TP63 and TP73 in cancer, an unresolved “family” puzzle of complexity, redundancy and hierarchy

AbstractTP53 belongs to a small gene family that includes, in mammals, two additional paralogs, TP63 and TP73. The p63 and p73 proteins are structurally and functionally similar to p53 and their activity as transcription factors is regulated by a wide repertoire of shared and unique post-translational modifications and interactions with regulatory cofactors. p63 and p73 have important functions in embryonic development and differentiation but are also involved in tumor suppression. The biology of p63 and p73 is complex since both TP63 and TP73 genes are transcribed into a variety of different isoforms that give rise to proteins with antagonistic properties, the TA-isoforms that act as tumor-suppressors and DN-isoforms that behave as proto-oncogenes. The p53 family as a whole behaves as a signaling “network” that integrates developmental, metabolic and stress signals to control cell metabolism, differentiation, longevity, proliferation and death. Despite the progress of our knowledge, the unresolved puzzle of complexity, redundancy and hierarchy in the p53 family continues to represent a formidable challenge

A case of allergic enterocolitis to milk protein in a down baby

Anna, a term baby born by Caesarean section, firstborn, Apgar 8/9, born SGA 2.630 g weight; performed in karyotype of Down syndrome suspected ’free trisomy of chromosome 21’, echocardiography and abdominal ultrasound normal, ABR REFER, discharged in 8th day of life with diet of mother’s milk integrated with zero infant formula. Hospitalisation at one month of life due to serious clinical conditions (dehydration, hypovolemic shock, metabolic acidosis, PCR 67,4 mg/L, PCT 4,45 ng/ml, leukocytosis 63870/microL, weight 2447 g); negative blood, liquor, urine and stool cultures; Chest and Abdomen X-ray showed meteoric distension of the intestinal loops. She began antibiotic (Ampicillin+Sulbactam, Netilmicin, Ceftazidime) and immunoglobulin therapy with improvement and reduction of inflammatory markers; feeding with zero infant formula. After the fourth day of hospitalisation spontaneous emission of greenish bloody stools and then liquid stools, hypotonus, metabolic acidosis, bulbous abdomen, fever, increased inflammatory markers and leukocytosis occurred despite antibiotic therapy. New negatives cultures tested, negative parasitological faecal examination, positive faecal calprotectin (702.59 mg/kg); lymphocyte subpopulations and normal immunoglobulins. Anaemia with need of blood transfusion. Therapy replaced with Meropenem and Vancomycin and diet with hydrolyzed infant formula with slight improvements. The appearance of two similar to previous episodes in the following days suggested to treat with antibiotics and immunoglobulins. After gastroenterological consulting, in allergic enterocolitis to milk protein suspect, it replaced diet with hydrolyzed infant formula with amino acids. The following days progressive clinical improvement noted, weight increase, normal inflammatory markers, good conditions and subsequently discharge. Three weeks later, during medical check-up, she appeared in good clinical condition, increase in weight of 650

Drivers of increased soil respiration in a poplar coppice exposed to elevated CO2

Background and Aims. The response of soil respiration (SR) to elevated CO2 is driven by a number of processes and feedbacks. This work aims to i) detect the effect of elevated CO2 on soil respiration during the second rotation of a short rotation forest, at two levels of N availability; and ii) identify the main drivers behind any changes in soil respiration. Methods. A poplar plantation (POP-EUROFACE) was grown for two rotations of three years under elevated CO2 maintained by a FACE (Free Air CO2 Enrichment) technique. Root biomass, litter production and soil respiration were followed for two consecutive years after coppice. Results. In the plantation, the stimulation of fine root and litter production under elevated CO2 observed at the beginning of the rotation declined over time. Soil respiration (SR) was continuously stimulated by elevated CO2, with a much larger enhancement during the growing (up to 111 %) than in the dormant season (40 %). The SR increase at first appeared to be due to the increase in fine root biomass, but at the end of the 2nd rotation was supported by litter decomposition and the availability of labile C. Soil respiration increase under elevated CO2 was not affected by N availability. Conclusions. The stimulation of SR by elevated CO2 was sustained by the decomposition of above and belowground litter and by the greater availability of easily decomposable substrates into the soil. C losses through SR were greater in the last year of the plantation due to a lack of effect of elevated CO2 on C allocation to roots, reducing the potential for C accumulation

