Many faces of DAMPs in cancer therapy

A new concept of immunogenic cell death (ICD) has recently been proposed. The immunogenic characteristics of this cell death mode are mediated mainly by molecules called ‘damage-associated molecular patterns’ (DAMPs), most of which are recognized by pattern recognition receptors. Some DAMPs are actively emitted by cells undergoing ICD (e.g. calreticulin (CRT) and adenosine triphosphate (ATP)), whereas others are emitted passively (e.g. high-mobility group box 1 protein (HMGB1)). Recent studies have demonstrated that these DAMPs play a beneficial role in anti-cancer therapy by interacting with the immune system. The molecular pathways involved in translocation of CRT to the cell surface and secretion of ATP from tumor cells undergoing ICD are being elucidated. However, it has also been shown that the same DAMPs could contribute to progression of cancer and promote resistance to anticancer treatments. In this review, we will critically evaluate the beneficial and detrimental roles of DAMPs in cancer therapy, focusing mainly on CRT, ATP and HMGB1

Alle har en historie at bygge, fortælle, gengive og skrive LEGO som læringsværktøj

Til skolesystemer verden over har LEGO Education introduceret etnyt læringsværktøj, StoryStarter, som [...

Anodal transcranial direct current stimulation increases corticospinal excitability, while performance is unchanged

Anodal transcranial direct current stimulation (a-tDCS) has been shown to improve bicycle time to fatigue (TTF) tasks at 70–80% of VO(2max) and downregulate rate of perceived exertion (RPE). This study aimed to investigate the effect of a-tDCS on a RPE-clamp test, a 250-kJ time trial (TT) and motor evoked potentials (MEP). Twenty participants volunteered for three trials; control, sham stimulation and a-tDCS. Transcranial magnetic stimulation was used to determine the corticospinal excitability for 12 participants pre and post sham stimulation and a-tDCS. The a-tDCS protocol consisted of 13 minutes of stimulation (2 mA) with the anode placed above the Cz. The RPE-clamp test consisted of 5 minutes ergometer bicycling at an RPE of 13 on the Borg scale, and the TT consisted of a 250 kJ (∼10 km) long bicycle ergometer test. During each test, power output, heart rate and oxygen consumption was measured, while RPE was evaluated. MEPs increased significantly by 36% (±36%) post a-tDCS, with 8.8% (±31%) post sham stimulation (p = 0.037). No significant changes were found for any parameter at the RPE-clamp or TT. The lack of improvement may be due to RPE being more controlled by afferent feedback during TT tests than during TTF tests. Based on the results of the present study, it is concluded that a-tDCS applied over Cz, does not enhance self-paced cycling performance

ENERGY LEVEL AND STRATEGY OF FEEDING FOR DAIRY COWS IN THE DRY PERIOD

Djelovanje strategije hranidbe u suhostaju na proizvodnju i zdravlje istaživalo se u dva pokusa što su obuhvatila 80 i 96 mliječnih krava. U pokusu br. 1 ispitivalo se djelovanje razine energije (normalna i visoka (1.5 x N) i djelovanje dnevnog sagorjevanja kratkolančanih masnih kiselina (KLMK) u preživača (+ i -) u zadnja četiri tjedna suhostaja. U pokusu br. 2 uključeno je samo sagorjevanje KLMK. Šesnaest je krava zaklano radi ruminalnog pregleda. Sagorjevanje KLMK je inducirano davanjem 4.5 kg ječma u jutro i kabaste hrane (roughage) na večer. Nakon telenja koncentracija je postepeno povećavana do razine od 9 kg ST a sliaža trave bila ad lib. u obje skupine. Sagorjevanje KLMK povećalo je uzimanje silaže trave u prvih pet tjedana post parfum u pokusu br. 1, ali ne u pokusu br. 2. U pokusu br. 1 postojalo je međusobno djelovanje između razine hranjena i sagorjevanja KLMK na proizvodnju mlijeka, dok u pokusu br. 2 nije primijenjena nikakva razlika. U krava s pojačanim sagorjevanjem KLMK došlo je do rjeđe pojave ketoze i probavnih smetnji u prvom pokusu ali ne u drugom, te je postojala tendencija povećanja aktivnosti u mukozi rumena, no bez makroskopskih razlika. Zaključeno je da se sagorjevanjem KLMK ne postiže nikakvo ili samo neznatno pozitivno djelovanje u suhostaju na uzimanje hrane, proizvodnju, zdravlje i reprodukciju.The effect of feeding strategy in the dry period on performance and health was investigated in two experiments comprising 80 and 96 dairy cows. In exp. 1 the effect of energy level (Normal and High (1.5 x N) and the effect of a daily ruminal SCFA-burst (+ and -) in the last 4 weeks of the dry period were examined. In exp. 2. only SCFA-burst was included. Sixteen cows were slaughtered for ruminal examination. SCFA-burst was induced by allocating 4.5 kg barley in the morning and roughage in the evening. After calving concentrate was gradually increased to a level of 9 kg DM and grass silage was ad. lib in all groups. The SCFA-burst increased grass silage intake in the first 5 weeks post partum in exp. 1 but not in exp. 2. In exp. I there was an interaction between feeding level and SCFA-burst on milk production, while no difference between treatments were seen in exp. 2. The SCFA bursted cows had a lover incidence of ketose and digestive disorders in the first experiment but not in the second, and there was a tendency to increased activity in the ruminal mucosa but without any macroscopical differences. It is concluded that none or only small benefits are obtained from SCFA- bursts in the dry period on feed intake, performance, health, and reproduction

