており、その影響を理解することで睡眠障害を管理するための戦略を立てることができます。
Zhang, X., Luo, G., Xie, J., & Liu, J. (2021). Associations of bedroom air temperature and CO2 concentration with subjective perceptions and sleep quality during transition seasons.. Indoor air. https://doi.org/10.1111/ina.12809.睡眠前の環境を少し暖かくし、換気を良くしておくこと（室内の CO2 濃度を低く保つこと）は、季節の変わり目の睡眠の質に良い影響を与える可能性があります。
Caplan, A., McGee, G., & Magnus, D. (1999). What is immoral about eugenics?. BMJ, 319 7220, 1284-5 . 優生学は、人種衛生と人類の改善の名の下に、恐怖、悲惨、騒乱の歴史があるため、道徳的に間違っていると考えられています。
Buchanan, A. (2007). Institutions, Beliefs and Ethics: Eugenics as a Case Study*. Journal of Political Philosophy, 15, 22-45. https://doi.org/10.1111/J.1467-9760.2007.00250.X. 遺伝子の伝播を防ぐための強制的な不妊手術や殺害を含む強制的な消極的優生学は、権利に基づく道徳を放棄して結果主義を優先したため、大きな誤りであった。
Agar, N. (2018). Why We Should Defend Gene Editing as Eugenics.. Cambridge quarterly of healthcare ethics : CQ : the international journal of healthcare ethics committees, 28 1, 9-19 . https://doi.org/10.1017/S0963180118000336. 遺伝子編集の一部の用途は道徳的に問題のある範疇に入るため、それを優生学として認識することは、人間の遺伝物質を選択または改変することの危険性を明確にするのに役立ちます。
Suckling, R. (2000). Eugenics debate. BMJ : British Medical Journal, 320, 873. https://doi.org/10.1136/BMJ.320.7238.873. 優生学は、繁殖を制御する強制と望ましい特性の主観性により道徳的に間違っていると考えられており、擁護することが困難です。
Gillon, R. (1998). Eugenics, contraception, abortion and ethics.. Journal of Medical Ethics, 24, 219 – 220. https://doi.org/10.1136/jme.24.4.219. 優生学は、人々の選択に対して特別な繊細さと尊重が求められる私生活の領域において、国家が自由とプライバシーを無視するものであり、道徳的に間違っていると考えられています。
Wachbroit, R. (1987). What’s Wrong with Eugenics?. Philosophy and Public Policy Quarterly, 7, 6-9. https://doi.org/10.13021/G8PPPQ.71987.1010. 優生学は、私的な事柄への好ましくない介入と、潜在的に強制を伴うため、道徳的に問題がある。
Steiner, H. (1995). Persons of lesser values–moral argument and the “final solution”.. Journal of applied philosophy, 12 2, 129-41 . https://doi.org/10.1111/J.1468-5930.1995.TB00128.X. 優生学は、人間の健康と生殖に関する広く信じられている価値観に関係しており、個人を道徳的に嘆かわしい危険な道に導くため、道徳的に間違っていると考えられています。
Caplan, A., McGee, G., & Magnus, D. (1999). What is immoral about eugenics?. BMJ, 319, 1284. https://doi.org/10.1136/BMJ.319.7220.1284. 優生学は、その恐ろしい虐待の歴史と、危険な道徳観の再発の危険性から、道徳的に間違っていると考えられています。
Paul, D. (2014). What Was Wrong with Eugenics? Conflicting Narratives and Disputed Interpretations. Science & Education, 23, 259-271. https://doi.org/10.1007/S11191-012-9556-3. 優生学の歴史からは、優生学の根本的な誤りに関する異なる概念や生殖技術に対する異なる熱意に結びついた、さまざまな道徳観念が引き出されてきた。
Gaschler, M., & Stockwell, B. (2017). Lipid peroxidation in cell death.. Biochemical and biophysical research communications, 482 3, 419-425 . https://doi.org/10.1016/j.bbrc.2016.10.086. 脂質過酸化は細胞膜を変化させ、タンパク質と核酸の共有結合修飾を引き起こし、細胞死と疾患において重要な役割を果たします。
