86 research outputs found
Inhibition of Dihydrotestosterone Synthesis in Prostate Cancer by Combined Frontdoor and Backdoor Pathway Blockade
Androgen deprivation therapy (ADT) is palliative and prostate cancer (CaP) recurs as lethal castration-recurrent/resistant CaP (CRPC). One mechanism that provides CaP resistance to ADT is primary backdoor androgen metabolism, which uses up to four 3α-oxidoreductases to convert 5α-androstane-3α,17β-diol (DIOL) to dihydrotestosterone (DHT). The goal was to determine whether inhibition of 3α-oxidoreductase activity decreased conversion of DIOL to DHT. Protein sequence analysis showed that the four 3α-oxidoreductases have identical catalytic amino acid residues. Mass spectrometry data showed combined treatment using catalytically inactive 3α-oxidoreductase mutants and the 5α-reductase inhibitor, dutasteride, decreased DHT levels in CaP cells better than dutasteride alone. Combined blockade of frontdoor and backdoor pathways of DHT synthesis provides a therapeutic strategy to inhibit CRPC development and growth
Understanding and Integrating Local Perceptions of Trees and Forests into Incentives for Sustainable Landscape Management
We examine five forested landscapes in Africa (Cameroon, Madagascar, and Tanzania) and Asia (Indonesia and Laos) at different stages of landscape change. In all five areas, forest cover (outside of protected areas) continues to decrease despite local people’s recognition of the importance of forest products and services. After forest conversion, agroforestry systems and fallows provide multiple functions and valued products, and retain significant biodiversity. But there are indications that such land use is transitory, with gradual simplification and loss of complex agroforests and fallows as land use becomes increasingly individualistic and profit driven. In Indonesia and Tanzania, farmers favor monocultures (rubber and oil palm, and sugarcane, respectively) for their high financial returns, with these systems replacing existing complex agroforests. In the study sites in Madagascar and Laos, investments in agroforests and new crops remain rare, despite government attempts to eradicate swidden systems and their multifunctional fallows. We discuss approaches to assessing local values related to landscape cover and associated goods and services. We highlight discrepancies between individual and collective responses in characterizing land use tendencies, and discuss the effects of accessibility on land management. We conclude that a combination of social, economic, and spatially explicit assessment methods is necessary to inform land use planning. Furthermore, any efforts to modify current trends will require clear incentives, such as through carbon finance. We speculate on the nature of such incentive schemes and the possibility of rewarding the provision of ecosystem services at a landscape scale and in a socially equitable manner
La mirada que pasa: museos, educación pública y visualización de la evidencia científica
Finding alternatives to swidden agriculture: does agroforestry improve livelihood options and reduce pressure on existing forest?
Proteomic Analysis of Charcoal-Stripped Fetal Bovine Serum Reveals Changes in the Insulin-like Growth Factor Signaling Pathway
Charcoal-stripped
fetal bovine serum (CS-FBS) is commonly used
to study androgen responsiveness and androgen metabolism in cultured
prostate cancer (CaP) cells. Switching CaP cells from FBS to CS-FBS
may reduce the activity of androgen receptor (AR), inhibit cell proliferation,
or modulate intracellular androgen metabolism. The removal of proteins
by charcoal stripping may cause changes in biological functions and
has not yet been investigated. Here we profiled proteins in FBS and
CS-FBS using an ion-current-based quantitative platform consisting
of reproducible surfactant-aided precipitation/on-pellet digestion,
long-column nanoliquid chromatography separation, and ion-current-based
analysis. A total of 143 proteins were identified in FBS, among which
14 proteins including insulin-like growth factor 2 (IGF-2) and IGF
binding protein (IGFBP)-2 and -6 were reduced in CS-FBS. IGF-1 receptor
(IGF1R) and insulin receptor were sensitized to IGFs in CS-FBS. IGF-1
and IGF-2 stimulation fully compensated for the loss of AR activity
to maintain cell growth in CS-FBS. Endogenous production of IGF and
IGFBPs was verified in CaP cells and clinical CaP specimens. This
study provided the most comprehensive protein profiles of FBS and
CS-FBS and offered an opportunity to identify new protein regulators
and signaling pathways that regulate AR activity, androgen metabolism,
and proliferation of CaP cells
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