Insights into Thymus Development and Viral Thymic Infections

T-cell development in the thymus is a complex and highly regulated process, involving a wide variety of cells and molecules which orchestrate thymocyte maturation into either CD4+ or CD8+ single-positive (SP) T cells. Here, we briefly review the process regulating T-cell differentiation, which includes the latest advances in this field. In particular, we highlight how, starting from a pool of hematopoietic stem cells in the bone marrow, the sequential action of transcriptional factors and cytokines dictates the proliferation, restriction of lineage potential, T-cell antigen receptors (TCR) gene rearrangements, and selection events on the T-cell progenitors, ultimately leading to the generation of mature T cells. Moreover, this review discusses paradigmatic examples of viral infections affecting the thymus that, by inducing functional changes within this lymphoid gland, consequently influence the behavior of peripheral mature T-lymphocytes

The expression of inhibitor of bruton's tyrosine kinase gene is progressively up regulated in the clinical course of chronic lymphocytic leukaemia conferring resistance to apoptosis.

Chronic lymphocytic leukaemia (CLL) is the most common B-cell malignancy with a variable clinical outcome. Biomarkers of CLL progression are required for optimising prognosis and therapy. The Inhibitor of Bruton's tyrosine kinase-isoform α (IBTKα) gene encodes a substrate receptor of Cullin 3-dependent E3 ubiquitin ligase, and promotes cell survival in response to the reticulum stress. Searching for novel markers of CLL progression, we analysed the expression of IBTKα in the peripheral blood B-cells of CLL patients, before and after first line therapy causing remission. The expression of IBTKα was significantly increased in disease progression, and decreased in remission after chemotherapy. Consistently with a pro-survival action, RNA interference of IBTKα increased the spontaneous and Fludarabine-induced apoptosis of MEC-1 CLL cells, and impaired the cell cycle of DeFew B-lymphoma cells by promoting the arrest in G0/G1 phase and apoptosis. Consistently, RNA interference of IBTKα up regulated the expression of pro-apoptotic genes, including TNF, CRADD, CASP7, BNIP3 and BIRC3. Our results indicate that IBTKα is a novel marker of CLL progression promoting cell growth and resistance to apoptosis. In this view, IBTKα may represent an attractive cancer drug target for counteracting the therapy-resistance of tumour cells

Documentazione e interventi delle Regioni in relazione alle misure adottate per il contenimento dell’emergenza Covid-19 e relativa giurisprudenza amministrativa.

Osservatorio emergenza Covid-19: Rassegna di documentazione e interventi delle Regioni in relazione alle misure adottate per il contenimento dell’emergenza Covid-19 (decreti, ordinanze e provvedimenti amministrativi) e relativa giurisprudenza amministrativa (T.A.R. e Consiglio di Stato) sulla legittimità delle misure di contenimento dell'emergenza

Microtubule-dependent Organization of Vaccinia Virus Core-derivd Early mRNAs into Distinct Cytoplasmic Structures.

Vaccinia virus (vv) early transcription can be reconstituted in vitro from purified virions; in this assay mRNAs are made inside the viral core and subsequently extruded. Although the in vitro process has been extensively characterized, relatively little is known about vv early transcription in vivo. In the present study the fate of vv early mRNAs in infected HeLa cells was followed by BrUTP transfection and confocal and electron microscopy. The extruded vv early mRNAs were found to be organized into unique granular cytoplasmic structures that reached a size up to 1 μm. By EM these structures appeared as amorphous electron-dense cytoplasmic aggregates that were surrounded by ribosomes. Confocal images showed that the RNA structures were located some distance away from intracellular cores and that both structures appeared to be aligned on microtubules (MTs), implying that MT tracks connected mRNAs and cores. Accordingly, intact MTs were found to be required for the typical punctate organization of viral mRNAs. Biochemical evidence supported the notion that vv mRNAs were MT associated and that MT depletion severely affected viral (but not cellular) mRNA synthesis and stability. By confocal microscopy the viral mRNA structures appeared to be surrounded by molecules of the translation machinery, showing that they were active in protein synthesis. Finally, our data suggest a role for a MT and RNA-binding viral protein of 25 kDa (gene L4R), in mRNA targeting away from intracellular cores to their sites of cytoplasmic accumulation

