The objective of the current study was to document naturally occurring levels of BMPs and their inhibitors in human fractures and non-unions. Our hypothesis was that the balance between BMP and BMP-inhibitors differs between healing and non-healing human fractures, which would imply an interventional opportunity. In addition, we also set out to study their co-expression using double and triple immunohistochemistry staining. Fundamental to our hypothesis is a better understanding at the molecular level of why certain fractures Anti-cancer Compound Library solubility dmso heal and others do not. Fracture callus and non-union tissue was obtained during surgery of 16 different patients at the time of operative

repair or revision surgery of the fracture (n = 12) or hypertrophic non-union (n = 4). Three fractures involved the acetabulum (n = 2) or pelvis (n = 1). All other fractures and non-unions pertained to the appendicular skeleton. Although more patients Depsipeptide mouse were treated during this period, representative tissue availability was limited. The definition of a non-union was a fracture that had not healed within 6 months. All patients were treated by the senior author (PK) between 2001 and 2010. Patient characteristics are listed in Table 1. Fracture patients were between 10 and 70 years of age and otherwise in good health. There were 10 males and 2 females. Time to

callus harvest ranged from 2 to 10 weeks. Non-union patients were between 37 and 69 years of age and otherwise in good health. There were 3 males and 1 female. Approval

of the Institutional Review Board (IRB) was obtained where appropriate. Oral consent for removal of the tissue and its storage in the tissue bank for research purposes was obtained from each patient. Individual consent for this specific project was waivered by the ethics committee of the remaining two hospitals since the research was performed on “waste” material, PRKACG stored in a coded fashion. Indications for surgery were nascent (impending) malunion, non-union, and failure of fixation or fractures that were operated on in a delayed fashion. All fractures and non-unions have subsequently successfully healed. After removal from patients, specimens were placed in 10% neutral buffered formalin for 24 h and subsequently decalcified – if needed – in 10% ethylenediamine tetra acetic acid (EDTA), pH 7.2. The tissue was then routinely processed and embedded in paraffin wax. Sequential sections of 5–7 μm thick were prepared for haematoxylin and eosin (H&E) staining and immunohistochemistry (IHC). For immunohistochemistry, samples were fixed in 4% paraformaldehyde overnight, decalcified in 20% ethylene diamine tetra-acetic acid for 3 weeks, embedded in MMA (methylmethacrylate), and sectioned using a Leica RM 2255 microtome (Leica Microsystems, Richmond Hill, ON, Canada). Following deparaffinization and hydration, endogenous peroxidase activity was blocked using 10% hydrogen peroxide for 10 min.

Dogs experiencing grade II or higher nausea or vomiting toxicity score (according to the Veterinary Cooperative Oncology Group—Common Terminology Criteria for Adverse Events [VCOG-CTCAE] v1.0) [20] were treated as clinically indicated with either oral metoclopramide

at a target dose of 0.3 mg/kg per os (PO) three times a day or ondansetron at a target dose of 0.3 to 0.5 mg/kg PO twice a day, depending on clinician preference. The same antiemetic was to be used as required for the duration of the study in each individual dog. Dogs that developed grade II diarrhea were to be treated with oral metronidazole at a target dose of 10 to 15 mg/kg PO twice a day. Dogs were removed from the study if a significant toxicity occurred that precluded continuation of doxorubicin administration at the same dose or if deemed to be clinically necessary for any other reason. Dogs were removed from study at any time if review of the medical record Screening Library purchase indicated a dog did not meet eligibility criteria, if a dog did not receive the drug/agent at the prescribed dose, if progressive disease occurred, if the dog required a significant diet change, or if the owner requested withdrawal from the trial for any reason. As was required at UC Davis for client-owned animals, the study FG-4592 cost design and treatment protocol were evaluated by the Clinical Trials Review Board at the UC Davis VMTH and were granted

approval. One week after each dose of doxorubicin, owners were asked to score their pet’s toxicity on a visual analog scale similar to that reported in Rau et al. [6]. Gastrointestinal toxicity was scored by the owners 1 week after administration of doxorubicin using the visual analog scale as previously published [6]. The mark placed by owners on each scale was given a number between 0 and 4 and corresponded to the VCOG-CTCAE v1.0 toxicity scoring [20]. If owners marked between whole numbers, then a value equal to