Also adipose tissue pays consequencies of perinatal asphyxia

D.R. is born at term of physiological pregnancy by caesarean section. Birth weight was 3520 g, APGAR 7/9. At birth he presented axial hypotonia, hyporeactivity, groan, mild respiratory distress. Started Non Invasive Ventilation for 2 days with good improvement of outcome. At 4 day life, we started antimicrobial therapy and immunoglobulins ev because of elevated inflammatory markers and low platelet counts (PLT 47000/mcl) confirmed at the blood smear. After 2 weeks, on the neck and on the right cheek, finding of erythematous nodules of a few millimetres of diameter. In the days after, the lesions are also extended to the left cheek and became larger up to about 3 cm. At the ultrasound they appeared as ‘delimited echogenic areas of 19 × 14 mm at left, 17 × 12 mm at right whit intrinsic vascularisation and of irregular structure. Laboratory pannels (hepatic, renal, coltural exams, procalcitonin) were negative, ESR 24 mm/h, CRP 23.6 mg/L. About 30 days after, we see a reduction of the lesions in spite of a persistent increase of inflammatory markers. Therefore, a bacterial aetiology appeared ulikely saw that antimicrobial therapy so soon established, had no effects on them. Subcutaneous fat necrosis of the newborn is a relatively rare and transient condition that appeared in the first weeks of life in term infants with a perinatal suffering. This condition is caractherized by single or multiple subcutaneous nodules, isolated or confluent in plaques, erythematous/purplish, sometimes with little depressions, calcifications or necrosis inside; symmetrically distributed on the back, shoulders, buttocks, cheeks and at the root of the limbs; often painful at palpation. These nodules grow for some weeks and completely resolve within few months. Etiopathogenesis is probably linked to ischaemic injury, hypoxia, hypothermia and/or stress damage on the immature adipose tissue in infants with perinatal asphyxia. Maternal hypertension, gestational diabetes, family history of thrombophilia and dyslipidemia are considered risk factors. The diagnosis is clinical; the cutaneous biopsy is of support. Important for diagnosis are also the Ultrasonography and RMN. Hypercalcemia is the most dangerous complication; less frequent consequencies are thrombocytopenia, metabolic disorders (hypertriglyceridemia, hypoglycemia) and atrophic development of the nodular lesions

Development of a Steam Generator Mock-Up for EU DEMO Fusion Reactor: Conceptual Design and Code Assessment

Recent R&D activities in nuclear fusion have identified the DEMO reactor as the ITER successor, aiming at demonstrating the technical feasibility of fusion plants, along with their commercial exploitation. However, the pulsed operation of the machine causes an “unconventional” operation of the system, posing unique challenges to the functional feasibility of the steam generator, for which it is necessary to define and qualify a reference configuration for DEMO. In order to facilitate the transitions between different operational regimes, the Once Through Steam Generator (OTSG) is considered to be a suitable choice for the DEMO primary heat transfer systems, being characterized by lower thermal inertia with respect to the most common U-tube steam generators. In this framework, the ENEA has undertaken construction of the STEAM facility at Brasimone R.C., aiming at characterizing the behavior of the DEMO OTSG and related water coolant systems in steady-state and transient conditions. A dedicated OTSG mock-up has been conceived and designed, adopting a scaling procedure, keeping the height 1:1 of the DEMO OTSGs. The conceptual design has been supported by RELAP5/Mod3.3 thermal-hydraulic calculations. CFD and FEM codes have been used for fluid-dynamic analyses and mechanical stress analyses, respectively, in specific parts of the component

Long-term treatment with adalimumab in psoriatic arthritis: serum adalimumab concentration, immunogenicity and the link with clinical response

