Fat-specific FUS-DDIT3-transgenic mice establish PPARgamma inactivation is required to liposarcoma development.

Peer reviewe

Impact of growth temperature on exopolysaccharide production and probiotic properties of Lactobacillus paracasei strains isolated from kefir grains

EPS-producing LAB are widely used in the dairy industry since these polymers improve the viscosity and texture of the products. Besides, EPS might be responsible for several health benefits attributed to probiotic strains. However, growth conditions (culture media, temperature, pH) could modify EPS production affecting both technological and probiotic properties. In this work, the influence of growth temperature on EPS production was evaluated, as well as the consequences of these changes in the probiotic properties of the strains. All Lactobacillus paracasei strains used in the study showed changes in EPS production caused by growth temperature, evidenced by the appearance of a high molecular weight fraction and an increment in the total amount of produced EPS at lower temperature. Nevertheless, these changes do not affect the probiotic properties of the strains; L. paracasei strains grown at 20 °C, 30 °C and 37 °C were able to survive in simulated gastrointestinal conditions, to adhere to Caco-2 cells after that treatment and to modulate the epithelial innate immune response. The results suggest that selected L. paracasei strains are new probiotic candidates that can be used in a wide range of functional foods in which temperature could be used as a tool to improve the technological properties of the product.Centro de Investigación y Desarrollo en Criotecnología de Alimento

Lactic Acid Bacteria Isolated from Fermented Doughs in Spain Produce Dextrans and Riboflavin

Many lactic acid bacteria (LAB) produce metabolites with applications in the food industry, such as dextran-type exopolysaccharides (EPS) and riboflavin (vitamin B2). Here, 72 bacteria were isolated from sourdoughs made by Spanish bread-makers. In the presence of sucrose, colonies of 22 isolates showed a ropy phenotype, and NMR analysis of their EPS supported that 21 of them were dextran producers. These isolates were identified by their random amplified polymorphic DNA (RAPD) patterns and their rrs and pheS gene sequences as LAB belonging to four species (Weissella cibaria, Leuconostoc citreum, Leuconostoc falkenbergense and Leuconostoc mesenteroides). Six selected strains from the Leuconostoc (3) and Weissella (3) genera grew in the absence of riboflavin and synthesized vitamin B2. The EPS produced by these strains were characterized as dextrans by physicochemical analysis, and the L. citreum polymer showed an unusually high degree of branching. Quantification of the riboflavin and the EPS productions showed that the W. cibaria strains produce the highest levels (585–685 μg/and 6.5–7.4 g/L, respectively). Therefore, these new LAB strains would be good candidates for the development of fermented foods bio-fortified with both dextrans and riboflavin. Moreover, this is the first report of riboflavin and dextran production by L. falkenbergense.This research was funded by the Spanish Ministry of Science, Innovation and Universities, (grants RTI2018-097114-B-I00 and PCIN-2017-075), by the Basque Government Industry and Education Department (grant PIBA_2020_1_0032) and by the University of the Basque Country (General Grant to Research Groups (GIU 19/014))

Lactic Acid Bacteria Isolated from Fermented Doughs in Spain Produce Dextrans and Riboflavin

Many lactic acid bacteria (LAB) produce metabolites with applications in the food industry, such as dextran-type exopolysaccharides (EPS) and riboflavin (vitamin B2). Here, 72 bacteria were isolated from sourdoughs made by Spanish bread-makers. In the presence of sucrose, colonies of 22 isolates showed a ropy phenotype, and NMR analysis of their EPS supported that 21 of them were dextran producers. These isolates were identified by their random amplified polymorphic DNA (RAPD) patterns and their rrs and pheS gene sequences as LAB belonging to four species (Weissella cibaria, Leuconostoc citreum, Leuconostoc falkenbergense and Leuconostoc mesenteroides). Six selected strains from the Leuconostoc (3) and Weissella (3) genera grew in the absence of riboflavin and synthesized vitamin B2. The EPS produced by these strains were characterized as dextrans by physicochemical analysis, and the L. citreum polymer showed an unusually high degree of branching. Quantification of the riboflavin and the EPS productions showed that the W. cibaria strains produce the highest levels (585–685 μg/and 6.5–7.4 g/L, respectively). Therefore, these new LAB strains would be good candidates for the development of fermented foods bio-fortified with both dextrans and riboflavin. Moreover, this is the first report of riboflavin and dextran production by L. falkenbergense.This research was funded by the Spanish Ministry of Science, Innovation and Universities, (grants RTI2018-097114-B-I00 and PCIN-2017-075), by the Basque Government Industry and Education Department (grant PIBA_2020_1_0032) and by the University of the Basque Country (General Grant to Research Groups (GIU 19/014))

