Non-technical summary
By distinguishing between developed and less developed nations, the concept of development subtly establishes hierarchies and a supposed comparability, which is highly ...ambivalent from a socio-ethical point of view. The idea of holistic development in Catholic social teaching focus on cultural dimensions and therefore sets an important counter accent to the fixation on socio-technically producible and countable things. The Sustainable Development Goals (SDGs) lack a coherence between the social and the ecological components as well as a naming of power conflicts. For a power-critical, postcolonial and participatory concept of development, their interpretation could learn substantially from the encyclical
Laudato si
'.
Technical summary
The paradigm of development is subjected to a radical critique in parts of the academic debate: Is the idea of development, which in a gesture of aid divides the world into “developed” and “underdeveloped” nations and thus establishes a hierarchy, still politically and morally justifiable at all? Has this concept possibly become a backdoor to prolong the old colonial power relations into the 21st century, even to increase them in some cases? Is development one of the great utopias of the 20th century that promised freedom and brought division? Is the ecological overexploitation of global resources the inevitable reverse side of the spread of the Western model of prosperity disguised as “development”? Do the SDGs act subcutaneously as enablers of Western imperial power, or do they represent a genuine paradigm shift? This article explores these questions in four steps: 1. Is the age of development is over? 2. The ideal of “integral development” – steps of a revision process 3. In the tension between ecological and social goals: A Comparison of the “Sustainable Development Goals” and the Encyclical
Laudato si
' 4. Priorities and strategies of a “post-utopian development policy”.
Social media summary
The shadows of colonial thinking are still effective today in development concepts fixated on countable factors of socioeconomic efficiency.
The microbiological diagnosis of periprosthetic joint infection (PJI) is crucial for successful antimicrobial treatment. Cultures have limited sensitivity, especially in patients receiving ...antibiotics. We evaluated the value of multiplex PCR for detection of microbial DNA in sonication fluid from removed orthopedic prostheses. Cases of PJI in which the prosthesis (or part of it) was removed were prospectively included. The removed implant was sonicated, and the resulting sonication fluid was cultured and subjected to multiplex PCR. Of 37 PJI cases (17 hip prostheses, 14 knee prostheses, 4 shoulder prostheses, 1 elbow prosthesis, and 1 ankle prosthesis), pathogens were identified in periprosthetic tissue in 24 (65%) cases, in sonication fluid in 23 (62%) cases, and by multiplex PCR in 29 (78%) cases. The pathogen was detected in 5 cases in sonication fluid only (Propionibacterium acnes in all cases; none of these patients had previously received antibiotics) and in 11 cases by multiplex PCR only (all of these patients had previously received antibiotics). After exclusion of 8 cases caused by P. acnes or Corynebacterium species, which cannot be detected due to the absence of specific primers in the PCR kit, sonication cultures were positive in 17 cases and multiplex PCR sonication cultures were positive in 29 cases (59% versus 100%, respectively; P < 0.01). Among 19 cases (51%) receiving antibiotics, multiplex PCR was positive in all 19 (100%), whereas sonication cultures grew the organism in 8 (42%) (P < 0.01). Multiplex PCR of sonication fluid is a promising test for diagnosis of PJI, particularly in patients who previously received antibiotics. With modified primer sets, multiplex PCR has the potential for further improvement of the diagnosis of PJI.
Non-technical summary
In this paper we discuss current challenges to the sustainability concept. This article focuses on seven dimensions of the concept. These dimensions are crucial for ...understanding sustainability. Even today, the literature contains basic misunderstandings about these seven dimensions. This article sketches such fallacies in the context of global and planetary sustainability. The sustainability concept has been criticized as a content-empty ‘fuzzy notion’ or non-committal ‘all-purpose glue’. This article thus has a critical intention of reflecting the sustainability concept accurately. The aim is to contribute a better understanding of the concept.
Technical summary
This paper focuses on questions related to the normative content of sustainability. Even today, the literature contains basic misunderstandings about this content. So, this article sketches seven such fallacies in the context of global and planetary sustainability. They are partly to blame for the recent discourse about the environment and development ending up in a cul-de-sac, discrediting the term sustainability. This article thus has a critical intention of reflecting the sustainability concept accurately by discussing current challenges. The aim is to contribute a better understanding of the normative aspects of sustainability. By presenting a differentiated analysis of its content the article will provide a reflected version of the sustainability concept, characterized by the following dimensions: (1) ecological: reflection on the conditions and consequences of human activities; (2) political: sustainability as a cross-sectional political guideline; (3) ethical: intergenerational and global responsibility; (4) socio-economic: operationalizing the principle of sustainability; (5) democratic: pluralism, participation and democratic innovation; (6) cultural: lifestyle and a new model of wealth; (7) theological: belief in creation and sustainability. We do not want to offer limited definitions, but rather to stimulate a debate about rehabilitating the sustainability concept. Therefore, these dimensions are crucial for understanding sustainability.
