Alpha1-acid glycoprotein post-translational modifications: a comparative two dimensional electrophoresis based analysis

Alpha1-acid glycoprotein (AGP) is an immunomodulatory protein expressed by hepatocytes in response to the systemic reaction that follows tissue damage caused by inflammation, infection or trauma. A proteomic approach based on two dimensional electrophoresis, immunoblotting and staining of 2DE gels with dyes specific for post-translational modifications (PTMs) such as glycosylation and phosphorylation has been used to evaluate the differential interspecific protein expression of AGP purified from human, bovine and ovine sera. By means of these techniques, several isoforms have been identified in the investigated species: they have been found to change both with regard to the number of isoforms expressed under physiological condition and with regard to the quality of PTMs (i.e. different oligosaccharidic chains, presence/absence of phosphorilations). In particular, it is suggested that bovine serum AGP may have one of the most complex pattern of PTMs among serum proteins of mammals studied so far

Protein biomarkers as indicator for water pollution in some lagoons of Sardinia (Italy)

1 - Studying the expressed proteome in mussel tissues is important to understand many different biological, physiological and ecological aspects that may be of advantage in shellfish rearing, encompassing growth cycle, food safety and traceability as well as understanding the biological effects of environmental pollution and climate change.2 - The present work attempted to accomplish a systematic characterization of the foot muscle proteome of M. galloprovincialis, to gather data about its variability in physiological conditions occurring in different environments of mussel rearing and to identify a putative set of protein biomarkers that may be significantly correlated to environmental factors.3 - A total of 360 mussels were sampled from three different lagoons of Sardinia, each one characterized by its different environmental and ecological system. According to a double latin square design, a smaller subgroup of 54 mussels that was representative of the original population was submitted to proteomics analysis and trace metals quantification. Classical and multivariate statistics was performed to correlate protein expression data to trace metal content and to environmental parameters recorded in situ.4 - A protein expression pattern of 79 protein was identified as related to the response to environmental stressors like dissolved oxygen, water acidity, temperature and trace metals.5 - The identified proteins are cytoskeletal proteins (α-tubulin, β-tubulin, myosin light chains and tropomyosin) or are involved in metabolic pathways (fructose bisphosphate aldolase), in energy pathways (cytosolic malate dehydrogenase and arginine kinase), in antioxidant defense (protein disulfide isomerase) and in protein turnover (different isoforms of the heat shock proteins Hsp70 and Hsc71); also the histone protein H2B is reported.6 - Our preliminary results show that there is correlation between the expressed protein pattern and the environmental conditions, confirming the findings of other proteomics works carried out on different mussel tissues and other marine invertebrates. Further validation procedures of the identified correlations must be accomplished in order to regard the identified proteins as biomarkers for environmental pollution and climate chang

Nanotechnology and its applications in food and animal science

Nanotechnology has the potential to manipulate matter at the nanometre scale, creating and assembling substances at a molecular level with new and interesting properties. This has offered opportunities for applications in different sectors. Recently, nanotechnology has received particular attention due to its promising applications in animal nutrition, drugs and nutrients delivery, animal reproduction, disease diagnosis and treatment. In the food sector, nanotechnology is applied to the improvement of food packaging, processing, monitoring and the development of food with new functional properties that can respond to the needs of consumers. This review will focus on the advances of nanotechnology in food sector and animal science with particular attention to animal nutrition. The implications for safety and regulation will be also discussed

Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes.

Immune checkpoints refer to a plethora of inhibitory pathways of the immune system that play a crucial role in maintaining self-tolerance and in tuning the duration and amplitude of physiological immune responses to minimize collateral tissue damages. The breakdown of this delicate balance leads to pathological conditions, including cancer. Indeed, tumor cells can develop multiple mechanisms to escape from immune system defense, including the activation of immune checkpoint pathways. The development of monoclonal antibodies, targeting inhibitory immune checkpoints, has provided an immense breakthrough in cancer therapy. Immune checkpoint inhibitors (ICI), initially developed to reverse functional exhaustion in T cells, recently emerged as important actors in natural killer (NK)-cell-based immunotherapy. Moreover, the discovery that also helper innate lymphoid cells (ILCs) express inhibitory immune checkpoints, suggests that these molecules might be targeted on ILCs, to modulate their functions in the tumor microenvironment. Recently, other strategies to achieve immune checkpoint blockade have been developed, including miRNA exploiting systems. Herein, we provide an overview of the current knowledge on inhibitory immune checkpoints on NK cells and ILCs and we discuss how to target these innate lymphocytes by ICI in both solid tumors and hematological malignancies

Different features of tumor-associated NK cells in patients with low-grade or high-grade peritoneal carcinomatosis