Objectives: An observational study to evaluate the relationship between serum concentrations of adalimumab and disease activity in patients receiving long-term adalimumab treatment for psoriatic arthritis. Methods: Serum adalimumab and adalimumab antidrug antibodies were quantified by enzyme linked immunosorbent assay. Disease activity was assessed using Disease Activity Score (44 joint measures). Serum C-reactive protein was quantified using standard methods. Results: A total of 30 patients were recruited. There were significant inverse correlations between serum adalimumab concentration and serum C-reactive protein (CRP) concentration [r = −0.43], the number of tender joints (r = −0.4), and Disease Activity Score (DAS44)-CRP (r = −0.36). Mean serum adalimumab levels were significantly higher in patients with DAS44-CRP <1.6 than in patients with DAS44-CRP ≥1.6. Conclusions: Serum adalimumab could be an important tool that may improve the management of psoriatic arthritis in patients responding to long-term treatment

Soil organic C variability and microbial functions in a Mediterranean agro-forest ecosystem

Five soils characterised by different agro-forest managements, typical of Mediterranean environment and with increasing human impact were chosen in Sardinia (Italy): two vineyards with different management systems, a rotation hay crop-pasture and a forest (Quercus suber L.). The study aimed to investigate the relationships between C storage and microbial functionality in soil under different managements. Pools of total organic C and microbial biomass C were determined, as well as the loss of organic C due to microbial respiration (basal and cumulative) and several microbial indices (metabolic, mineralization, and microbial quotient) as indicators of the microbial efficiency in the use of energy and the degree of substrate limitation for soil microbes. Enzymes were chosen on their relevance in the C (β-cellobiohydrolase, N-acetyl-β-glucosaminidase, β-glucosidase, α-glucosidase), N (leucine aminopeptidase), S (arylsulphatase) and P (acid phosphatase) cycling and were used as indicators of functional diversity in soil. Organic C pools and enzyme activities on average increased noticeably in soils with a lower human impact showing the highest values in forest and the lowest in the vineyards, following the trend of organic matter availability. The trend in functional diversity reflected the increase of microbial pool and organic C availability: the vineyards showed a lower Shannon’s diversity index, whilst pasture and forest sites reached the maximum levels of functional diversity. These soils showed an increase of microbial efficiency in the use of available resources and the decrease of substrate limitation for soil microbes

STEAM Experimental Facility: A Step Forward for the Development of the EU DEMO BoP Water Coolant Technology

Within the EUROfusion roadmap for the technological development of the European-DEMOnstration (EU-DEMO) reactor, a key point has been identified in the discontinuous operation (pulse-dwell-pulse) of the machine. Water Cooled Lithium Lead (WCLL) Breeding Blanket (BB) Primary Heat Transfer Systems (PHTSs) adopt technology and components commonly used in nuclear fission power plants, whose performances could be negatively affected by the above mentioned pulsation, as well as by low-load operation in the dwell phase. This makes mandatory a full assessment of the functional feasibility of such components through accurate design and validation. For this purpose, ENEA Experimental Engineering Division at Brasimone R.C. aims at realizing STEAM, a water operated facility forming part of the multipurpose experimental infrastructure Water cooled lithium lead -thermal-HYDRAulic (W-HYDRA), conceived to investigate the water technologies applied to the DEMO BB and Balance of Plant systems and components. The experimental validation has the two main objectives of reproducing the DEMO operational phases by means of steady-state and transient tests, as well as performing dedicated tests on the steam generator aiming at demonstrating its ability to perform as intended during the power phases of the machine. STEAM is mainly composed of primary and secondary water systems reproducing the thermodynamic conditions of the DEMO WCLL BB PHTS and power conversion system, respectively. The significance of the STEAM facility resides in its capacity to amass experimental data relevant for the advancement of fusion-related technologies. This capability is attributable to the comprehensive array of instruments with which the facility will be equipped and whose strategic location is described in this work. The operational phases of the STEAM facility at different power levels are presented, according to the requirements of the experiments. Furthermore, a preliminary analysis for the definition of the control strategy for the OTSG mock-up was performed. In particular, two different control strategies were identified and tested, both keeping the primary mass flow constant and regulating the feedwater mass flow to follow a temperature set-point in the primary loop. The obtained numerical results yielded preliminary feedback on the regulation capability of the DEMO steam generator mock-up during pulsed operation, showing that no relevant overtemperature jeopardized the facility integrity, thanks to the high system responsivity to rapid load variations