Reactive Oxygen and Nitrogen Species in Defense/Stress Responses Activated by Chitosan in Sycamore Cultured Cells

Chitosan (CHT) is a non-toxic and inexpensive compound obtained by deacetylation of chitin, the main component of the exoskeleton of arthropods as well as of the cell walls of many fungi. In agriculture CHT is used to control numerous diseases on various horticultural commodities but, although different mechanisms have been proposed, the exact mode of action of CHT is still unknown. In sycamore (Acer pseudoplatanus L.) cultured cells, CHT induces a set of defense/stress responses that includes production of H₂O₂ and nitric oxide (NO). We investigated the possible signaling role of these reactive molecules in some CHT-induced responses by means of inhibitors of production and/or scavengers. The results show that both reactive nitrogen and oxygen species are not only a mere symptom of stress conditions but are involved in the responses induced by CHT in sycamore cells. In particular, NO appears to be involved in a cell death form induced by CHT that shows apoptotic features like DNA fragmentation, increase in caspase-3-like activity and release of cytochrome c from the mitochondrion. On the contrary, reactive oxygen species (ROS) appear involved in a cell death form induced by CHT that does not show these apoptotic features but presents increase in lipid peroxidation.     

Milk from cows fed a diet with a high forage:concentrate ratio improves inflammatory state,oxidative stress,and mitochondrial function in rats

Excessive energy intake may evoke complex biochemical processes characterized by inflammation, oxidative stress, and impairment of mitochondrial function that represent the main factors underlying noncommunicable diseases. Because cow milk is widely used for human nutrition and in food industry processing, the nutritional quality of milk is of special interest with respect to human health. In our study, we analyzed milk produced by dairy cows fed a diet characterized by a high forage:concentrate ratio (high forage milk, HFM). In view of the low n-6:n-3 ratio and high content of conjugated linoleic acid of HFM, we studied the effects of this milk on lipid metabolism, inflammation, mitochondrial function, and oxidative stress in a rat model. To this end, we supplemented for 4 wk the diet of male Wistar rats with HFM and with an isocaloric amount (82 kJ, 22 mL/d) of milk obtained from cows fed a diet with low forage:concentrate ratio, and analyzed the metabolic parameters of the animals. Our results indicate that HFM may positively affect lipid metabolism, leptin:adiponectin ratio, inflammation, mitochondrial function, and oxidative stress, providing the first evidence of the beneficial effects of HFM on rat metabolism.     

Measurement of solid fat content by ultrasonic reflectance in model systems and chocolate

A series of confectionery coating fat (CCF) and cocoa butter (CB) dispersions in corn oil were prepared and tempered to a range of temperatures (10, 12 and 15 °C and 26, 27.5 and 29 °C respectively) to produce samples with solid fat contents (SFC) between 0 and 9%. The ultrasonic velocity in the CCF samples increased with increasing SFC and decreased with temperature, however the CB samples were too attenuating to allow velocity measurements. The ultrasonic reflectance at the surface of both sets of dispersions decreased linearly with SFC but at the same level of solids was less for CB than CCF suggesting some dependence on other aspects of fat structure. The microstructures and thermal properties of the fat systems are compared in an attempt to understand these structural differences. Finally ultrasonic reflectance is shown to respond to changes in a chocolate melt during tempering.     

The Strategic Control of Multiple Routes in Imitation of Actions.

The aim of this study was to bring to the surface the strategic use of imitative processes in the context of a 2-route model: (a) direct imitation, used in reproducing new, meaningless actions, and (b) imitation based on stored semantic knowledge of familiar meaningful actions. Three experiments were carried out with healthy participants who reproduced meaningful and meaningless actions within an established time limit. The study investigated 3 factors that could potentially affect the selection of processes used for imitation: (a) the composition of the experimental list (blocked or mixed presentation), (b) the presence-absence of instructions (Experiments 1 and 2), and (c) the relative proportions of the stimuli (Experiment 3). Overall, the results suggest that each of these factors influences the selection of imitative strategies in healthy individuals with temporarily reduced capacities, as happens in the case of brain-damaged patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Molecular Aspects and Prognostic Significance of Microcalcifications in Human Pathology: A Narrative Review