Peritoneal carcinomatosis (PC) is a rare disease defined as diffused implantation of neoplastic cells in the peritoneal cavity. This clinical picture occurs during the evolution of peritoneal tumors, and it is the main cause of morbidity and mortality of patients affected by these pathologies, though cytoreductive surgery with heated intra-peritoneal chemotherapy (CRS/HIPEC) is yielding promising results. In the present study, we evaluated whether the tumor microenvironment of low-grade and high-grade PC could affect the phenotypic and functional features and thus the anti-tumor potential of NK cells. We show that while in the peritoneal fluid (PF) of low-grade PC most CD56dim NK cells show a relatively immature phenotype (NKG2A+KIR\u2013CD57\u2013CD16dim), in the PF of high-grade PC NK cells are, in large majority, mature (CD56dimKIR+CD57+CD16bright). Furthermore, in low-grade PC, PF-NK cells are characterized by a sharp down-regulation of some activating receptors, primarily NKp30 and DNAM-1, while, in high-grade PC, PF-NK cells display a higher expression of the PD-1 inhibitory checkpoint. The compromised phenotype observed in low-grade PC patients corresponds to a functional impairment. On the other hand, in the high-grade PC patients PF-NK cells show much more important defects that only partially reflect the compromised phenotype detected. These data suggest that the PC microenvironment may contribute to tumor escape from immune surveillance by inducing different NK cell impaired features leading to altered anti-tumor activity. Notably, after CRS/HIPEC treatment, the altered NK cell phenotype of a patient with a low-grade disease and favorable prognosis was reverted to a normal one. Our present data offer a clue for the development of new immunotherapeutic strategies capable of restoring the NK-mediated anti-tumor responses in association with the CRS/HIPEC treatment to increase the effectiveness of the current therapy

Metformin overdose causes platelet mitochondrial dysfunction in humans

Introduction. We have recently demonstrated that metformin intoxication causes mitochondrial dysfunction in several porcine tissues, including platelets. The aim of the present work was to clarify whether it also causes mitochondrial dysfunction (and secondary lactate overproduction) in human platelets, in-vitro and ex-vivo. Methods. Human platelets were incubated for 72 h with saline or increasing dose of metformin (in-vitro experiments). Lactate production, respiratory chain complex activities (spectrophotometry), mitochondrial membrane potential (flow-cytometry after staining with JC-1) and oxygen consumption (Clark-type electrode) were then measured. Platelets were also obtained from ten patients with lactic acidosis (arterial pH 6.97\ub10.18 and lactate 16\ub17 mmol/l) due to accidental metformin intoxication (serum drug level 32\ub114 mg/l) and ten healthy volunteers of similar sex and age. Respiratory chain complex activities were measured as above (ex-vivo experiments). Results. In-vitro, metformin dose-dependently increased lactate production (p<0.001), decreased respiratory chain complex I activity (p=0.009), mitochondrial membrane potential (p=0.003) and oxygen consumption (p<0.001) of human platelets. Ex-vivo, platelets taken from intoxicated patients had significantly lower complex I (p=0.045) and complex IV (p<0.001) activity compared to controls. Conclusions. Depending on dose, metformin can cause mitochondrial dysfunction and lactate overproduction in human platelets in-vitro and, possibly, in-vivo. Trial registration. NCT 0094212

Brettanomyces bruxellensis yeasts: impact on wine and winemaking

Yeasts belonging to the Brettanomyces/Dekkera genus are non-conventional yeasts, which affect winemaking by causing wine spoilage all over the world. This mini-review focuses on recent results concerning the presence of Brettanomyces bruxellensis throughout the wine processing chain. Here, culture-dependent and independent methods to detect this yeast on grapes and at the very early stage of wine production are encompassed. Chemical, physical and biological tools, devised for the prevention and control of such a detrimental species during winemaking are also presented. Finally, the mini-review identifies future research areas relevant to the improvement of wine safety and sensory profiles

Anales del III Congreso Internacional de Vivienda y Ciudad "Debate en torno a la nueva agenda urbana"

Acta de congresoEl III Congreso Internacional de Vivienda y Ciudad “Debates en torno a la NUEVa Agenda Urbana”, ha sido una apuesta de alto compromiso por acercar los debates centrales y urgentes que tensionan el pleno ejercicio del derecho a la ciudad. Para ello las instituciones organizadoras (INVIHAB –Instituto de Investigación de Vivienda y Hábitat y MGyDH-Maestría en Gestión y Desarrollo Habitacional-1), hemos convidado un espacio que se concretó con potencia en un debate transdisciplinario. Convocó a intelectuales de prestigio internacional, investigadores, académicos y gestores estatales, y en una metodología de innovación articuló las voces académicas con las de las organizaciones sociales y/o barriales en el Foro de las Organizaciones Sociales que tuvo su espacio propio para dar voz a quienes están trabajando en los desafíos para garantizar los derechos a la vivienda y los bienes urbanos en nuestras ciudades del Siglo XXI