Sorbed Anthracene Degradation by Sophorolipid Producing Yeasts

The organic pollutan adsorption/desorption process by microbial degradation had been less studied than metal ones. The sorption assays alone did not predict desorption, due to hysteresis, irreversibility, fixed compounds in different sites, with diverse desorption rates. Most of the studies dealt with bacteria rather than filamentous fungi and yeasts. So, our aims were to isolate yeasts from polluted sediments, to quantify its potential to uptake anthracene (An) and to evaluate the bioavailability by a desorption model. Yeasts were isolated from hydrocarbon-polluted samples, 40-isolates grew in anthracene-plates. Molecular characterization was achieved by sequence analysis of the ITS1-5.8S rRNA-ITS4 and 26S rRNA regions; morphological and physiological determination were also done. Candida parasilopsis, Pichia anomala and Rhodothorula mucilaginosa were the prevalent yeasts. An-degradation was assessed in soil-systems with 0, 50, 100, 150, 200 and 250 µg An/l, 3 differentes sorbens types, organic carbon, organic nitrogen, PAHs, sand:silt:clay, pH and cation exchange capacity. Sophorolipids excretion were confirmed by HPLC, UV-detector with active fraction at 9.669 min (RT 9.646 min = sophorolipid-standard). A desorption model with equilibrium, nonequilibrium and nondesorption areas, was applied to explain the experimental data, An-transformation was greater in the organic liquid-phase than in the soil-sorbed ones; the desorption-coefficients and soil components were negatively correlated with the kinetic parameters. The An-release depended on the sophorolipid excretion, soil matrix and particles sizes. Desorption parameters significantly fitted the yeast uptake, with R2 = 0.97, R2 = 0.90 and R2 = 0.97 for C. parasilopsis, P. anomala and R. mucilaginosa, respectively

Comparison of Faecal versus Rumen Inocula for the Estimation of NDF Digestibility

Cow faeces have been investigated as alternative inoculum to replace rumen fluid to determine neutral detergent fibre (NDF) digestibility (NDFD). Aims of this study were to estimate: (1) the NDFD (48 h) of feed ingredients using a rumen inoculum in comparison with faecal inocula from cows fed diets with different forage basis; (2) the undigestible NDF (uNDF) at 240 and 360 h with ruminal fluid and faecal inocula from lactating cows fed two different diets. At 48 h incubation, the NDFD was affected both by feed and type of inoculum (p < 0.01) and by their interaction (p = 0.03). Overall, the mean NDFD was higher for rumen inoculum than for faecal inocula (585 vs. 389 g/kg NDF, p < 0.05), and faecal inoculum obtained from cows fed hay-based diets gave lower NDFD than those from cows fed maize silage (367 vs. 440 g/kg, p < 0.05). At long incubation times, the average uNDF was affected by substrate, inoculum and incubation time (p < 0.01), but not by their interactions. For each inoculum, significantly lower values were obtained at 360 than at 240 h. Regressions between uNDF with rumen and with the tested faecal inocula resulted in r2 65 0.98. Despite the differences at 48 h, the uNDF showed that faecal inoculum could replace rumen fluid at longer incubation times

Model of Care for Adolescents and Young Adults with Cancer: The Youth Project in Milan

Adolescents and young adults (AYA) with cancer form a particular group of patients with unique characteristics, who inhabit a so-called "no man's land" between pediatric and adult services. In the last 10\u2009years, the scientific oncology community has started to pay attention to these patients, implementing dedicated programs. A standardized model of care directed toward patients in this age range has yet to be developed and neither the pediatric nor the adult oncologic systems perfectly fit these patients' needs. The Youth Project of the Istituto Nazionale Tumori in Milan, dedicated to AYA with pediatric-type solid tumors, can be seen as a model of care for AYA patients, with its heterogeneous multidisciplinary staff and close cooperation with adult medical oncologists and surgeons. Further progress in the care of AYA cancer patients is still needed to improve their outcomes

MTORC1-mediated inhibition of polycystin-1 expression drives renal cyst formation in tuberous sclerosis complex

