Our understanding of breast cancer biology, and our ability to manipulate breast cancers have grown exponentially in the last 20 years. Much of that expansion has focused on the roles of steroids in ...driving these neoplasms. Initially this research focused on estrogens and progesterone receptors, and more recently on androgen actions in breast cancers. This review aims to make the case for glucocorticoids as the next essential steroid subclass that contributes significantly to our understanding of steroidogenic regulation of these neoplasms. Glucocorticoids have the potential to play multiple roles in the regulation of breast cancers including their control of cellular differentiation, apoptosis and proliferation. Beyond this they also act as a master integrator of organ homeostats in relation to such as circadian rhythms and stress responses. Therefore a better understanding of glucocorticoids and breast cancer could help to explain some of the epidemiological links between circadian disruption and/or stress and breast cancer development. Finally glucocorticoids are currently used during chemotherapeutic treatment in breast cancer therapy and yet results of various studies suggest that this may have an adverse impact on treatment success. This review aims to summarise the current evidence for glucocorticoids as actors in breast cancer and then suggest future essential approaches in order to determine the roles of glucocorticoids in this disease.
•Glucocorticoids may impact molecular and cellular pathways in breast cancers.•Glucocorticoid receptor is expressed in a large number of breast cancers, including in the difficult to treat TNBC subtype.•This review highlights the scope of GR signalling in breast cancers.
Liver resection is commonly performed under ischemic conditions, resulting in two types of insult to the remnant liver: ischemia reperfusion injury (IRI) and loss of liver mass. Complement inhibition ...is recognized as a potential therapeutic modality for IRI, but early complement activation products are also essential for liver regeneration. We describe a novel site-targeted murine complement inhibitor, CR2-CD59, which specifically inhibits the terminal membrane attack complex (MAC), and we use this protein to investigate the complement-dependent balance between liver injury and regeneration in a clinical setting of pharmacological inhibition. CR2-CD59 did not impact in vivo generation of C3 and C5 activation products but was as effective as the C3 activation inhibitor CR2-Crry at ameliorating hepatic IRI, indicating that the MAC is the principle mediator of hepatic IRI. Furthermore, unlike C3 or C5 inhibition, CR2-CD59 was not only protective but significantly enhanced hepatocyte proliferation after partial hepatectomy, including when combined with ischemia and reperfusion. Remarkably, CR2-CD59 also enhanced regeneration after 90% hepatectomy and improved long-term survival from 0 to 70%. CR2-CD59 functioned by increasing hepatic TNF and IL-6 levels with associated STAT3 and Akt activation, and by preventing mitochondrial depolarization and allowing recovery of ATP stores.
Of 731 restricted antimicrobial prescriptions subject to antimicrobial stewardship program (ASP) prospective audit and feedback (PAF) over a 3-year period, 598 PAF recommendations (82%) were fully ...accepted. Physician auditors had an increased odds of PAF recommendation acceptance, reinforcing the complementary role of the ASP physician in the multidisciplinary ASP team.
Contested Devotion Sutton, M. Keely
Asian ethnology,
03/2022, Letnik:
81, Številka:
1/2
Journal Article
Recenzirano
Odprti dostop
This article examines three Sufi devotional songs (māla pāṭṭŭs), from the seventeenth to nineteenth centuries, from the Mappila Muslim poetic corpus (māppiḷa pāṭṭŭ) of Kerala, India. Close ...examination of the Mappila song literature provides information and historical detail about a community for which there are limited noncolonial sources. More specifically, an examination of the content, poetic features, and changing mediums and performative contexts of these particular māla pāṭṭŭs foregrounds the Mappila community’s multivocal and complex religious development and history. The article also highlights the ways in which the process of folklorization is both transforming Mappila songs into commodities and simultaneously keeping the māla songs available via the internet, thus preserving these practices as cultural heritage and a living practice.
