This study will examine the introduction, development and popularity of flower still lives as well as of Dutch horticulture, along with Holland’s early flower trade and its effect on Tulipmania, ...which took place during the Baroque era in Europe from 1636 to 1637. The highest-ranked genres, including history paintings, portraits, and altarpieces were slowly replaced by formerly less-regarded genres, such as genre paintings, landscape paintings, and still-lives found a new audience in seventeenth-century Holland. Artists such as Ambrosius Bosschaert and Jan Brueghel the Elder specialized in flower still lifes, depicting elegant vases holding large varieties of perfect flowers. Focusing on Ambrosius Bosschaert’s Flower Still Life, created in 1614 using oil on copper, this paper will examine the relationship between the popularity of horticulture and flower still lives in regard to their effects on the contemporary Dutch economy. First, the painting's formal elements will be analyzed, followed by a brief biography of Ambrosius Bosschaert, specifically discussing the influences on his art and his role as a pioneer in the genre of flower still lives. It will also study the interdisciplinary relationship between Art and Economics and implement past problems to identify similar market issues in the 21st century.
The role of dysregulation of mRNA alternative splicing (AS) in the development and progression of solid tumors remains to be defined. Here we describe the first comprehensive AS landscape in the ...spectrum of human prostate cancer (PCa) evolution. We find that the severity of splicing dysregulation correlates with disease progression and establish intron retention as a hallmark of PCa stemness and aggressiveness. Systematic interrogation of 274 splicing-regulatory genes (SRGs) uncovers prevalent genomic copy number variations (CNVs), leading to mis-expression of ~68% of SRGs during PCa development and progression. Consequently, many SRGs are prognostic. Surprisingly, androgen receptor controls a splicing program distinct from its transcriptional regulation. The spliceosome modulator, E7107, reverses cancer aggressiveness and inhibits castration-resistant PCa (CRPC) in xenograft and autochthonous PCa models. Altogether, our studies establish aberrant AS landscape caused by dysregulated SRGs as a hallmark of PCa aggressiveness and the spliceosome as a therapeutic vulnerability for CRPC.
We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three ...decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease.
Single atom nonmetal 2D nanomaterials have shown considerable potential in cancer nanomedicines, owing to their intriguing properties and biocompatibility. Herein, ultrathin boron nanosheets (B NSs) ...are prepared through a novel top‐down approach by coupling thermal oxidation etching and liquid exfoliation technologies, with controlled nanoscale thickness. Based on the PEGylated B NSs, a new photonic drug delivery platform is developed, which exhibits multiple promising features for cancer therapy and imaging, including: i) efficient NIR‐light‐to‐heat conversion with a high photothermal conversion efficiency of 42.5%, ii) high drug‐loading capacity and triggered drug release by NIR light and moderate acidic pH, iii) strong accumulation at tumor sites, iv) multimodal imaging properties (photoacoustic, photothermal, and fluorescence imaging), and v) complete tumor ablation and excellent biocompatibility. As far as it is known, this is the first report on the top‐down fabrication of ultrathin 2D B NSs by the combined thermal oxidation etching and liquid exfoliation, as well as their application as a multimodal imaging‐guided drug delivery platform. The newly prepared B NSs are also expected to provide a robust and useful 2D nanoplatform for various biomedical applications.
Ultrathin 2D boron (B)‐based nanosheets (NSs) are fabricated through a novel top‐down approach by coupling liquid exfoliating and thermal oxidation etching, and applied to photonic drug delivery for cancer theranostics. The 2D B NS platform exhibits efficient photothermal conversion, high drug loading, spatiotemporally controlled drug release, strong tumor accumulation, good biocompatibility, and significant potential of multimodal imaging‐guided cancer treatment.