Previous studies report a cross-talk between the polycystic kidney disease (PKD) and tuberous sclerosis complex (TSC) genes. mTOR signalling is upregulated in PKD and rapamycin slows cyst expansion, whereas renal inactivation of the Tsc genes causes cysts. Here we identify a new interplay between the PKD and TSC genes, with important implications for the pathophysiology of both diseases. Kidney-specific inactivation of either Pkd1 or Tsc1 using an identical Cre (KspCre) results in aggressive or very mild PKD, respectively. Unexpectedly, we find that mTORC1 negatively regulates the biogenesis of polycystin-1 (PC-1) and trafficking of the PC-1/2 complex to cilia. Genetic interaction studies reveal an important role for PC-1 downregulation by mTORC1 in the cystogenesis of Tsc1 mutants. Our data potentially explain the severe renal manifestations of the TSC/PKD contiguous gene syndrome and open new perspectives for the use of mTOR inhibitors in autosomal dominant PKD caused by hypomorphic or missense PKD1 mutations

Treatment at Relapse for Synovial Sarcoma of Children, Adolescents and Young Adults:From the State of Art to Future Clinical Perspectives

While the overall prognosis is generally quite satisfactory in children, adolescents and young adults with localised synovial sarcoma at first diagnosis, the outcome remains poor for patients after relapse. Conversely to the front-line standardised treatment options, patients with relapse generally have an individualised approach and to date, there is still a lack of consensus regarding standard treatment approaches. Studies on relapsed synovial sarcoma were able to identify some prognostic variables that influence post-relapse survival, in order to plan risk-adapted salvage protocols. Treatment proposals must consider previous first-line treatments, potential toxicities, and the possibility of achieving an adequate local treatment by new surgery and/or re-irradiation. Effective second-line drug therapies are urgently needed. Notably, experimental treatments such as adoptive engineered TCR-T cell immunotherapy seem promising in adults and are currently under validation also in paediatric patients.</p

The expression of mismatched repair genes and their correlation with clinicopathological parameters and response to neo-adjuvant chemotherapy in breast cancer

BACKGROUND: The DNA mismatch repair (MMR) pathway is an important post-replicative repair process. It is involved in the maintenance of genomic stability and MMR genes have therefore been named the proofreaders of replicating DNA. These genes repair the replicative errors of DNA and are thus imperative for genomic stability. The MMR genes have been found to be involved in promoting cytotoxicity, apoptosis, p53 phosphorylation and cell cycle arrest following exposure to exogenous DNA damaging agents. Loss of MMR function prevents the correction of replicative errors leading to instability of the genome, and can be detected by polymorphisms in micro satellites (1–6 nucleotide repeat sequences scattered in whole of the genome). This phenomenon, known as micro satellite instability (MSI), is a hallmark of MMR dysfunction and can be used as a marker of MMR dysfunction in colorectal and other malignancies. An alternative method for detection of MMR dysfunction is to test the expression of protein products of the MMR genes by immunohistochemistry (IHC), as mutations in these genes lead to reduced or absent expression of their gene products. Correlation between loss of MMR function and clinical, histopathological, behavioral parameters of the tumor and its response to chemotherapy in breast cancers may be of value in predicting tumor behavior and response to neoadjuvant chemotherapy (NACT). Neoadjuvant chemotherapy is an integral part of multimodal therapy for locally advanced breast cancer and predicting response may help in tailoring regimens in patients for optimum response. MATERIALS: After approval by the IRB(Institutional Review Board) and ethical committee of the hospital, 31 cases of locally advanced breast carcinoma (LABC) were studied to assess the correlation between MMR dysfunction, clinicopathological parameters and objective clinical response to neoadjuvant chemotherapy using immunohistochemistry. The immunohistochemical analysis for four MMR protein products -MLH1, MSH2, MSH6 and PMS2 was done in the pre NACT trucut biopsy specimen and after three cycles of NACT with C AF (cyclophosphamide, adriamycin, 5-fluorouracil) regimen, in the modified radical mastectomy specimen. RESULTS AND CONCLUSION: There was no significant correlation observed between expression of MMR proteins and age, family history, tumor size or histological type. However there was a statistically significant negative correlation between MLH1, MSH2 expression and histological grade. There was also a negative correlation observed between PMS2 expression after neo-adjuvant chemotherapy and clinical response. Cases with high post NACT expression of PMS2 were poor responders to chemotherapy. MSH6 was the most frequently altered MMR gene, with a negativity rate of 48% and the patients with high expression responded poorly to NACT. The study highlights the possible role of MMR expression in predicting aggressive tumor behavior (histological grade) and response to neoadjuvant chemotherapy in patients with LABC