GDM-complicated pregnancies: focus on adipokines

Gestational diabetes mellitus (GDM) is a serious complication of pregnancy and is defined as a state of glucose intolerance that is first diagnosed and arises during gestation. Although the pathophysiology of GDM has not yet been thoroughly clarified, insulin resistance and pancreatic β-cell dysfunction are considered critical components of its etiopathogenesis. To sustain fetus growth and guarantee mother health, many significant changes in maternal metabolism are required in normal and high-risk pregnancy accompanied by potential complications. Adipokines, adipose tissue-derived hormones, are proteins with pleiotropic functions including a strong metabolic influence in physiological conditions and during pregnancy too. A growing number of studies suggest that various adipokines including adiponectin, leptin, visfatin, resistin and tumor necrosis factor α (TNF-α) are dysregulated in GDM and might have pathological significance and a prognostic value in this pregnancy disorder. In this review, we will focus on the current knowledge on the role that the aforementioned adipokines play in the development and progression of GDM.Gestational diabetes mellitus (GDM) is a serious complication of pregnancy and is defined as a state of glucose intolerance that is first diagnosed and arises during gestation. Although the pathophysiology of GDM has not yet been thoroughly clarified, insulin resistance and pancreatic β-cell dysfunction are considered critical components of its etiopathogenesis. To sustain fetus growth and guarantee mother health, many significant changes in maternal metabolism are required in normal and high-risk pregnancy accompanied by potential complications. Adipokines, adipose tissue-derived hormones, are proteins with pleiotropic functions including a strong metabolic influence in physiological conditions and during pregnancy too. A growing number of studies suggest that various adipokines including adiponectin, leptin, visfatin, resistin and tumor necrosis factor α (TNF-α) are dysregulated in GDM and might have pathological significance and a prognostic value in this pregnancy disorder. In this review, we will focus on the current knowledge on the role that the aforementioned adipokines play in the development and progression of GDM

Steel-based applications in earthquake-prone areas

Steel-Earth project aims at distributing among technicians, engineers, design companies and standardization bodies the results of three past RFCS projects (Steel-Retro [3], Opus [2] and PrecaSteel [1]), providing useful tools for the design and for the retrofit of existing buildings. Technical documents and practical applications to case studies, regarding design of steel and composite steel/concrete buildings and innovative steel-based techniques for the retrofit of existing r.c. and masonry constructions, have been elaborated and collected into a volume distributed during the final workshop of the dissemination project. Pre-normative and background documents concerning the design of steel and composite structures and the rehabilitation of existing constructions have been prepared. A lot of attention has been paid to the analysis of the influence of overstrength factors on the seismic design of steel and composite structures. The prepared documents have been distributed to the attending people and to the members of WG 2 (CEN/TC 250/SC 8/WG 2 “Steel and Composite Structures”) during the final workshop of the project. Technical sheets, working examples and background documents have been translated into several languages (German, French, Italian, Romanian and Greek) and are free available on the website of the project (https://www.steelconstruct.com/site/), where information regarding Steel-Earth are also presented.11 Workshops in Italy, Greece, Germany, Belgium, Portugal, Spain and Romania and 5 conferences in Emilia-Romagna have been organized, as well as 2 practical courses for engineers and academic people in Pavia (Italy). Flash-drives with the technical documents and applications elaborated in Steel-Earth have been distributed to the attending people

Facing covid-19 pandemic in a tertiary hospital in Milan: Prevalence of burnout in nursing staff working in sub-intensive care units

In early March 2020, Italy became the epicenter of the Coronavirus Disease 2019 (COVID-19) pandemic in Europe. A different organization of hospital units was required to take care of patients affected by acute respiratory failure caused by COVID-19. This study aimed to evaluate the prevalence of burnout in two sub-intensive care units (SICUs) of the COVID-19 hub center of the Lombardia region in Milan (Italy). All nurses and healthcare assistants working in the SICUs during June 2020 were included in the study. Burnout was assessed via the Maslach Burnout Inventory questionnaire. One hundred and five (84%) SICU staff participated in the study. The prevalence of high burnout for nurses and healthcare assistants was 61.9% for emotional exhaustion, 47.6% for depersonalization and 34.3% for personal accomplishment. Depersonalization was significantly more frequent in younger nurses (p = 0.009). Nurses were 4.5 times more likely to have burnout than healthcare assistants. Burnout was a common condition among healthcare workers operating in SICUs during the pandemic. Urgent actions are needed, especially for nurses, as well as preventive strategies for future pandemic scenarios