the proportion along the scale Selleckchem Staurosporine was given. Neutropenia and thrombocytopenia were assessed from CBC values obtained 7 to 10 days after doxorubicin administration and given a grade using the VCOG-CTCAE v1.0 scheme [20]. Gastrointestinal, constitutional, and hematologic variables were evaluated as both continuous and categorical data. Each mark corresponded to a score from the VCOG-CTCAE v1.0 scheme, yielding a numerical value from 0 (no toxicity) to 4 (life threatening toxicity). Specific categories assessed included appetite, nausea, vomiting, diarrhea, and activity. The owner of one dog performed daily evaluations of toxicity rather than one evaluation at the end of the week. In this case, the highest score for each category was assigned for that dose. In the one dog that was hospitalized due to toxicity, scores were recorded based on the owner’s evaluation but were then updated with information from the medical record during the hospital stay.

The adaptive immune system essentially functions via the production of three key types of effector: antibodies (produced from B cells), cytokines

and cytolytic molecules (produced by T cells) ( Figure 2.6). The first cells to interact with an incoming pathogen are often the phagocytes of the innate immune system, which can engulf and degrade pathogens. However, it is now clearly recognised that professional APCs, typified by DCs, can ingest pathogen-derived proteins, partially digest, process and transport the peptide products to the cell surface, rather than targeting them for complete destruction. These pathogen-derived peptide antigens are bound by a specialised set of receptors known as human leukocyte antigens (HLA) that act as ‘antigen-presenting’ molecules. These molecules are encoded by a gene family called Sorafenib the major histocompatibility complex (MHC). DCs displaying pathogen-derived antigen on the cell surface are Obeticholic Acid in vitro also endowed with migratory properties that allow them to leave the infected site and migrate towards

the nearest lymph node. DCs therefore represent an important cellular messenger, able to transport molecular pathogen fragments to secondary lymphoid organs. Antigen fragments displayed by DCs are destined to activate pathogen-specific T cells residing in the lymph nodes. MHC restriction and T-cell subsets MHC molecules display antigenic peptides to T cells. MHC class I molecules receive endogenous proteins, including those derived from intracellular pathogens,

and are expressed by virtually all nucleated Cediranib (AZD2171) cells of the body. MHC class I peptides are recognised by the T-cell receptor (TCR) expressed by CD8+ T cells. MHC class II molecules are usually expressed by a restricted set of cells such as macrophages, DCs and B cells. They present peptides derived from exogenous antigens, taken up via mechanisms such as endocytosis and phagocytosis. Antigenic peptides presented by MHC class II molecules are bound by TCRs expressed by CD4+ T cells. T cells represent a subset of lymphocytes that differentiate within the thymus, a small bi-lobular organ situated in the anterior mediastinum. Each T cell expresses a unique antigen-specific receptor (the TCR) with a unique recognition capacity. T cells do not directly recognise whole pathogens, but are only specifically activated by DCs transformed into APCs which present molecular fragments (mostly peptides derived from limited digestion of protein antigens) in association with MHC molecules at the cell surface. Naïve lymphocytes are therefore ‘blind’ to live microorganisms and need the help of APCs to adequately react to an invading pathogen. An individual naïve T cell can only be activated by a protein antigen for which it has a specific receptor, and which has been processed and presented by an APC. Cells activated by antigen-bearing DCs express the cluster of differentiation (CD)4 cell-surface protein, and are thus referred to as CD4+ T cells.

6) [1, 2]. Fakt ten jest niezwykle istotny z punktu widzenia diagnostyki autopsyjnej zarodków, bowiem rozpoznanie ubytku przegrody międzykomorowej w tym miejscu przed 8. tygodniem nie powinno być stawiane [30]. Przekształcanie

mięśnia komór dotyczy w okresie zarodkowym również samej jego struktury. Początkowo gąbczaste utkanie spowodowane jest brakiem tętnic wieńcowych i żył serca, a co za tym idzie, mięsień odżywiany jest na drodze dyfuzji (Ryc. 6) [10, 28]. Jak wspomniano na wstępie, kluczową www.selleckchem.com/products/abt-199.html rolę w rozwoju naczyń serca pełni narząd przednasierdziowy wywodzący się z tylnego pola sercowego. Komórki migrują zeń, tworząc dystalne odcinki tętnic wieńcowych, które dopiero na późniejszym etapie ulegają włączeniu w ścianę zatok aorty [10]. Co jest charakterystyczne, w większości przypadków, niezależnie od położenia aorty (jak np. w przełożeniu wielkich naczyń),

