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Plastic debris represents a contemporary point of concern for the marine environment, being discharged into the ocean at an alarming scale. However, the quantity of waste that is found in the ocean is unknown. Where does this waste come from, and where does it end up are questions that scientists and researchers are still trying to accurately answer. The majority of plastic products that make their way into the ocean come mainly from human activities. Most of them land on beaches, and eventually find their way into the ocean, being washed away by waves and tides. To assess the impact of these pollutants that are found in the marine environment, it is necessary to determine the concentration of the chemicals accumulating in the biomass, and the effects they cause. There are numerous biological effects which lead to many obvious diseases in marine species. Also, these harmful effects determine changes in community structure, the modification of the habitat and local or complete extinction of many aquatic species. This review aims to lay out the present situation of the marine environment, and the effects of the pollution caused by industrialization and urbanization. Different types of remediation approaches have been discussed, such as physical remediation techniques. Besides that, the role of numerous bacteria and fungi that are capable of breaking down these chemicals that surround us, has been highlighted and point at some of the bioremediation technologies that are currently available.

Ultraviolet B (UVB) radiation induces mutagenic DNA photoproducts, in particular cyclobutane pyrimidine dimers (CPDs), in epidermal keratinocytes (KC). To prevent skin carcinogenesis, these DNA photoproducts must be removed by nucleotide excision repair (NER) or apoptosis. Here we report that the UVB-sensitive transcription factor aryl hydrocarbon receptor (AHR) attenuates the clearance of UVB-induced CPDs in human HaCaT KC and skin from SKH-1 hairless mice. Subsequent RNA interference and inhibitor studies in KC revealed that AHR specifically suppresses global genome but not transcription-coupled NER. In further experiments, we found that the accelerated repair of CPDs in AHR-compromised KC depended on a modulation of the p27 tumor suppressor protein. Accordingly, p27 protein levels were increased in AHR-silenced KC and skin biopsies from AHR−/− mice, and critical for the improvement of NER. Besides increasing NER activity, AHR inhibition was accompanied by an enhanced occurrence of DNA double-strand breaks triggering KC apoptosis at later time points after irradiation. The UVB-activated AHR thus acts as a negative regulator of both early defense systems against carcinogenesis, NER and apoptosis, implying that it exhibits tumorigenic functions in UVB-exposed skin. In fact, AHR−/− mice developed 50% less UVB-induced cutaneous squamous cell carcinomas in a chronic photocarcinogenesis study than their AHR+/+ littermates. Taken together, our data reveal that AHR influences DNA damage-dependent responses in UVB-irradiated KC and critically contributes to skin photocarcinogenesis in mice.

While interorganizational research has emphasized the role of governance mechanisms in managing the performance of suppliers that provide critical input components, scholarship consistently assumes...

We explore the varying effects of contracts on blatant and lawful buyer opportunism. Building on contradicting findings on the effects of contracts on opportunism, we analyze contractual effects on...

The antimicrobial peptide murine β-defensin-14 (mBD14) was found to exert, in addition to its antimicrobial activity, the capacity to induce regulatory T cells as demonstrated in the model of contact hypersensitivity. Because it is induced by ultraviolet radiation, mBD14 may contribute to the antigen-specific immunosuppression by ultraviolet radiation. To prove whether this applies also for other immunologic models and because ultraviolet radiation appears to have beneficial effects on multiple sclerosis, we utilized the model of experimental autoimmune encephalomyelitis. Injection of mBD14 into mice before immunization with myelin oligodendrocyte glycoprotein caused amelioration of the disease with less central nervous system inflammation and decreased levels of proinflammatory cytokines and cytotoxic T cells. The beneficial effect was due to Foxp3 + regulatory T cells because it was lost on in vivo depletion of regulatory T cells. mBD14, however, also acts in a therapeutic setting, because injection of mBD14 into mice with clinical features of experimental autoimmune encephalomyelitis reduced the clinical score significantly. Human β-defensin-3, the human orthologue of mBD14, induced in vitro regulatory T cell-specific markers in CD4 + CD25 − T cells, shifting these nonregulatory cells into a regulatory phenotype with suppressive features. Thus, defensins may represent candidates worth being further pursued for the therapy of multiple sclerosis.

BACKGROUND Preterm infants are at risk of oxidative stress from neonatal intensive care interventions. 8-Oxo-2'-deoxyguanosine (8-oxodG), generated by oxygen radical attack on DNA, is a potential marker of oxidative stress. The aim of the present study was to investigate the impact of quality and source of enteral nutrition (EN) on renal excretion of 8-oxodG in preterm infants. METHODS Spontaneous urine samples were collected on postnatal days 26-31 in 33 preterm infants. Infants were fed either breast milk (BM), formula (FM), or BM/FM mixtures. Daily iron (Fe) supplementation was started day 28 ± 1 postnatally. 8-oxodG was determined by highperformance liquid chromatography-electrochemical detection (HPLC-EC). RESULTS The 8-oxodG/creatinine ratio was significantly higher in infants fed FM vs FM/BM (38.7 ± 28.7 vs 16.7 ± 12.2 nmol 8-oxodG/mmol creatinine, P < 0.0001) or BM (11.6 ± 10.4 nmol 8-oxodG/mmol creatinine, P < 0.0001). There was no significant effect of Fe supplementation (P = 0.547). 8-OxodG excretion showed significant interindividual variation but was similar within pairs of twins. CONCLUSION Quality and source of EN seem to influence oxidative stress in preterm infants. The underlying pathophysiological mechanism is unclear and needs further investigation. It may be speculated that other mechanisms than Fe supplementation contribute to oxidative stress, such as cow's milk protein-mediated up-regulation of the intestinal inflammatory cascade.