Safety of B. abortus rough mutant strain RB51 administration in Buffalo cows

The objective of this study was to determine if B. abortus rough mutant strain RB51 is eliminated in Buffalo milk. Five milk buffaloes were inoculated with the triple of the recommended calfhood dose (3.0 – 10.2 x 1010 cfu/ml) of B. abortus RB51 strain by subcutaneous route in the right axillary region. Milk samples were taken aseptically on a daily basis for the first 30 days and weekly for the second and third months. The samples were inoculated on Brucella Medium Base (BMB) (Oxoid) and Rifampin Brucellae Medium (RBM) and incubated under 10% CO2 at 37°C for 10 days. The suspicious colonies were recultured in BMB and RBM. PCR analysis was also performed on milk samples. There were no isolations of bacteria with characteristics of Brucella from any of the milk samples collected during 90 days of the study. However Brucella RB51 DNA was detected on day 2 and 3 post vaccination in one buffalo cow and on day 21 post vaccination in another buffalo cow. It was concluded that the strain used at this dose wasn't eliminated by milk in Buffaloes inoculated during lactation, however PCR positive results underline the necessity of milk pasteurization in order to minimize food-chain exposure

Effect of mannan oligosaccharides on rabbit performance, digestibility and rectal Bacterial anaerobic populations during an episode of epizootic rabbit enteropathy

[EN] The effect of three levels of mannan oligosaccharides (MOS at 0.5, 1.0 and 1.5 g/kg diet) compared to dietary antibiotic supplementation (ANT, colistin sulphate 144, tylosin 100 and oxytetracycline 1000 ppm) and to a diet without MOS or medication (control group) were studied on 5 groups of rabbits (n=342 cages/group and 2 rabbits/cage) from weaning (35 d) to 60 d of age in a farm with an anamnestic history of Epizootic Rabbit Enteropathy (ERE). Mortality rate was recorded daily. Thirty two cages per group were randomly chosen to record growth performance and rectal anaerobic microbial population. Live weight and feed intake were recorded weekly. At 49 d of age rectal swabs were collected with cotton swabs from 8 rabbits per group and the anaerobic microbial population was counted. Feed digestibility was determined per cage using acid insoluble ash as an internal marker, collecting faeces from 57 to 59 d of age. An episode of ERE occurred during the second and the third week of the trial. The control group showed a high mortality rate during the fattening period (78%) and was not considered for further measurements. Total mortality rate was higher (P<0.05) for rabbits fed antibiotics (34.2%) than for those fed MOS (17.7, 7.75 and 17.1 %, for MOS at 0.5, 1.0 and 1.5 g/kg diet, respectively), with the lowest mortality rate being for those with a 1.0 g MOS/kg diet. Medicated rabbits showed similar growth rates compared to the average of those fed MOS diets (38.6 g/d on average), but impaired feed conversion ratio (FCR) and nutrient digestibility (P<0.003). Rabbits fed MOS at 1.0 g/kg showed better growth rates, FCR and nutrient digestibility (P<0.01) than those fed 1.5 g/kg MOS. Total anaerobic and Clostridium spp. counts were higher in medicated animals compared to those fed MOS, with those fed 1 g/kg MOS showing the lowest value (P<0.001). Under critical conditions due to an episode of ERE, a concentration of 1.0 g/kg MOS in the diet, could reduce rabbit mortality and improve growth performance.Bovera, F.; Nizza, A.; Marono, S.; Mallardo, K.; Piccolo, G.; Tudisco, R.; De Martino, L.... (2010). Effect of mannan oligosaccharides on rabbit performance, digestibility and rectal Bacterial anaerobic populations during an episode of epizootic rabbit enteropathy. World Rabbit Science. 18(1):9-16. doi:10.4995/wrs.2010.18.0291618

Cannabidiolic acid in Hemp Seed Oil Table Spoon and Beyond

Cannabidiolic acid (CBDA) is the main precannabinoid in industrial hemp. It represents a common constituent of hemp seed oil, but mainly abundant in the aerial parts of the plant (including their processing waste). Thus, the optimization of fast and low-cost purification strategies is mandatory, as well as a deep investigation on its nutraceutical and cosmeceutical properties. To this purpose, CBDA content in hemp seed oil is evaluated, and its recovery from wasted leaves is favorably achieved. The cytotoxicity screening towards HaCaT cells, by means of MTT, SRB and LDH release assays, suggested it was not able to decrease cell viability or perturb cell integrity up to 10 μM concentration. Thus, the ability of CBDA to differentially modulate the release of proinflammatory cytokines and chemokines mediators has been evaluated, finding that CBDA decreased IFN-γ, CXCL8, CXCL10, CCL2, CCL4 and CCL5, mostly in a dose-dependent manner, with 10 μM tested concentration exerting the highest activity. These data, together with those from assessing antimicrobial activity against Gram(+) and Gram(-) bacteria and the antibiofilm formation, suggest that CBDA is able to counteract the inflammatory response, also preventing bacteria colonization