β3-Adrenoreceptors as ROS Balancer in Hematopoietic Stem Cell Transplantation

In the last decades, the therapeutic potential of hematopoietic stem cell transplantation (HSCT) has acquired a primary role in the management of a broad spectrum of diseases including cancer, hematologic conditions, immune system dysregulations, and inborn errors of metabolism. The different types of HSCT, autologous and allogeneic, include risks of severe complications including acute and chronic graft-versus-host disease (GvHD) complications, hepatic veno-occlusive disease, lung injury, and infections. Despite being a dangerous procedure, it improved patient survival. Hence, its use was extended to treat autoimmune diseases, metabolic disorders, malignant infantile disorders, and hereditary skeletal dysplasia. HSCT is performed to restore or treat various congenital conditions in which immunologic functions are compromised, for instance, by chemo- and radiotherapy, and involves the administration of hematopoietic stem cells (HSCs) in patients with depleted or dysfunctional bone marrow (BM). Since HSCs biology is tightly regulated by oxidative stress (OS), the control of reactive oxygen species (ROS) levels is important to maintain their self-renewal capacity. In quiescent HSCs, low ROS levels are essential for stemness maintenance; however, physiological ROS levels promote HSC proliferation and differentiation. High ROS levels are mainly involved in short-term repopulation, whereas low ROS levels are associated with long-term repopulating ability. In this review, we aim summarize the current state of knowledge about the role of β3-adrenoreceptors (β3-ARs) in regulating HSCs redox homeostasis. β3-ARs play a major role in regulating stromal cell differentiation, and the antagonist SR59230A promotes differentiation of different progenitor cells in hematopoietic tumors, suggesting that β3-ARs agonism and antagonism could be exploited for clinical benefit.     

Multiplexed MRM-Based Proteomics Identified Multiple Biomarkers of Disease Severity in Human Heart Failure

Heart failure (HF) is a complex disease due to the intricate interplay of several mechanisms, which therefore implies the need for a multimarker strategy to better personalize the care of patients with HF. In this study, we developed a targeted mass spectrometry approach based on multiple reaction monitoring (MRM) to measure multiple circulating protein biomarkers, involved in cardiovascular disease, to address their relevance in the human HF, intending to assess the feasibility of the workflow in the disease monitoring and risk stratification. In this study, we analyzed a total of 60 plasma proteins in 30 plasma samples from eight control subjects and 22 age- and gender- matched HF patients. We identified a panel of four plasma proteins, namely Neuropilin-2, Beta 2 microglobulin, alpha-1-antichymotrypsin, and complement component C9, that were more abundant in HF patients in relation to disease severity and pulmonary dysfunction. Moreover, we showed the ability of the combination of these candidate proteins to discriminate, with sufficient accuracy, HF patients from healthy subjects. In conclusion, we demonstrated the feasibility and potential of a proteomic workflow based on MRM mass spectrometry for the evaluation of multiple proteins in human plasma and the identification of a panel of biomarkers of HF severity.     

A forgotten centre of ceramic production in Southern Levant: Preliminary analytical study of the Early Bronze Age pottery from Tell el-Far‘ah North (West Bank)

The paper presents an archaeometric investigation of ancient ceramics from the archaeological site of Tell el-Far‘ah North (West Bank), dated to the south-Levantine Early Bronze I-II (EB I-II, 3300–2700 BC). The application of mineralogical and chemical analyses by optical and scanning electron microscopy yielded the identification of petro-fabrics that allow the reconstruction of the raw material nature used in the manufacture as well as its provenance. The results indicate that the ceramics were produced using calcareous clays with inclusions of sedimentary rock fragments, calcite crystals, iron oxides and quartz. Two basic fabrics have been identified according to the presence or absence of coarse and angular calcite crystals. The optical activity of the matrix and the presence of calcareous inclusions indicate a maximum firing temperature lower than 850?°C and in the range 700–850?°C for those ceramics showing an initial decarbonation process of calcareous inclusions. The nature of the inclusions supports a local supply of raw materials. Moreover, the comparison between the ceramic material of the two subsequent occupational phases at the site allowed achieving important information about the development of the material and technological knowledge reached by its ancient potters, in the transition from the EB I community to the EB II urban centre.     