The microRNA encoding genes
miR-34a
and
miR-34b/c
represent direct p53 target genes and possess tumor suppressive properties as they mediate apoptosis, cell cycle arrest, and senescence. We ...previously reported that the
miR-34a
gene is subject to epigenetic inactivation by CpG methylation of its promoter region in primary prostate cancer and melanomas, and in 110 different cancer cell lines of diverse origin. Here we analyzed the methylation status of
miR-34a
and
miR-34b/c
in additional primary tumors of divergent sites. We found methylation of
miR-34a
or
miR-34b/c
in formalin-fixed, paraffin-embedded (FFPE) tumor samples from 178 patients with the following frequencies: colorectal cancer (74%
miR-34a
, 99%
miR-34b/c
;
n
= 114), pancreatic cancer (64%, 100%;
n
= 11), mammary cancer (60%, 90%;
n
= 10), ovarian cancer (62%, 69%;
n
= 13), urothelial cancer (71%, 57%;
n
= 7), and renal cell cancer (58%, 100%;
n
= 12). Furthermore, soft tissue sarcomas showed methylation of
miR-34
gene promoters in FFPE samples (64%, 45%;
n
= 11), in explanted, cultured cells (53%, 40%;
n
= 40), and in frozen tissue samples (75%, 75%,
n
= 8). In the colorectal cancer samples a statistically significant correlation of
miR-34a
methylation and the absence of p53 mutation was detected. With the exception of sarcoma cell lines, the inactivation of
miR-34a
and
miR-34b/c
was concomitant in most cases. These results show that
miR-34
inactivation is a common event in tumor formation, and suggest that CpG methylation of
miR-34a
and
miR-34-b/c
may have diagnostic value. The mutual exclusiveness of
miR-34a
methylation and p53 mutation indicates that
miR-34a
inactivation may substitute for loss of p53 function in cancer.
Purpose: The miR-34 family is directly transactivated by tumor suppressor p53, which is frequently mutated in human epithelial ovarian
cancer (EOC). We hypothesized that miR-34 expression would be ...decreased in EOC and that reconstituted miR-34 expression might
reduce cell proliferation and invasion of EOC cells.
Experimental Designs: miR-34 expression was determined by quantitative reverse transcription-PCR and in situ hybridization in a panel of 83 human EOC samples. Functional characterization of miR-34 was accomplished by reconstitution
of miR-34 expression in EOC cells with synthetic pre-miR molecules followed by determining changes in proliferation, apoptosis,
and invasion.
Results: miR-34a expression is decreased in 100%, and miR-34b*/c in 72%, of EOC with p53 mutation, whereas miR-34a is also downregulated in 93% of tumors with wild-type p53 . Furthermore, expression of miR-34b*/c is significantly reduced in stage IV tumors compared with stage III ( P = 0.0171 and P = 0.0029, respectively). Additionally, we observed promoter methylation and copy number variations at mir-34 . In situ hybridization showed that miR-34a expression is inversely correlated with MET immunohistochemical staining, consistent with
translational inhibition by miR-34a. Finally, miR-34 reconstitution experiments in p53 mutant EOC cells resulted in reduced proliferation, motility, and invasion, the latter of which was dependent on MET expression.
Conclusions: Our work suggests that miR-34 family plays an important role in EOC pathogenesis and reduced expression of miR-34b*/c may
be particularly important for progression to the most advanced stages. Part of miR-34 effects on motility and invasion may
be explained by regulation of MET, which is frequently overexpressed in EOC. Clin Cancer Res; 16(4); 1119–28
Abstract
G
q
proteins are universally important for signal transduction in mammalian cells. The underlying kinetics and transformation from extracellular stimuli into intracellular signaling, however ...could not be investigated in detail so far. Here we present the human Neuropsin (hOPN5) for specific and repetitive manipulation of G
q
signaling in vitro and in vivo with high spatio-temporal resolution. Properties and G protein specificity of hOPN5 are characterized by UV light induced IP
3
generation, Ca
2+
transients and inhibition of G
IRK
channel activity in HEK cells. In adult hearts from a transgenic animal model, light increases the spontaneous beating rate. In addition, we demonstrate light induced contractions in the small intestine, which are not detectable after pharmacological G
q
protein block. All-optical high-throughput screening for TRPC6 inhibitors is more specific and sensitive than conventional pharmacological screening. Thus, we demonstrate specific G
q
signaling of hOPN5 and unveil its potential for optogenetic applications.