Sulforaphane (SFN), a potent nuclear factor erythroid 2-related factor 2 (Nrf2) activator, is present in the species of the Brassicaceae, especially in broccoli sprouts. In this study, the effects of ...SFN against microglial activation and inflammation, and the potential mechanisms involved, were analyzed. As mitogen-activated protein kinase (MAPK) signaling plays a key role in microglial activation and inflammation, we focused on the role of SFN in regulating the MAPK signaling regulation of the inflammatory and anti-inflammatory cascades in lipopolysaccharide (LPS)-activated microglia. The anti-inflammatory and immunomodulatory effects of SFN were explored by evaluating the expression and secretion of inflammatory proteins, cytokines, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and activator protein-1 (AP-1) under pre- and post-treatment conditions. Under the SFN pre- and post-treatment conditions, the MAPK phosphorylation levels were significantly reduced in both acutely and chronically activated microglial cells. SFN also reduced the c-Jun N-terminal kinase (JNK) phosphorylation levels, which subsequently reduced NF-κB and AP-1 signaling. As a result, the expression of the inflammatory mediators (iNOS, COX-2, NO, and PGE2) and proinflammatory cytokines (TNF-α, IL-6, and IL-1β) was decreased. At the same time, SFN increased the expression of Nrf2 and heme oxygenase-1 (HO-1) as well as the production of the anti-inflammatory cytokines IL-10 and IL-4. In conclusion, this study demonstrated that SFN exerts an anti-neuroinflammatory effect on microglia through JNK/AP-1/NF-κB pathway inhibition and Nrf2/HO-1 pathway activation.
Biological electron transport is classically thought to occur over nanometre distances, yet recent studies suggest that electrical currents can run along centimetre-long cable bacteria. The ...phenomenon remains elusive, however, as currents have not been directly measured, nor have the conductive structures been identified. Here we demonstrate that cable bacteria conduct electrons over centimetre distances via highly conductive fibres embedded in the cell envelope. Direct electrode measurements reveal nanoampere currents in intact filaments up to 10.1 mm long (>2000 adjacent cells). A network of parallel periplasmic fibres displays a high conductivity (up to 79 S cm
), explaining currents measured through intact filaments. Conductance rapidly declines upon exposure to air, but remains stable under vacuum, demonstrating that charge transfer is electronic rather than ionic. Our finding of a biological structure that efficiently guides electrical currents over long distances greatly expands the paradigm of biological charge transport and could enable new bio-electronic applications.
Recent studies have analyzed the factors that contribute to variations in the success of crowdfunding campaigns for a specific cancer type; however, little is known about the influential factors ...among crowdfunding campaigns for multiple cancers.
The purpose of this study was to examine the relationship between project features and the success of cancer crowdfunding campaigns and to determine whether text features affect campaign success for various cancers.
Using cancer-related crowdfunding projects on the GoFundMe website, we transformed textual descriptions from the campaigns into structured data using natural language processing techniques. Next, we used penalized logistic regression and correlation analyses to examine the influence of project and text features on fundraising project outcomes. Finally, we examined the influence of campaign description sentiment on crowdfunding success using Linguistic Inquiry and Word Count software.
Campaigns were significantly more likely to be successful if they featured a lower target amount (Goal amount, β=-1.949, z score=-82.767, P<.001) for fundraising, a higher number of previous donations, agency (vs individual) organizers, project pages containing updates, and project pages containing comments from readers. The results revealed an inverted U-shaped relationship between the length of the text and the amount of funds raised. In addition, more spelling mistakes negatively affected the funds raised (Number of spelling errors, β=-1.068, z score=-38.79, P<.001).