Survival in vitro and virulence of Trypanosoma cruzi in açaí pulp in experimental acute Chagas disease

Chagas disease is a parasitic infection with high socioeconomic impact throughout Latin America. Although this severe, incurable disease can be transmitted by several routes, oral transmission is currently the most important route in the Amazon Basin. A?aí pulp has nutritional properties and is popular throughout Brazil and abroad. However, this pulp has been associated with microepidemics of acute Chagas disease (ACD) in northern Brazil, where a?aí fruit is the main food supplement. In this study, we examined the in vitro survival and in vivo virulence of Trypanosoma cruzi Y strain in a?aí pulp. Aliquots of in natura a?aí pulp produced in Belém city in the northern Brazilian state of Pará were mixed with 10? trypomastigotes. The samples were incubated at room temperature or at 4 or -20°C for various periods, and the parasites were isolated by forced sieving. The resulting eluates were examined by microscopy, and the trypomastigotes were administered intraperitoneally, orally, or by gavage to immunodeficient mice (C.B-17-Prkdc(scid)/PasUnib) that had been pretreated with antibiotics. Parasitemia was quantified by the Brener method, and mortality was recorded daily. All routes of administration resulted in ACD. A 5-day delay in the onset of parasitemia occurred with oral administration. The survival and virulence of the parasites were unaffected by prior incubation at room temperature for 24 h, at 4°C for 144 h, and at -20°C for 26 h. These results indicate that T. cruzi can survive and retain its virulence in a?aí pulp under various conditions and that cooling and freezing are not suitable methods for preventing foodborne ACD.     

Mevalonate Pathway Blockade,Mitochondrial Dysfunction and Autophagy: A Possible Link

The mevalonate pathway, crucial for cholesterol synthesis, plays a key role in multiple cellular processes. Deregulation of this pathway is also correlated with diminished protein prenylation, an important post-translational modification necessary to localize certain proteins, such as small GTPases, to membranes. Mevalonate pathway blockade has been linked to mitochondrial dysfunction: especially involving lower mitochondrial membrane potential and increased release of pro-apoptotic factors in cytosol. Furthermore a severe reduction of protein prenylation has also been associated with defective autophagy, possibly causing inflammasome activation and subsequent cell death. So, it is tempting to hypothesize a mechanism in which defective autophagy fails to remove damaged mitochondria, resulting in increased cell death. This mechanism could play a significant role in Mevalonate Kinase Deficiency, an autoinflammatory disease characterized by a defect in Mevalonate Kinase, a key enzyme of the mevalonate pathway. Patients carrying mutations in the MVK gene, encoding this enzyme, show increased inflammation and lower protein prenylation levels. This review aims at analysing the correlation between mevalonate pathway defects, mitochondrial dysfunction and defective autophagy, as well as inflammation, using Mevalonate Kinase Deficiency as a model to clarify the current pathogenetic hypothesis as the basis of the disease.     

Temperature modulates the production and activity of a metalloprotease from Pseudomonas fluorescens 07A in milk

This work evaluated the expression and activity of a metalloprotease released by Pseudomonas fluorescens 07A in milk. Low relative expression of the protease by the strain was observed after incubation for 12 h at 25°C while the strain was in the logarithmic growth phase. After 24 h, protease production significantly increased and remained constant for up to 48 h, a time range during which the strain remained in the stationary phase. Conversely, at refrigeration temperatures, at 12 h the strain was still in the lag phase and expressed the protease at higher levels than when the logarithmic phase was reached. Casein fractions were highly degraded by P. fluorescens 07A, the purified protease, and the bacterial pellet on d 7 of incubation at 25°C and to a lesser extent at 10°C for the sample incubated with the bacterium. Heat treatment at 90°C for 5 min completely inactivated the proteolytic activity of the purified protease and the bacterial pellet. This work contributes to the knowledge about the conditions of milk storage that influence the production and activity of this extracellular metalloprotease. The results demonstrate the need to find alternative strategies to control the synthesis and activity of proteolytic enzymes in the dairy industry to ensure the quality of processed products.     

Psychological Safety,Knowledge Sharing,and Creative Performance in Healthcare Teams

We examined how psychological safety fosters knowledge‐sharing processes and enables team creative performance. Using a multi‐respondent design, we tested our hypotheses using survey data collected from 73 patient‐centred healthcare teams working in the field on rare diseases. The data were analysed using latent class regression analysis. We confirmed that a high level of psychological safety within the team is a significant predictor of creative team performance and is mediated by the sharing of two types of knowledge: information and know‐how.