Galactoglucomannan-rich hemicellulose extract from Norway spruce (Picea abies) exerts beneficial effects on chronic prostatic inflammation and lower urinary tract symptoms in vivo

Galactoglucomannan (GGM) is the main hemicellulose class in wood of coniferous trees and could be potentially utilized as a possible health-promoting substance for food and pharmaceutical industry. Our aim was to evaluate effects of orally administered GGM-rich extract from Norway spruce in a rat model of chronic prostatitis associated with lower urinary tract symptoms (LUTS). Prostatic inflammation and LUTS was induced in male rats using testosterone and 17 beta-estradiol exposure for 18 weeks. Rats were treated with 2% GGM dissolved in drinking water during weeks 13-18. Pelvic pain response, LUT function and histopathological evaluation of the prostate were assessed. The results show that hormonal exposure induced LUTS seen as decreased urine flow rate, increased bladder pressure, voiding times, bladder capacity and residual urine volumes. GGM had positive effects on urodynamical parameters by decreasing the basal bladder pressure, increasing the urine flow rate and volume, reducing the residual volume and increasing micturition intervals. GGM reduced the extent of the hormone exposure-induced prostatic inflammation. Increase of pelvic pain induced by hormone exposure was only slightly affected by GGM treatment. The results suggest that orally administered GGM may have potential usage for improving lower urinary tract function associated with chronic prostatic inflammation. (C) 2017 Elsevier B.V. All rights reserved

Proprietary Reasons and Joint Action

Some of the reasons one acts on in joint action are shared with fellow participants. But others are proprietary: reasons of one’s own that have no direct practical significance for other participants. The compatibility of joint action with proprietary reasons serves to distinguish the former from other forms of collective agency; moreover, it is arguably a desirable feature of joint action. Advocates of “team reasoning” link the special collective intention individual participants have when acting together with a distinctive form of practical reasoning that purports to put individuals in touch with group or collective reasons. Such views entail the surprising conclusion that one cannot engage in joint action for proprietary reasons. Suppose we understand the contrast between minimal and robust forms of joint action in terms of the extent to which participants act on proprietary reasons as opposed to shared reasons. Then, if the team reasoning view of joint intention and action is correct, it makes no sense to talk of minimal joint action. As soon as the reason for which one participates is proprietary, then one is not, on this view, genuinely engaged in joint action

Constraint rule-based programming of norms for electronic institutions

Peer reviewedPostprin

Biomonitoring of Indoor Air Fungal or Chemical Toxins with Caenorhabditis elegans nematodes

Bad indoor air quality due to toxins and other impurities can have a negative impact on human well-being, working capacity and health. Therefore, reliable methods to monitor the health risks associated with exposure to hazardous indoor air agents are needed. Here, we have used transgenic Caenorhabditis elegans nematode strains carrying stress-responsive fluorescent reporters and evaluated their ability to sense fungal or chemical toxins, especially those that are present in moisture-damaged buildings. Liquid-based or airborne exposure of nematodes to mycotoxins, chemical agents or damaged building materials reproducibly resulted in time- and dose-dependent fluorescent responses, which could be quantitated by either microscopy or spectrometry. Thus, the C. elegans nematodes present an easy, ethically acceptable and comprehensive in vivo model system to monitor the response of multicellular organisms to indoor air toxicity.Peer reviewe

Epistemic Dependence and Collective Scientific Knowledge

I argue that scientific knowledge is collective knowledge, in a sense to be specified and defended. I first consider some existing proposals for construing collective knowledge and argue that they are unsatisfactory, at least for scientific knowledge as we encounter it in actual scientific practice. Then I introduce an alternative conception of collective knowledge, on which knowledge is collective if there is a strong form of mutual epistemic dependence among scientists, which makes it so that satisfaction of the justification condition on knowledge ineliminably requires a collective. Next, I show how features of contemporary science support the conclusion that scientific knowledge is collective knowledge in this sense. Finally, I consider implications of my proposal and defend it against objections. © 2013 Springer Science+Business Media Dordrecht

Alendronate-induced disruption of actin cytoskeleton and inhibition of migration/invasion are associated with cofilin downregulation in PC-3 prostate cancer cells