tętnice wieńcowe łączą się właśnie z nią, co stanowi istotny element diagnostyki przedoperacyjnej. W momencie zakończenia rozwoju naczyń serca miokardium ulega procesowi scalania, czyli kompakcji. Jego zaburzenia, zwykle niezależne od prawidłowego rozwoju tętnic wieńcowych, prowadzą do powstania kardiomiopatii gąbczastej (non-compaction cardiomyopathy) [30]. Zgodnie z podaną we wstępie informacją na temat zapętlania cewy sercowej, droga odpływu ulega wklinowaniu pomiędzy zastawki przedsionkowo-komorowe. Prawidłowe jej położenie jest zatem uwarunkowane nie tylko rotacją drogi odpływu, ale także procesem Linsitinib in vitro podziału kanału przedsionkowo-komorowego, co ma swoje odzwierciedlenie w wadach przegrody przedsionkowo-komorowej [25]. Droga see more odpływu poprzez worek aortalny i parzysty system łuków aortalnych zaopatrujących łuki gardłowe łączy się z dwiema aortami grzbietowymi (Ryc. 7). Sam worek aortalny daje początek dystalnej części aorty wstępującej, części łuku aorty i pniowi ramiennogłowowemu. Proksymalna część aorty wstępującej oraz pień płucny powstają z dalszej części stożka. Aby naczynia te odchodziły prawidłowo, tj. aorta z komory morfologicznie lewej, a pień płucny z komory morfologicznie prawej, musi dojść nie tylko do prawidłowej rotacji stożka,

ale i jego podziału [8, 12]. Dwa grzebienie aortalno-płucne wewnątrz stożka łączą się ze sobą i wraz z całym stożkiem ulegają spiralnemu skręceniu. Grzebienie te biorą również udział w rozwoju prawych i lewych płatków zastawek wielkich naczyń [1, 12]. Tylny płatek zastawki aortalnej i przedni zastawki pnia płucnego powstają z oddzielnych poduszeczek wsierdziowych. Prawidłowy łuk aorty i jego gałęzie rozwijają się na drodze przekształceń lewych łuków aortalnych: trzeciego i czwartego [31]. Przewód tętniczy, łączący cieśń aorty z pniem płucnym powstaje, podobnie jak dystalna część tego ostatniego, z szóstego lewego łuku aortalnego. Całokształt powyższych procesów prowadzi do powstania prawidłowo spiralnie skręconych naczyń, gdzie aorta odchodzi do tyłu i na prawo od pnia płucnego.

Financial support to K.Z. by the Austrian Science Foundation (FWF) (Project No. P24742) is gratefully acknowledged. E.S. thanks the Austrian Academy of Sciences for a DOCfFORTE

fellowship. “
“Although magnetic resonance Transmembrane Transporters modulator imaging (MRI) of the gas phase is possible without the use of hyperpolarized (hp) spin states [1], the density of gases at ambient pressure and temperature is typically reduced by about three orders of magnitude compared to the respective condensed phase. This significantly lowers Nuclear Magnetic Resonance (NMR) signal intensities and limits magnetic resonance imaging (MRI) resolution as the MRI experiments require gases with high gyromagnetic ratio, γ, high spin concentrations, and shorter longitudinal (T1) relaxation times (to allow for rapid signal averaging). Hp spin states, on the other hand, can enhance the NMR signals by many orders of magnitude compared to thermally polarized states and enable gas phase MRI of both dilute spin systems and nuclei with low gyromagnetic ratios. Since the hyperpolarization is almost always produced outside the MRI detection region, the hp gas typically requires some form of transport from the hyperpolarizer to the detection zone and sufficiently long relaxation times are needed to sustain the generated hyperpolarized state until NMR signal detection has

occurred. There is no disadvantage from slow T1 relaxation in hyperpolarized MRI because signal averaging is not based on relaxation recovery but on renewed delivery of hyperpolarized species for every scan. Unfortunately, most molecules PLX3397 nmr experience fast relaxation in the gas phase due to spin–rotation interactions. A noticeable exception is the group of mono-atomic noble gases where spin–rotation relaxation only occurs during short-lived interaction with other atoms [2]. Therefore T1 times of many hours and even days can be possible unless additional relaxation

mechanisms are present [2], [3], [4] and [5]. To date, the most widespread and successful MRI applications of hp noble gases utilize the isotope mafosfamide 3He (spin I = ½, NMR frequency 75.905 MHz at 2.35 T) for preclinical and clinical studies of pulmonary pathophysiology. A review of the successful applications with hp 3He MRI would exceed the purpose of this paper and is therefore best left to the specialists in this field (see for instance [6], [7] and [8] for previous reviews). Furthermore, the main supply source for 3He is tritium decay in nuclear (fusion) warheads with no viable current alternative in sight. The very high demand for this isotope for many types of applications has therefore led to a 3He supply crisis as evidenced by US congressional hearings [9]. The best remedies to this problem for the MR community may be rigorous 3He recycling whenever possible and the exploration of alternative techniques.