While the clinical benefit of androgen-based therapeutics in breast cancer has been known since the 1940s, we have only recently begun to fully understand the mechanisms of androgen action in breast ...cancer. Androgen signalling pathways can have either beneficial or deleterious effects in breast cancer depending on the breast cancer subtype and intracellular context. This review discusses our current knowledge of androgen signalling in breast cancer, including the relationship between serum androgens and breast cancer risk, the prognostic significance of androgen receptor (AR) expression in different breast cancer subtypes and the downstream molecular pathways mediating androgen action in breast cancer cells. Intracrine androgen metabolism has also been discussed and proposed as a potential mechanism that may explain some of the reported differences regarding dichotomous androgen actions in breast cancers. A better understanding of AR signalling in this disease is critical given the current resurgence in interest in utilising contemporary AR-directed therapies for breast cancer and the need for biomarkers that will accurately predict clinical response.
The amphibian complement system and chytridiomycosis Rodriguez, Keely M.; Voyles, Jamie
Journal of experimental zoology. Part A, Ecological and integrative physiology,
December 1, 2020, Letnik:
333, Številka:
10
Journal Article
Odprti dostop
Understanding host immune function and ecoimmunology is increasingly important at a time when emerging infectious diseases (EIDs) threaten wildlife. One EID that has emerged and spread widely in ...recent years is chytridiomycosis, caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), which is implicated unprecedented amphibian declines around the world. The impacts of Bd have been severe for many amphibian species, but some populations have exhibited signs of persistence, and even recovery, in some regions. Many mechanisms may underpin this pattern and amphibian immune responses are likely one key component. Although we have made great strides in understanding amphibian immunity, the complement system remains poorly understood. The complement system is a nonspecific, innate immune defense that is known to enhance other immune responses. Complement activation can occur by three different biochemical pathways and result in protective mechanisms, such as inflammation, opsonization, and pathogen lysis, thereby providing protection to the host. We currently lack an understanding of complement pathway activation for chytridiomycosis, but several studies have suggested that it may be a key part of an early and robust immune response that confers host resistance. Here, we review the available research on the complement system in general as well as amphibian complement responses to Bd infection. Additionally, we propose future research directions that will increase our understanding of the amphibian complement system and other immune responses to Bd. Finally, we suggest how a deeper understanding of amphibian immunity could enhance the conservation and management of amphibian species that are threatened by chytridiomycosis.
The fungal pathogen Batrachochytrium dendrobatidis (Bd), is implicated in worldwide amphibian declines. The complement system is a nonspecific, innate immune defense that is known to enhance other immune responses. Here, we address what is known about the complement system in amphibians and how it may respond to infection with Bd.
Highlights
The complement system is an immune component present in vertebrates, but little is known about its role in amphibian chytridiomycosis.
We review recent research, current gaps in knowledge, and we suggest future research to fill these gaps.
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•A simple, hormone-free micropropagation procedure for Cannabis sativa.•Isolation of cannabis leaf protoplasts with 2 million/g yield and 82 % viability.•Transient transformation of ...protoplasts with up to 31 % efficiency.•Auxin-responsive reporter-gene activation measured using flow cytometry.
Cannabis sativa L. is a valuable, up-and-coming industrial crop with a substantially growing market. However, due to an extended period of legal restriction, research with cannabis has been limited, particularly in laboratory settings. Expanding the application of biotechnological techniques to cannabis can facilitate addressing species-specific impediments to improving crop traits and further fundamental understanding of its intricacies. Here, we describe application of protoplast transformation for the study of transient gene expression in a low-THC cannabis cultivar. To produce explant tissue as a source of protoplasts, a method for hormone-free in vitro micropropagation is established. Protoplasts are isolated from young leaves of the micropropagated stocks and transiently transformed with plasmid DNA carrying a fluorescent marker gene. This is the first report of protoplast transformation in this species. A protoplast isolation yield is achieved of up to 2 × 106 cells per gram of leaf material, vitality staining shows that up to 82 % of isolated protoplasts are viable, and quantification of the cells expressing a fluorescent protein indicates that up to 31 % of the cells can be successfully transformed. Additionally, protoplasts are transformed with an auxin-responsive reporter gene and the reaction to treatment with indole-3-acetic acid is quantified using flow cytometry. This work demonstrates that relatively minor modification of standard techniques can be used to study this important emerging crop.