Salinomycin is a polyether ionophore antibiotic that has recently been shown to induce cell death in human cancer cells displaying multiple mechanisms of drug resistance. The underlying mechanisms ...leading to cell death after salinomycin treatment have not been well characterized. We therefore investigated the role of salinomycin in caspase dependent and independent cell death in colon cancer (SW480, SW620, RKO) and breast cancer cell lines (MCF-7, T47D, MDA-MB-453).
We detected features of apoptosis in all cell lines tested, but the executor caspases 3 and 7 were only strongly activated in RKO and MDA-MB-453 cells. MCF-7 and SW620 cells instead presented features of autophagy such as cytoplasmic vacuolization and LC3 processing. Caspase proficient cell lines activated autophagy at lower salinomycin concentrations and before the onset of caspase activation. Salinomycin also led to the formation of reactive oxygen species (ROS) eliciting JNK activation and induction of the transcription factor JUN. Salinomycin mediated cell death could be partially inhibited by the free radical scavenger N-acetyl-cysteine, implicating ROS formation in the mechanism of salinomycin toxicity.
Our data indicate that, in addition to its previously reported induction of caspase dependent apoptosis, the initiation of autophagy is an important and early effect of salinomycin in tumor cells.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Decreased expression of the microRNA miR-205 has been observed in multiple tumour types due to its role in the epithelial to mesenchymal transition, which promotes metastasis. We determined the ...expression of miR-205 in 111 archival samples of prostate carcinoma and found it to be strongly reduced in most samples, with a median expression level of 16% in comparison to benign tissue from the same patient. Lower miR-205 expression correlated significantly with tumour size and miR-205 levels decreased with increasing Gleason score from 7a=3+4 to 8=4+4. In addition, we describe the anti-apoptotic protein BCL2 as a target of miR-205, relevant for prostate cancer due to its role in prognosis of primary tumours and in the appearance of androgen independence. The repression of BCL2 by miR-205 was confirmed using reporter assays and western blotting. BCL2 mRNA expression in the same collective of prostate cancer tissue samples was associated with higher Gleason score and extracapsular extension of the tumour (pT3). Consistent with its anti-apoptotic target BCL2, miR-205 promoted apoptosis in prostate cancer cells in response to DNA damage by cisplatin and doxorubicin in the prostate cancer cell lines PC3 and LnCap. MiR-205 also inhibited proliferation in these cell lines.
MicroRNAs (miRNAs: short non-coding RNAs) are emerging as a class of potential novel tumor markers, as their dysregulation is being increasingly reported in various types of cancers. In the present ...study, we investigated the transcription status of miRNA-148a (miR-148a) in human pancreatic ductal adenocarcinoma (PDAC) and its role in the regulation of the dual specificity protein phosphatase CDC25B. We observed that miR-148a exhibited a significant 4-fold down-regulation in PDAC as opposed to normal pancreatic ductal cells. In addition, we observed that stable lentiviral-mediated overexpression of miR-148a in the pancreatic cancer cell line IMIM-PC2, inhibited tumor cell growth and colony formation. Furthermore, CDC25B was identified as a potential target of miR-148a by in silico analysis using PicTar, Targetscan and miRanda in conjunction with gene ontology analysis. The proposed interaction between miR-148a and the 3′ untranslated region (UTR) of CDC25B was verified by in-vitro luciferase assays. We demonstrate that the activity of a luciferase reporter containing the 3′UTR of CDC25B was repressed in the presence of miR-148a mimics, confirming that miR-148a targets the 3′UTR of CDC25B. Finally, CDC25B was down-regulated at the protein level in miR-148a overexpressing IMIM-PC2-cells, and in transiently transfected pancreatic cell lines (as detected by Western blot analysis), as well as in patient tumor samples (as detected by immunohistochemistry). In summary, we identified CDC25B as a novel miR-148a target which may confer a proliferative advantage in PDAC.
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