The presence of calcium deposits in human lesions is largely used as imaging biomarkers of human diseases such as breast cancer. Indeed, the presence of micro- or macrocalcifications is frequently associated with the development of both benign and malignant lesions. Nevertheless, the molecular mechanisms involved in the formation of these calcium deposits, as well as the prognostic significance of their presence in human tissues, have not been completely elucidated. Therefore, a better characterization of the biological process related to the formation of calcifications in different tissues and organs, as well as the understanding of the prognostic significance of the presence of these calcium deposits into human tissues could significantly improve the management of patients characterized by microcalcifications associated lesions. Starting from these considerations, this narrative review highlights the most recent histopathological and molecular data concerning the formation of calcifications in breast, thyroid, lung, and ovarian diseases. Evidence reported here could deeply change the current point of view concerning the role of ectopic calcifications in the progression of human diseases and also in the patients’ management. In fact, the presence of calcifications can suggest an unfavorable prognosis due to dysregulation of normal tissues homeostasis.     

Complementary Effects of Carbamylated and Citrullinated LL37 in Autoimmunity and Inflammation in Systemic Lupus Erythematosus

LL37 acts as T-cell/B-cell autoantigen in Systemic lupus erythematosus (SLE) and psoriatic disease. Moreover, when bound to “self” nucleic acids, LL37 acts as “danger signal,” leading to type I interferon (IFN-I)/pro-inflammatory factors production. T-cell epitopes derived from citrullinated-LL37 act as better antigens than unmodified LL37 epitopes in SLE, at least in selected HLA-backgrounds, included the SLE-associated HLA-DRB1*1501/HLA-DRB5*0101 backgrounds. Remarkably, while “fully-citrullinated” LL37 acts as better T-cell-stimulator, it loses DNA-binding ability and the associated “adjuvant-like” properties. Since LL37 undergoes a further irreversible post-translational modification, carbamylation and antibodies to carbamylated self-proteins other than LL37 are present in SLE, here we addressed the involvement of carbamylated-LL37 in autoimmunity and inflammation in SLE. We detected carbamylated-LL37 in SLE-affected tissues. Most importantly, carbamylated-LL37-specific antibodies and CD4 T-cells circulate in SLE and both correlate with disease activity. In contrast to “fully citrullinated-LL37,” “fully carbamylated-LL37” maintains both innate and adaptive immune-cells’ stimulatory abilities: in complex with DNA, carbamylated-LL37 stimulates plasmacytoid dendritic cell IFN-α production and B-cell maturation into plasma cells. Thus, we report a further example of how different post-translational modifications of a self-antigen exert complementary effects that sustain autoimmunity and inflammation, respectively. These data also show that T/B-cell responses to carbamylated-LL37 represent novel SLE disease biomarkers.     

CYP154C5 Regioselectivity in Steroid Hydroxylation Explored by Substrate Modifications and Protein Engineering**

CYP154C5 from Nocardia farcinica is a P450 monooxygenase able to hydroxylate a range of steroids with high regio- and stereoselectivity at the 16α-position. Using protein engineering and substrate modifications based on the crystal structure of CYP154C5, an altered regioselectivity of the enzyme in steroid hydroxylation had been achieved. Thus, conversion of progesterone by mutant CYP154C5 F92A resulted in formation of the corresponding 21-hydroxylated product 11-deoxycorticosterone in addition to 16α-hydroxylation. Using MD simulation, this altered regioselectivity appeared to result from an alternative binding mode of the steroid in the active site of mutant F92A. MD simulation further suggested that the entrance of water to the active site caused higher uncoupling in this mutant. Moreover, exclusive 15α-hydroxylation was observed for wild-type CYP154C5 in the conversion of 5α-androstan-3-one, lacking an oxy-functional group at C17. Overall, our data give valuable insight into the structure–function relationship of this cytochrome P450 monooxygenase for steroid hydroxylation.     

Open to a Select Few? Matching Partners and Knowledge Content for Open Innovation Performance

The purpose of the paper is to illuminate the costs and benefits of crossing firm boundaries in inbound open innovation (OI) by determining the relationships among partner types, knowledge content and performance. The empirical part of the study is based on a survey of OI collaborations answered by R&D managers in 415 Italian, Finnish and Swedish firms. The results show that the depth of collaboration with different partners (academic/consultants, value chain partners, competitors and firms in other industries) is positively related to innovation performance, whereas the number of different partners and size have negative effects. The main result is that the knowledge content of the collaboration moderates the performance outcomes and the negative impact of having too many different kinds of partners. This illustrates how successful firms use selective collaboration strategies characterized by linking explorative and exploitative knowledge content to specific partners, to leverage the benefits and limit the costs of knowledge boundary crossing processes.