Difficult-to-treat cancers and high-mortality cancers tend to trigger empathy from potential donors, which increases the funds raised. Gender differences were observed in the effects of emotional words in the text on the amount of funds raised. For cancers that typically occur in women, links between emotional words used and the amount of funds raised were weaker than for cancers typically occurring among men.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We reported that amyloid β peptide (Aβ42) activated neutral SMase 2 (nSMase2), thereby increasing the concentration of the sphingolipid ceramide in astrocytes. Here, we show that Aβ42 induced ...mitochondrial fragmentation in wild-type astrocytes, but not in nSMase2-deficient cells or astrocytes treated with fumonisin B1 (FB1), an inhibitor of ceramide synthases. Unexpectedly, ceramide depletion was concurrent with rapid movements of mitochondria, indicating an unknown function of ceramide for mitochondria. Using immunocytochemistry and super-resolution microscopy, we detected ceramide-enriched and mitochondria-associated membranes (CEMAMs) that were codistributed with microtubules. Interaction of ceramide with tubulin was confirmed by cross-linking to N-9-(3-pent-4-ynyl-3-H-diazirine-3-yl)-nonanoyl-D-erythro-sphingosine (pacFACer), a bifunctional ceramide analog, and binding of tubulin to ceramide-linked agarose beads. Ceramide-associated tubulin (CAT) translocated from the perinuclear region to peripheral CEMAMs and mitochondria, which was prevented in nSMase2-deficient or FB1-treated astrocytes. Proximity ligation and coimmunoprecipitation assays showed that ceramide depletion reduced association of tubulin with voltage-dependent anion channel 1 (VDAC1), an interaction known to block mitochondrial ADP/ATP transport. Ceramide-depleted astrocytes contained higher levels of ATP, suggesting that ceramide-induced CAT formation leads to VDAC1 closure, thereby reducing mitochondrial ATP release, and potentially motility and resistance to Aβ42. Our data also indicate that inhibiting ceramide generation may protect mitochondria in Alzheimer's disease.
Accumulating evidence indicates that neuroinflammation contributes to the pathogenesis and exacerbation of neurodegenerative disorders, such as Alzheimer's disease (AD). Sphingosine‐1‐phosphate (S1P) ...is a pleiotropic bioactive lipid that regulates many pathophysiological processes including inflammation. We present evidence here that the spinster homolog 2 (Spns2), a S1P transporter, promotes microglia pro‐inflammatory activation in vitro and in vivo. Spns2 knockout (Spns2KO) in primary cultured microglia resulted in significantly reduced levels of pro‐inflammatory cytokines induced by lipopolysaccharide (LPS) and amyloid‐beta peptide 1–42 oligomers (Aβ42) when compared with littermate controls. Fingolimod (FTY720), a S1P receptor 1 (S1PR1) functional antagonist and FDA approved drug for relapsing–remitting multiple sclerosis, partially blunted Aβ42‐induced pro‐inflammatory cytokine generation, suggesting that Spns2 promotes microglia pro‐inflammatory activation through S1P‐signaling. Spns2KO significantly reduced Aβ42‐induced nuclear factor kappa B (NFκB) activity. S1P increased, while FTY720 dampened, Aβ42‐induced NFκB activity, suggesting that Spns2 activates microglia inflammation through, at least partially, NFκB pathway. Spns2KO mouse brains showed significantly reduced Aβ42‐induced microglia activation/accumulation and reduced levels of pro‐inflammatory cytokines when compared with age‐matched controls. More interestingly, Spns2KO ameliorated Aβ42‐induced working memory deficit detected by Y‐Maze. In summary, these results suggest that Spns2 promotes pro‐inflammatory polarization of microglia and may play a crucial role in AD pathogenesis.
Main Points
Using a mouse line deficient for the S1P transporter, Spns2, we demonstrate that Spns2 promotes Aβ42‐induced pro‐inflammatory activation of microglia through NFκB pathway and contributes to Aβ42‐induced cognitive decline.
These data suggest that Spns2 is a potential new mediator of Aβ42‐induced pro‐inflammatory polarization of microglia and may play a role in AD pathogenesis.
After an infection, pathogen-specific tissue-resident memory T cells (TRM cells) persist in nonlymphoid tissues to provide rapid control upon reinfection, and vaccination strategies that create TRM ...cell pools at sites of pathogen entry are therefore attractive. However, it is not well understood how TRM cells provide such pathogen protection. Here, we demonstrate that activated TRM cells in mouse skin profoundly alter the local tissue environment by inducing a number of broadly active antiviral and antibacterial genes. This “pathogen alert” allows skin TRM cells to protect against an antigenically unrelated virus. These data describe a mechanism by which tissue-resident memory CD8⁺ T cells protect previously infected sites that is rapid, amplifies the activation of a small number of cells into an organ-wide response, and has the capacity to control escape variants.
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