Disturbance of the epidermal barrier by UVR is associated with the release of antimicrobial peptides and inflammatory cytokines for the purpose of a danger response. On the other hand, UVR causes immunosuppression via regulatory T cells (Treg) that limit the inflammatory reaction. The concurrent induction of antimicrobial peptides and Treg by UVR may represent a counter-regulatory mechanism in response to barrier disruption, preventing microbial superinfection and sensitization to contact allergens, respectively, both of which cross impaired epidermis more easily. Thus, using a model of murine contact hypersensitivity we examined if disruption of the epidermal barrier only initiates similar counter-regulatory mechanisms via the generation of Treg. Sensitization through tape-stripped skin induced a weaker contact hypersensitivity response than in control mice. This was due to the induction of antigen-specific Treg, as demonstrated in adoptive transfer and depletion experiments utilizing DEREG mice. Treg induction by tape stripping was linked to the expression of the alarmin IL-33, as blockade of IL-33 exacerbated contact hypersensitivity, whereas injection of IL-33 inhibited contact hypersensitivity and induced Treg. These results demonstrate that epidermal barrier disruption, in addition to danger signals, induces regulatory events that prevent exaggerated skin inflammation and that IL-33 appears to be critically involved in this process.

In this paper we investigate the determinants of choosing minority alliances over joint ventures, suggesting that – while both are forms of equity alliances – they offer different governance advant...

Solar/ultraviolet (UV) radiation exerts a variety of biological effects, including suppression of the immune system. UV-induced immunosuppression is induced by suberythemogenic/physiological UV doses, and it affects primarily T-cell driven immune reactions. Another characteristic feature of UV-induced immunosuppression is its antigen-specificity. This is due to the induction of T cells with suppressive features, called regulatory T cells. Since UV-induced regulatory T cells may harbor therapeutic potential phenotypic and functional characterization of these cells is ongoing. Most of these studies have been performed in the murine model of contact hypersensitivity. In this protocol we describe a method for the UV-induced suppression of the induction of contact hypersensitivity and the adoptive transfer of immune response.

We have recently shown that topical application of sodium butyrate (SB) suppresses allergic contact dermatitis in mice. This effect was associated with the induction/activation of Treg, the activity of which is diminished in certain inflammatory dermatoses. To further study the effects of SB in chronic inflammatory skin disorders, we utilized the imiquimod (IMQ)-induced psoriasis-like skin inflammation model. Mice were treated with 5% IMQ cream (Aldarau00ae) on the shaved backs and ears for 10 days. One group of IMQ-treated mice received topically on the back skin 100 u00b5l of a 1 mM solution SB for 3 days. IMQ-treated mice developed thickening of the skin, erythema, scales as well as acanthosis, hyperkeratosis and inflammatory infiltrates. These inflammatory responses were significantly reduced upon administration of SB. On the RNA level, SB treatment leads to significant downregulation of Il17 transcription. In turn, transcription of Il10 was remarkably induced by SB. We surmise Treg to be the primary source of IL-10 which was supported by the upregulation of the mRNA of the Treg-specific transcription factor FOXP3. Together, these data support our assumption that SB might activate cutaneous Treg and thereby contribute to the downregulation of the inflammatory response. Though only topically applied, IMQ induces also systemic immunologic alterations. The number of IL-17-expressing CD45+ cells obtained from lymph nodes and spleens was remarkably enhanced in IMQ-treated mice, implying that the splenomegaly observed in IMQ treated mice may be in part due to the infiltration/expansion of IL-17+ lymphocytes. This effect was almost completely prevented by SB. In addition, significantly fewer CD45+ cells expressing FOXP3 and IL-10 were detected after IMQ administration, suggesting downregulation of Treg. Together, this implies that IMQ suppresses Treg and activates IL-17-expressing lymphocytes an effect which can be dramatically reversed by SB, explaining the beneficial effect of SB on the resolution of the IMQ-induced psoriasis-like lesions.

There is evidence that gut commensal microbes affect the mucosal immune system via expansion of regulatory T cells (Tregs) in the colon. This is mediated via short-chain fatty acids, bacterial metabolites generated during fiber fermentation, which include butyrate, propionate, and acetate. We postulated that short-chain fatty acids produced by commensal skin bacteria may also activate resident skin Tregs, the activity of which is diminished in certain inflammatory dermatoses. Sodium butyrate (SB) either injected subcutaneously or applied topically onto the ears of hapten-sensitized mice significantly reduced the contact hypersensitivity reaction. This effect was histone acetylation-dependent because suppression was abrogated by anacardic acid, a histone acetyltransferase inhibitor. The genes encoding for the Treg-specific transcription factor foxp3 and for IL-10 were up-regulated upon treatment with sodium butyrate, as determined by quantitative real-time reverse transcription-PCR. Immunofluorescence analysis showed enhanced numbers of Foxp3-positive cells in sodium butyrate-treated skin. Additionally, CD4+CD25– nonregulatory human T cells exerted suppressive features upon incubation with sodium butyrate. This indicates that Tregs can be induced by short-chain fatty acids, suggesting (i) that resident skin microbes may prevent exaggerated inflammatory responses by exerting a down-regulatory function and thereby maintaining a stable state under physiologic conditions and (ii) that short-chain fatty acids may be used therapeutically to mitigate inflammatory skin reactions.

Firms often both make and buy the same input, a strategy termed concurrent sourcing. The phenomenon has been documented in different organizational contexts from industrial purchasing, innovation s...