Abstract
The solar active region 12673 produced two successive X-class flares (X2.2 and X9.3) approximately 3 hr apart in 2017 September. The X9.3 flare was the largest recorded solar flare in Solar ...Cycle 24. In this study we perform a data-constrained magnetohydrodynamic simulation taking into account the observed photospheric magnetic field to reveal the initiation and dynamics of the X2.2 and X9.3 flares. According to our simulation, the X2.2 flare is first triggered by magnetic reconnection at a local site where at the photosphere the negative polarity intrudes into the opposite-polarity region. This magnetic reconnection expels the innermost field lines upward, beneath which the magnetic flux rope is formed through continuous reconnection with external twisted field lines. Continuous magnetic reconnection after the X2.2 flare enhances the magnetic flux rope, which is lifted up and eventually erupts via the torus instability. This gives rise to the X9.3 flare.
Vitamin K is a fat-soluble vitamin that was originally found as an essential factor for blood coagulation. With the discovery of its role as a co-factor for γ-glutamyl carboxylase (GGCX), its ...function for blood coagulation was understood as the activation of several blood coagulation factors by their γ-carboxylation. Over the last two decades, other modes of vitamin K actions have been discovered, such as the regulation of transcription by activating the steroid and xenobiotic receptor (SXR), physical association to 17β-Hydroxysteroid dehydrogenase type 4 (17β-HSD4), covalent modification of Bcl-2 antagonist killer 1 (Bak), and the modulation of protein kinase A (PKA) activity. In addition, several epidemiological studies have revealed that vitamin K status is associated with some aging-related diseases including osteoporosis, osteoarthritis, and sarcopenia. Clinical studies on single nucleotide polymorphisms of GGCX suggested an association between higher GGCX activity and bone protective effect, while recent findings using conditional knockout mice implied that a contribution in protective effect for bone loss by GGCX in osteoblastic lineage was unclear. GGCX in other cell lineages or in other tissues might play a protective role for osteoporosis. Meanwhile, animal experiments by our groups among others revealed that SXR, a putative receptor for vitamin K, could be important in the bone metabolism. In terms of the cartilage protective effect of vitamin K, both GGCX- and SXR-dependent mechanisms have been suggested. In clinical studies on osteoarthritis, the γ-carboxylation of matrix Gla protein (MGP) and gla-rich protein (GRP) may have a protective role for the disease. It is also suggested that SXR signaling has protective role for cartilage by inducing family with sequence similarity 20a (
) expression in chondrocytes. In the case of sarcopenia, a high vitamin K status in plasma was associated with muscle strength, large muscle mass, and high physical performance in some observational studies. However, the basic studies explaining the effects of vitamin K on muscular tissue are limited. Further research on vitamin K will clarify new biological mechanisms which contribute to human longevity and health through the prevention and treatment of aging-related musculoskeletal disorders.
The majority of breast cancers are primarily hormone‐sensitive and can be managed by endocrine therapy, although therapy‐resistant or hormone‐refractory cancers need alternative treatments. Recently, ...increasing attention is being paid to RNA‐binding proteins (RBP) in cancer pathophysiology. The precise role of RBP in breast cancer, however, remains to be clarified. We herein show that an RBP non‐POU domain‐containing octamer binding (NONO) plays a critical role in the pathophysiology of breast cancers regardless of their hormone dependency. Clinicopathological and immunohistochemical study of 127 breast cancer cases showed that NONO is a significant independent prognostic factor for breast cancer patients. Notably, siRNA‐mediated NONO knockdown substantially repressed the proliferation of both hormone‐sensitive MCF‐7 and hormone‐refractory MB‐MDA‐231 breast cancer cells. Integrative analysis combined with expression microarray and RIP‐sequencing (RNA immunoprecipitation‐sequencing) showed that NONO post‐transcriptionally regulates the expression of cell proliferation‐related genes by binding to their mRNAs, as exemplified by S‐phase‐associated kinase 2 and E2F transcription factor 8. Overall, these results suggest that NONO is a key regulator for breast cancer proliferation through the pre‐mRNA splicing of cell proliferation‐related genes and could be a potential new diagnostic and therapeutic target for advanced disease.
The present study shows that Drosophila behavior human splicing family RNA‐binding protein NONO plays a critical role in breast cancer tumorigenesis. Clinicopathological study defines that NONO immunoreactivity significantly correlates with poor overall and distant disease‐free survival of breast cancer patients. Cell‐based experiments show that NONO contributes to breast cancer proliferation by regulating SKP2 and E2F8 expression at the post‐transcriptional level. Our findings provide a new cancer strategy by applying NONO as a potential diagnostic and therapeutic target for breast cancer.
Estrogen is an essential sex steroid hormone that functions primarily in female reproductive system, as well as in a variety of tissues and organs with pleiotropic effects, such as in cardiovascular, ...nervous, immune, and musculoskeletal systems. Women with low estrogen, as exemplified by those in postmenopause, are therefore prone to suffer from various disorders, i.e., cardiovascular disease, dementia, metabolic syndrome, osteoporosis, sarcopenia, frailty, and so on. Estrogen regulates the expression of its target genes by binding to its cognate receptors, estrogen receptors (ERs) α and β. Notably, the estrogen-related receptors (ERRs) α, β, and γ are originally identified as orphan receptors that share substantial structural homology and common transcriptional targets with ERs. Accumulating evidence suggests that ERs and ERRs play crucial roles in skeletal muscles, such as muscle mass maintenance, muscle exercise physiology, and muscle regeneration. In this article, we review potential regulatory roles of ERs and ERRs in muscle physiology, particularly with regard to mitochondrial function and metabolism.