It should be noted that the last column in Table 1 represents Pictilisib mainly the cases when the dune toe does not move but the shoreline does (the opposite situation is extremely rare). Both Figure 10 and Table 1 show that there was no clear tendency in shoreline and dune toe dynamics during the study period. We can only speak about the slightly greater probabilities of events, when both lines are immobile or only one of them is moving (30–50%). Also, consistent (onshore or offshore) migration is slightly more likely

to happen (25–40%) than the divergent or convergent movements of both lines (25–35%). A more typical situation is when one line stays put while the other migrates. In such instances the migrating line is the shoreline, whose dynamics is usually dominant. Therefore, either erosion or accumulation is observed at shorter time scales, whereas in the long term the beach will remain in equilibrium. This therefore confirms that empirical observations and assessments of beach evolution CDK activity and condition

are time-scale dependent (Guillen et al. 1999). Under the natural conditions of a southern Baltic multi-bar dissipative shore, the coefficient of correlation R between the shoreline and dune toe displacements lies in wide ranges, from about 0 to 0.8 at a long-term time scale (25 years) and from about −0.4 to about 0.8 at a short-term scale (annual). Negative values of R in the annual analysis

mostly represent instantaneous situations of short but intensive storms during which the dune toe retreats and the sandy material from dune erosion is deposited on the beach, causing the shoreline to advance (accumulation). In the long run, such specific cases are dominated by more typical shore behaviour, namely, the evolution of the shoreline position only (small correlations between shoreline and dune toe motions) or the simultaneous movement of shoreline and dune toe in the same direction (high correlations). The latter occurs either during severe, prolonged storms, causing both the shoreline and the dune toe to retreat, or during long periods of weak wave impact, which are favourable to the accumulation of sand at the shoreline (onshore sediment transport) and at the dune toe (aeolian deposition). All the above response Ureohydrolase patterns of emerged coastal forms (shoreline with beach berm, dune) depend on features of the shoreface, e.g. on nearshore submerged forms (bars). The bar system is a kind of time- and space-variable energy filter, dissipating most of the wave energy during storms and allowing waves to cross undisturbed towards the shoreline in calmer periods. The most common situation (30–50% of all cases) is when waves are weak and moderate, when the dune toe is stable and the shoreline is subject to seaward or landward displacement, and is most frequently observed on a relatively wide beach.

tackled this problem by integration of MS, NMR, and IM-MS data [74] to characterize αB-crystallin, a small heat shock protein

(Fig. 4). MS data indicated that this system exists in a dynamic equilibrium of differently sized oligomers. NMR spectra revealed that each monomer exists in a symmetrical environment. A range of candidate structures was constructed formed by either series of regular polyhedra or rings. Computed collision cross-sections (CCS) of these models were compared to those obtained experimentally. Screening Library cell line Using the observed trends in CCS, consistent models of the dominant αB-crystallin 24-, 26- and 28-mer oligomers were identified as polyhedral architectures. These arrangements provide a structural rationale for the interconversion of these oligomers via loss and addition of a subunit. In a similar integrated approach atomic structures of 24-mer αB-crystallin complexes have been derived [75] and [76]. Lack of symmetry in a FG-4592 nmr complex also means a significant loss of information to drive the modeling. Thus studies on non-symmetrical complexes are typically limited to dock two subunits together, of which one may be a known, multi-subunit complex itself. Recent work of the Kay lab

focused on the interaction between the 70 kDa DnaK and the 580 kDa hexameric ClpB in protein disaggregation [77]. Using an impressive, and pragmatic, combination of backbone and methyl-group based TROSY and complexes with hexameric and monomeric