Mylonas, C., & Kouretas, D. (1999). Lipid peroxidation and tissue damage.. In vivo, 13 3, 295-309 . 脂質過酸化は、いくつかの疾患状態の発症において重要なステップであり、重大な組織損傷を引き起こす可能性があります。
Miyazawa, T. (2021). Lipid hydroperoxides in nutrition, health, and diseases. Proceedings of the Japan Academy. Series B, Physical and Biological Sciences, 97, 161 – 196. https://doi.org/10.2183/pjab.97.010. 脂質過酸化は加齢に伴う疾患と関連しており、その反応メカニズムを理解することで社会の健康と寿命を向上させることができます。
Terao, J. (1988). Lipid Peroxides in Foods. Journal of Japan Oil Chemists Society, 37, 878-884. https://doi.org/10.5650/JOS1956.37.878. 食品中の脂質過酸化生成物は、毒性や発がん性を引き起こし、人体に有害であると考えられます。
Pritchard, E., & Singh, H. (1960). Lipid peroxidation in tissues of vitamin E deficient rats.. Biochemical and Biophysical Research Communications, 2, 184-188. https://doi.org/10.1016/0006-291X(60)90009-7. 脂質過酸化物は構造的および代謝的な損傷を引き起こす可能性があり、ビタミン E 欠乏ラットの赤血球が溶血しやすくなる原因となります。
Esterbauer, H. (1993). Cytotoxicity and genotoxicity of lipid-oxidation products.. The American journal of clinical nutrition, 57 5 Suppl, 779S-785S; discussion 785S-786S . https://doi.org/10.1093/ajcn/57.5.779S. 食物とともに摂取されたり、体内で生成されたりした脂質酸化生成物は、動物における腫瘍の発生頻度や動脈硬化の発生率を増加させ、健康上のリスクとなります。
Helbock, H., Motchnik, P., & Ames, B. (1993). Toxic hydroperoxides in intravenous lipid emulsions used in preterm infants.. Pediatrics, 91 1, 83-7 . https://doi.org/10.1542/peds.91.1.83. 脂質過酸化はアラキドン酸代謝を変化させ、内因性脂質を損傷し、変異原性物質や発がん物質となる可能性があります。
Forcina, G., & Dixon, S. (2019). GPX4 at the Crossroads of Lipid Homeostasis and Ferroptosis. PROTEOMICS, 19. https://doi.org/10.1002/pmic.201800311. 脂質過酸化は膜損傷や細胞死につながる可能性があり、GPX4 の機能を阻害すると鉄依存性の細胞死であるフェロトーシスを引き起こす可能性があります。
Mataix, J., Quiles, J., Huertas, J., Battino, M., & Mañas, M. (1998). Tissue specific interactions of exercise, dietary fatty acids, and vitamin E in lipid peroxidation.. Free radical biology & medicine, 24 4, 511-21 . https://doi.org/10.1016/S0891-5849(97)00288-8. 脂質過酸化は、運動、食事中の脂肪酸、運動によって引き起こされ、心臓よりも肝臓と筋肉の方が影響を受けやすいです。
Gutteridge, J., & Halliwell, B. (1990). The measurement and mechanism of lipid peroxidation in biological systems.. Trends in biochemical sciences, 15 4, 129-35 . https://doi.org/10.1016/0968-0004(90)90206-Q. 脂質過酸化は多くの病態における組織損傷の結果として発生する可能性があり、時には組織損傷の悪化に大きく寄与することがあります。
Living Mysteries: Meet Earth’s simplest animal Tiny Trichoplax, discovered in a fish tank, provides a window into the origin of animals https://www.snexplores.org/article/living-mysteries-meet-earths-simplest-animal
Evolution of Digestion in Kingdom Animalia http://www.katebrilakis.com/112digestionevolution.html
15.1 Digestive Systems https://opentextbc.ca/biology/chapter/15-1-digestive-systems/
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