•AMD is a late-onset eye disease that impairs central vision among elderly populations.•Lipofuscin accumulation and drusen formation play a role in the pathogenesis of AMD.•Inflammatory and ...angiogenic pathways are implicated in the pathophysiology of AMD.•ARMS2/HTRA1 and CFH are major AMD susceptibility genes identified by GWAS.•Non-genetic factors such as smoking and high fat diet are implicated as risk factors.
Age-related macular degeneration (AMD) is a major late-onset posterior eye disease that causes central vision to deteriorate among elderly populations. The predominant lesion of AMD is the macula, at the interface between the outer retina and the inner choroid. Recent advances in genetics have revealed that inflammatory and angiogenic pathways play critical roles in the pathophysiology of AMD. Genome-wide association studies have identified ARMS2/HTRA1 and CFH as major AMD susceptibility genes. Genetic studies for AMD will contribute to the prevention of central vision loss, the development of new treatment, and the maintenance of quality of vision for productive aging.
Osteoclasts form a specialized cell-matrix adhesion structure, known as the "sealing zone", during bone resorption. The sealing zone is a dynamic actin-rich structure that defines the resorption area ...of the bone. The detailed dynamics and fine structure of the sealing zone have been elusive. Osteoclasts plated on glass do not form a sealing zone, but generate a separate supra-molecular structure called the "podosome belt". Podosomes are integrin-based adhesion complexes involved in matrix adhesion, cell migration, matrix degradation, and mechanosensing. Invadopodia, podosome-like protrusions in cancer cells, are involved in cell invasion into other tissues by promoting matrix degradation. Both podosomes and invadopodia exhibit actin pattern transitions during maturation. We previously found that Arp2/3-dependent actin flow occurs in all observed assembly patterns of podosomes in osteoclasts on glass. It is known that the actin wave in
cells exhibits a similar pattern transition in its evolution. Because of significant advances in our understanding regarding the mechanism of podosomes/invadopodia formation over the last decade, we revisited the structure and function of the sealing zone in this review, highlighting the possible involvement of self-organized actin waves in the organogenesis of the sealing zone.
Estrogens are important endocrine hormones that control physiological functions in reproductive organs, and play a pivotal role in the generation and progression of breast cancer. Therapeutic drugs ...including anti-estrogen and aromatase inhibitors are used to treat patients with breast cancer. The estrogen receptors, ERa and ERβ, function as hormone-dependent transcription factors that directly regulate the expression of their target genes. Therefore, a better understanding of the function and regulation of estrogen-responsive genes provides insight into the gene regulation network associated with breast cancer. Recent technological developments in high- throughput sequencing have enabled the genome-wide identification of estrogen-responsive genes. Further elucidating the estrogen gene cascade is critical for advancements in the diagnosis and treatment of breast cancer.
Solar eruptions are well-known drivers of extreme space weather, which can greatly disturb the Earth's magnetosphere and ionosphere. The triggering process and initial dynamics of these eruptions are ...still an area of intense study. Here we perform a magnetohydrodynamic simulation taking into account the observed photospheric magnetic field to reveal the dynamics of a solar eruption in a real magnetic environment. In our simulation, we confirmed that tether-cutting reconnection occurring locally above the polarity inversion line creates a twisted flux tube, which is lifted into a toroidal unstable area where it loses equilibrium, destroying the force-free state, and driving the eruption. Consequently, a more highly twisted flux tube is built up during this initial phase, which can be further accelerated even when it returns to a stable area. We suggest that a nonlinear positive feedback process between the flux tube evolution and reconnection is the key to ensure this extra acceleration.
Seaports are located in vulnerable areas to climate change impacts: on coasts susceptible to sea-level rise and storms or at mouths of rivers susceptible to flooding. They serve a vital function ...within the local, regional, and global economy. Their locations in the heart of sensitive estuarine environments make it an imperative to minimize the impacts of natural hazards. Climate impacts, like a projected SLR of .6 m to 2 m and doubling of Category 4 and 5 hurricanes by 2100, will result in more extreme events at many seaports. To assess the current state of knowledge on this issue, we surveyed port authorities from around the world about how administrators felt climate change might impact their operations, what sea-level change would create operational problems, and how they planned to adapt to new environmental conditions. The planned rapid expansion of ports reported by the survey respondents indicates that adaptation measures should be considered as ports construct new infrastructure that may still be in use at the end of the century. Respondents agreed that the ports community needs to address this issue and most felt relatively uninformed about potential climate impacts. Although most ports felt that SLR would not be an issue at their port this century, sea-level rise was nevertheless an issue of great concern. Our results suggest opportunities for the scientific community to engage with port practitioners to prepare proactively for climate change impacts on this sector.
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