Defining solute carrier transporter signatures of murine immune cell subsets

Solute carrier (SLC) transporters are membrane-bound proteins that facilitate nutrient transport, and the movement across cellular membranes of various substrates ranging from ions to amino acids, metabolites and drugs. Recently, SLCs have gained increased attention due to their functional linkage to innate immunological processes such as the clearance of dead cells and anti-microbial defense. Further, the druggable nature of these transporters provides unique opportunities for improving outcomes in different immunological diseases. Although the SLCs represent the largest group of transporters and are often identified as significant hits in omics data sets, their role in immunology has been insufficiently explored. This is partly due to the absence of tools that allow identification of SLC expression in particular immune cell types and enable their comparison before embarking on functional studies. In this study, we used publicly available RNA-Seq data sets to analyze the transcriptome in adaptive and innate immune cells, focusing on differentially and highly expressed SLCs. This revealed several new insights: first, we identify differentially expressed SLC transcripts in phagocytes (macrophages, dendritic cells, and neutrophils) compared to adaptive immune cells; second, we identify new potential immune cell markers based on SLC expression; and third, we provide user-friendly online tools for researchers to explore SLC genes of interest (and the rest of the genes as well), in three-way comparative dot plots among immune cells. We expect this work to facilitate SLC research and comparative transcriptomic studies across different immune cells

Nitrogen and sulphur management: challenges for organic sources in temperate agricultural systems

A current global trend towards intensification or specialization of agricultural enterprises has been accompanied by increasing public awareness of associated environmental consequences. Air and water pollution from losses of nutrients, such as nitrogen (N) and sulphur (S), are a major concern. Governments have initiated extensive regulatory frameworks, including various land use policies, in an attempt to control or reduce the losses. This paper presents an overview of critical input and loss processes affecting N and S for temperate climates, and provides some background to the discussion in subsequent papers evaluating specific farming systems. Management effects on potential gaseous and leaching losses, the lack of synchrony between supply of nutrients and plant demand, and options for optimizing the efficiency of N and S use are reviewed. Integration of inorganic and organic fertilizer inputs and the equitable re-distribution of nutrients from manure are discussed. The paper concludes by highlighting a need for innovative research that is also targeted to practical approaches for reducing N and S losses, and improving the overall synchrony between supply and demand

Vaccination with Necroptotic Cancer Cells Induces Efficient Anti-tumor Immunity

SummarySuccessful immunogenic apoptosis in experimental cancer therapy depends on the induction of strong host anti-tumor responses. Given that tumors are often resistant to apoptosis, it is important to identify alternative molecular mechanisms that elicit immunogenic cell death. We have developed a genetic model in which direct dimerization of FADD combined with inducible expression of RIPK3 promotes necroptosis. We report that necroptotic cancer cells release damage-associated molecular patterns and promote maturation of dendritic cells, the cross-priming of cytotoxic T cells, and the production of IFN-γ in response to tumor antigen stimulation. Using both FADD-dependent and FADD-independent RIPK3 induction systems, we demonstrate the efficient vaccination potential of immunogenic necroptotic cells. Our study broadens the current concept of immunogenic cell death and opens doors for the development of new strategies in cancer therapy