Bisphosphonates are used for prevention of osteoporosis and metastatic bone diseases. Anti-invasive effects on various cancer cells have also been reported, but the mechanisms involved are not well-understood. We investigated the effects of the nitrogen-containing bisphosphonate alendronate (ALN) on the regulation of actin cytoskeleton in PC-3 cells. We analyzed the ALN effect on the organization and the dynamics of actin, and on the cytoskeleton-related regulatory proteins cofilin, p21-associated kinase 2 (PAK2), paxillin and focal adhesion kinase. Immunostainings of cofilin in ALN-treated PC-3 cells and xenografts were performed, and the role of cofilin in ALN-regulated F-actin organization and migration/invasion in PC-3 cells was analyzed using cofilin knockdown and transfection. We demonstrate that disrupted F-actin organization and decreased cell motility in ALN-treated PC-3 cells were associated with decreased levels of total and phosphorylated cofilin. PAK2 levels were also lowered but adhesion-related proteins were not altered. The knockdown of cofilin similarly impaired F-actin organization and decreased invasion of PC-3 cells, whereas in the cells transfected with a cofilin expressing vector, ALN treatment did not decrease cellular cofilin levels and migration as in mock transfected cells. ALN also reduced immunohistochemical staining of cofilin in PC-3 xenografts. Our results suggest that reduction of cofilin has an important role in ALN-induced disruption of the actin cytoskeleton and inhibition of the PC-3 cell motility and invasion. These data also support the idea that the nitrogen-containing bisphosphonates could be efficacious in inhibition of prostate cancer invasion and metastasis, if delivered in a pharmacological formulation accessible to the tumors.</p

Increased Expression and Altered Cellular Localization of Fibroblast Growth Factor Receptor-Like 1 (FGFRL1) Are Associated with Prostate Cancer Progression

Fibroblast growth factor receptors (FGFRs) 1–4 are involved in prostate cancer (PCa) regulation, but the role of FGFR-like 1 (FGFRL1) in PCa is unclear. FGFRL1 expression was studied by qRT-PCR and immunohistochemistry of patient tissue microarrays (TMAs) and correlated with clinical patient data. The effects of FGFRL1 knockdown (KD) in PC3M were studied in in vitro culture models and in mouse xenograft tumors. Our results showed that FGFRL1 was significantly upregulated in PCa. The level of membranous FGFRL1 was negatively associated with high Gleason scores (GSs) and Ki67, while increased cytoplasmic and nuclear FGFRL1 showed a positive correlation. Cox regression analysis indicated that nuclear FGFRL1 was an independent prognostic marker for biochemical recurrence after radical prostatectomy. Functional studies indicated that FGFRL1-KD in PC3M cells increases FGFR signaling, whereas FGFRL1 overexpression attenuates it, supporting decoy receptor actions of membrane-localized FGFRL1. In accordance with clinical data, FGFRL1-KD markedly suppressed PC3M xenograft growth. Transcriptomics of FGFRL1-KD cells and xenografts revealed major changes in genes regulating differentiation, ECM turnover, and tumor–stromal interactions associated with decreased growth in FGFRL1-KD xenografts. Our results suggest that FGFRL1 upregulation and altered cellular compartmentalization contribute to PCa progression. The nuclear FGFRL1 could serve as a prognostic marker for PCa patients

Increased Expression and Altered Cellular Localization of Fibroblast Growth Factor Receptor-Like 1 (FGFRL1) Are Associated with Prostate Cancer Progression

Fibroblast growth factor receptors (FGFRs) 1–4 are involved in prostate cancer (PCa) regulation, but the role of FGFR-like 1 (FGFRL1) in PCa is unclear. FGFRL1 expression was studied by qRT-PCR and immunohistochemistry of patient tissue microarrays (TMAs) and correlated with clinical patient data. The effects of FGFRL1 knockdown (KD) in PC3M were studied in in vitro culture models and in mouse xenograft tumors. Our results showed that FGFRL1 was significantly upregulated in PCa. The level of membranous FGFRL1 was negatively associated with high Gleason scores (GSs) and Ki67, while increased cytoplasmic and nuclear FGFRL1 showed a positive correlation. Cox regression analysis indicated that nuclear FGFRL1 was an independent prognostic marker for biochemical recurrence after radical prostatectomy. Functional studies indicated that FGFRL1-KD in PC3M cells increases FGFR signaling, whereas FGFRL1 overexpression attenuates it, supporting decoy receptor actions of membrane-localized FGFRL1. In accordance with clinical data, FGFRL1-KD markedly suppressed PC3M xenograft growth. Transcriptomics of FGFRL1-KD cells and xenografts revealed major changes in genes regulating differentiation, ECM turnover, and tumor–stromal interactions associated with decreased growth in FGFRL1-KD xenografts. Our results suggest that FGFRL1 upregulation and altered cellular compartmentalization contribute to PCa progression. The nuclear FGFRL1 could serve as a prognostic marker for PCa patients