variants of ClpB, the authors could define the binding surfaces on both proteins from CSP measurements and identify a 1:6 stoichiometry of the DnaK:ClpB complex. PRE measurements were performed on complexes of ILVM-labeled DnaK nucleotide binding domain bound to monomeric ClpB, labeled with MTSL at five different positions. The resulting 29 distance restraints were combined with CSP-derived Staurosporine ic50 ambiguous interaction restraints to dock the DnaK-NBD to a ClpB monomer (Fig. 5). The models were validated by mutagenesis and used to devise functional test of ClpB–DnaK function in protein disaggregation, revealing that the DnaK–ClpB interaction stimulates ClpB activity on the substrate. A nice example of how different types of NMR data can be used comes from the docking of a nuclear export signal (NES) peptide to the 150 kDa exportin CRM1/RanGTP complex [42] and [78]. Using an intricate combination of 13C-direct detection, CRINEPT-TROSY, several ambiguous and unambiguous intermolecular NOEs and solvent PREs, the peptide was docked precisely and in a well-defined conformation to its binding site. The resulting structures were consistent with the crystal structure of the complex based on a NES-fusion protein and explained structural basis of NES recognition. As a large DNA–protein complex, nucleosomes present an additional challenge in modeling of their complexes with other chromatin factors.

That is a quite different thing, and I believe this is not just an irrelevant point. I believe that failure to recognise the difference has led to several failures of ‘coastal management’. Recognition of the important difference

would go a long way, in many cases, towards turning an intractable problem into a tractable one. I have seen several examples where recognition of this different focus of what the target of management really is, and the change in management which would arise logically from it, could lead to a shift in the way of working to solve it. I think there are many cases where recognition of this would have made an RGFP966 purchase impossible problem become a possible one. In the case of many systems, for example, the complexity of the system is high and its components cannot by any stretch of the imagination be ‘managed’. But the management of the human behaviour that is causing it to deteriorate, such as discharge of sewage or of uncontrolled dredging, is a simple task, at least in principle. A welcome shift towards this started some years ago, seen more often than not in phrases (including ‘mission statements’ in NGO brochures, for example) of the sort

“people are a part of the ecosystem too”. Indeed they are, in many cases that I have seen this is more meant to mean ‘don’t mess with people’s rights, traditions or long held customs’. Navitoclax order Well, traditional customs do have to change in many cases as populations rise and put unsustainable pressures on the supporting ecosystem. Not all customs should be or can be sustained in the modern world anyway – hunter-gathering was a long practiced tradition

until population rise forced a change to farming. Management of human behaviour as it impacts on our life support systems is what the focus should be. Trying to manage oxyclozanide the ecosystem to fit what we used to do simply is not working. There is a point in doing this, even if climate change is coming along and threatening to overwhelm some local impacts. We can buy time if we reduce some of the locally inflicted impacts on our local support ecosystem. Indeed we need to do so more effectively. Each report of the IPCC shows that, for many factors, the predictions of the previous IPCC report were too conservative. For an up to date example: the previous IPCC envelope for sea level rise (global average rise) was up to about a half metre by the end of this century. Since then, several uncertainties have been heavily researched, new results published, and the report next year should, if it reflects the new research, suggest that up to 1.9 or 2.0 m could be the upper end of the envelope. This is four times greater. Consider the implications to coastal societies, indeed to those dozens of countries whose entire estate lies just a couple of metres above present sea level.

1). REPC express ecto-5′-nucleotidase (CD73) and platelet-derived growth factor receptor β-polypeptide (PDGFRB),[9] and [13] both are also markers of pericytes and EPO-negative interstitial fibroblasts.14Epo expression in tubular epithelial cells appears to be suppressed by GATA transcription factors, in particular GATA-2 and GATA-3, and can be reactivated under normoxic

or hypoxic conditions when the GATA core consensus binding sequence upstream of the Epo transcription start site is mutated. 11 The kidney responds to hypoxia by increasing the number of REPC in an O2-dependent manner and therefore regulates EPO output through adjustments in REPC number. [8] and [11] O2-dependent Epo transcription is controlled by distinct regulatory DNA sequences. These Metformin flank the Epo coding sequence on both sides, the kidney-inducibility element Carfilzomib research buy in the 5′-region and the liver-inducibility element in the 3′-region. [15], [16] and [17] The 3′-hypoxia enhancer region is absolutely required for the hypoxic induction of Epo in the liver, as shown by genetic studies in mice. 18 REPC have been visualized

in BAC transgenic mice through the use of green fluorescent protein (GFP). In this transgenic model the Epo coding sequence was replaced by GFP cDNA, which brings GFP under the control of Epo regulatory elements. 11 GFP expression was found in renal peritubular interstitial cells and in a subpopulation of hepatocytes that were localized around the central vein, supporting the notion that these two cell types represent the major sites of physiologic EPO production under conditions of systemic hypoxia. In the kidney, GFP-positive interstitial cells were unique in their morphologic appearance,