Hormonal cancers affect over 400,000 men and women and contribute collectively to over 100,000 deaths in the United States alone. Thanks to advances in the understanding of these cancers at the ...molecular level and to the discovery of several disease-modifying therapeutics, the last decade has seen a plateauing or even a decreasing trend in the number of deaths from these cancers. These advanced therapeutics not only effectively slow the growth of hormonal cancers, but also provide an insight on how these cancers become refractory and evolve as an altogether distinct subset. This review summarizes the current therapeutic trends in hormonal cancers, with focus on prostate, breast and ovarian cancers. The review discusses the clinical drugs being used now, promising molecules that are going through various stages of development and makes some predictions on how the therapeutic landscape will shift in the next decade.
The primate retina contains a specialized, cone-rich macula, which mediates high acuity and color vision. The spatial resolution provided by the neural retina at the macula is optimized by ...stereotyped retinal blood vessel and ganglion cell axon patterning, which radiate away from the macula and reduce shadowing of macular photoreceptors. However, the genes that mediate these specializations, and the reasons for the vulnerability of the macula to degenerative disease, remain obscure. The aim of this study was to identify novel genes that may influence retinal vascular patterning and definition of the foveal avascular area.
We used RNA from human fetal retinas at 19-20 weeks of gestation (WG; n=4) to measure differential gene expression in the macula, a region nasal to disc (nasal) and in the surrounding retina (surround) by hybridization to 12 GeneChip microarrays (HG-U133 Plus 2.0). The raw data was subjected to quality control assessment and preprocessing, using GC-RMA. We then used ANOVA analysis (Partek) Genomic Suite 6.3) and clustering (DAVID website) to identify the most highly represented genes clustered according to "biological process." The neural retina is fully differentiated at the macula at 19-20 WG, while neuronal progenitor cells are present throughout the rest of the retina. We therefore excluded genes associated with the cell cycle, and markers of differentiated neurons, from further analyses. Significantly regulated genes (p<0.01) were then identified in a second round of clustering according to molecular/reaction (KEGG) pathway. Genes of interest were verified by quantitative PCR (QRT-PCR), and 2 genes were localized by in situ hybridization.
We generated two lists of differentially regulated genes: "macula versus surround" and "macula versus nasal." KEGG pathway clustering of the filtered gene lists identified 25 axon guidance-related genes that are differentially regulated in the macula. Furthermore, we found significant upregulation of three anti-angiogenic factors in the macula: pigment epithelium derived factor (PEDF), natriuretic peptide precurusor B (NPPB), and collagen type IValpha2. Differential expression of several members of the ephrin and semaphorin axon guidance gene families, PEDF, and NPPB was verified by QRT-PCR. Localization of PEDF and Eph-A6 mRNAs in sections of macaque retina shows expression of both genes concentrates in the ganglion cell layer (GCL) at the developing fovea, consistent with an involvement in definition of the foveal avascular area.
Because the axons of macular ganglion cells exit the retina from around 8 WG, we suggest that the axon guidance genes highly expressed at the macula at 19-20 WG are also involved in vascular patterning, along with PEDF and NPPB. Localization of both PEDF and Eph-A6 mRNAs to the GCL of the developing fovea supports this idea. It is possible that specialization of the macular vessels, including definition of the foveal avascular area, is mediated by processes that piggyback on axon guidance mechanisms in effect earlier in development. These findings may be useful to understand the vulnerability of the macula to degeneration and to develop new therapeutic strategies to inhibit neovascularization.
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