as they displayed dendrite-like processes and expressed neuronal-specific markers, such as microtubule-associated protein 2 (MAP2) and neurofilament protein light polypeptide (NFL), indicating that REPC may be derived from progenitor cells of neuronal origin. This notion is furthermore supported by lineage tracing studies that utilized myelin protein zero (P0)-Cre transgenic mice, which express Cre-recombinase in neural crest-derived cells. 13 In keeping with this observation, Frede and colleagues 3-mercaptopyruvate sulfurtransferase established an EPO-producing renal tumor cell line with similar morphologic and molecular characteristics. 19 Although the hypoxic induction of Epo was reported in 4E cells, a mesenchymal cell clone with characteristics of embryonic kidney stromal cells, 20 primary REPC that retain their EPO-producing ability are difficult to culture. The molecular mechanisms underlying this phenomenon are unclear. Transdifferentiation of REPC into myofibroblasts, which are a main source of collagen in fibrotic kidneys, has been proposed as a potential mechanism by which REPC loose their ability to synthesize EPO in CKD ( Fig. 1).

PCP is a phenol derivative that has been extensively used as a wood preservative, insecticide and fungicide [7] and [8]. PCP undergoes oxidative dechlorination to form tetrachlorohydroquinone (TCHQ), a more toxic metabolite of PCP [9] and [10]. PCP toxicity seems to be related mainly to TCHQ-mediated uncoupling of oxidative phosphorylation and the generation of reactive oxygen species (ROS) in mitochondria [11] and [12]. Although it has been shown to promote tumour growth [13], studies suggesting that this compound and its derivative can induce cell death are sparse [14] and [15]. This work was initiated by our preliminary

observations that PCP induces inhibition of CK2 in an ATP-competitive manner. The aim of this study was http://www.selleckchem.com/products/ipi-145-ink1197.html to contribute to the knowledge of the effects of PCP in human pancreatic cancer cells and to shed light on the intracellular signalling pathways involved in PCP-induced cytotoxicity. To our knowledge, this is the first contribution on the characterization of PCP at the molecular level in this type of cells. Protein kinase activity measurements of recombinant CK2α and CK2α2β2 were performed in 40 μl of a reaction mixture containing varying concentrations of C11, PCP or dimethylallylamine (DMA), as indicated in the figure legends, 25 mM Tris/HCl pH 7.5,

5 mM NaCl for CK2α and 150 mM for CK2α2β2, 18.75 mM MgCl2, 0.5 mM DTT, 190 μM synthetic peptide RRRDDDSDDD (KinaseDetect, Odense, Denmark), 125 μM ATP and 10 μCi [γ-32P-ATP] (3000 Ci/mmol, Akt inhibitor Hartmann Analytic, Braunschweig, Germany). After incubation at 30 °C for 10 min, the reactions were stopped on ice and samples were spotted onto a grade P81 cellulose paper (WhatmanTM, GE Healthcare, Brøndby, Denmark). Radioactivity incorporated into the substrate target was determined by scintillation counting in a 1450 MicroBeta2 Plate counter (PerkinElmer, Waltham, MA, USA). The pancreatic ductal adenocarcinoma cell lines Panc-1 and MIA PaCa-2 (ATCC,

Rockville, MD, USA) were cultured according to the manufacturer’s guidelines and maintained at 37 °C in Oxalosuccinic acid a humidified atmosphere supplemented with 5% CO2. Cells were treated with C11 (NCI, Bethesda, MD, USA), pentachlorophenol (PCP, AccuStandard, New Haven, CT, USA), dimethylallylamine (DMA, Chemical point, Deisenhofen, Germany) and TNFα (R&D Systems, Abingdon, United Kingdom) as indicated in the figure legends. DMSO (Sigma-Aldrich, Schnelldorf, Germany) was used in all control experiments at a final concentration not exceeding 0.2% (v/v). Cell viability was determined by the WST-1 assay (Roche, Mannheim, Germany) in a 96-well plate. 24 h after seeding, cells were treated with various concentrations of C11, PCP and DMA, respectively, for 48 h. WST-1 reagent was added to the cells according to the manufacturer’s instructions and cell viability was determined 2 h later in a VersaMax ELISA microplate reader (Molecular Devices, CA, USA).