HER2 expression in cervical cancer as a potential therapeutic target

BACKGROUND: Trastuzumab, a humanized monoclonal antibody against the HER2 receptor is currently being used in breast and other tumor types. Early studies have shown that a variable proportion of cervical carcinoma tumors overexpress the HER2 receptor as evaluated by diverse techniques and antibodies. Currently it is known that a tumor response to trastuzumab strongly correlates with the level of HER2 expression evaluated by the Hercep Test, thus, it seems desirable to evaluate the status of expression of this receptor using the FDA-approved Hercep Test and grading system to gain insight in the feasibility of using trastuzumab in cervical cancer patients. METHODS: We analyzed a series of cervical cancer cell lines, the primary tumors of 35 cases of cervical cancer patients and four recurrent cases, with the Hercep Test in order to establish whether this tumor type overexpress HER2 at level of 2+/3+ as trastuzumab is currently approved for breast cancer having such level of expression. RESULTS: The results indicate that only 1 out of 35 primary tumors cases overexpress the receptor at this level, however, two out of four recurrent tumors that tested negative at diagnosis shifted to Hercep Test 2+ and 3+ respectively. CONCLUSIONS: The low frequency of expression in primary cases suggests that trastuzumab could have a limited value for the primary management of cervical cancer patients, however, the finding of "conversion" to Hercep Test 2+ and 3+ of recurrent tumors indicates the need to further evaluate the expression of HER2 in the metastatic and recurrent cases

Continuous fungal treatment of non-sterile veterinary hospital effluent: pharmaceuticals removal and microbial community assessment

Source point treatment of effluents with a high load of pharmaceutical active compounds (PhACs), such as hospital wastewater, is a matter of discussion among the scientific community. Fungal treatments have been reported to be successful in degrading this type of pollutants and, therefore, the white-rot fungus Trametes versicolor was applied for the removal of PhACs from veterinary hospital wastewater. Sixty-six percent removal was achieved in a non-sterile batch bioreactor inoculated with T. versicolor pellets. On the other hand, the study of microbial communities by means of DGGE and phylogenetic analyses led us to identify some microbial interactions and helped us moving to a continuous process. PhAC removal efficiency achieved in the fungal treatment operated in non-sterile continuous mode was 44 % after adjusting the C/N ratio with respect to the previously calculated one for sterile treatments. Fungal and bacterial communities in the continuous bioreactors were monitored as well.Authors want to acknowledge the UAB veterinary hospital staff for their kind permission and help for the samplings. This work has been funded by the Spanish Ministry of Economy and Competitiveness and FEDER (projects CTM2013-48545-C2 and AIB2010PT-00169) and supported by the Generalitat de Catalunya (Consolidated Research Groups 2014-SGR-476 and 2014-SGR-291). The Department of Chemical Engineering of the Universitat Autonoma de Barcelona (UAB) is a member of the Xarxa de Referencia en Biotecnologia de la Generalitat de Catalunya. M. Badia-Fabregat and D. Lucas acknowledge the predoctoral grants from UAB and from the Spanish Ministry of Education, Culture and Sports (AP-2010-4926), respectively. The authors also thank the Portuguese Foundation for Science and Technology (FCT) Strategic Project PEst-OE/EQB/LA0023/2013, Project FCOMP-01-0124-FEDER-027462 co-funded by Operational Competitiveness Programme, FEDER, and Project "BioEnv-Biotechnology and Bioengineering for a sustainable world," REF. NORTE-07-0124-FEDER-000048, co-funded by Programa Operacional Regional do Norte (ON.2 - O Novo Norte), QREN, FEDER

A Proof-Of-Principle Study of Epigenetic Therapy Added to Neoadjuvant Doxorubicin Cyclophosphamide for Locally Advanced Breast Cancer

BACKGROUND: Aberrant DNA methylation and histone deacetylation participate in cancer development and progression; hence, their reversal by inhibitors of DNA methylation and histone deacetylases (HDACs) is at present undergoing clinical testing in cancer therapy. As epigenetic alterations are common to breast cancer, in this proof-of-concept study demethylating hydralazine, plus the HDAC inhibitor magnesium valproate, were added to neoadjuvant doxorubicin and cyclophosphamide in locally advanced breast cancer to assess their safety and biological efficacy. METHODOLOGY: This was a single-arm interventional trial on breast cancer patients (ClinicalTrials.gov Identifier: NCT00395655). After signing informed consent, patients were typed for acetylator phenotype and then treated with hydralazine at 182 mg for rapid-, or 83 mg for slow-acetylators, and magnesium valproate at 30 mg/kg, starting from day –7 until chemotherapy ended, the latter consisting of four cycles of doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) every 21 days. Core-needle biopsies were taken from primary breast tumors at diagnosis and at day 8 of treatment with hydralazine and valproate. MAIN FINDINGS: 16 patients were included and received treatment as planned. All were evaluated for clinical response and toxicity and 15 for pathological response. Treatment was well-tolerated. The most common toxicity was drowsiness grades 1–2. Five (31%) patients had clinical CR and eight (50%) PR for an ORR of 81%. No patient progressed. One of 15 operated patients (6.6%) had pathological CR and 70% had residual disease <3 cm. There was a statistically significant decrease in global 5(m)C content and HDAC activity. Hydralazine and magnesium valproate up- and down-regulated at least 3-fold, 1,091 and 89 genes, respectively. CONCLUSIONS: Hydralazine and magnesium valproate produce DNA demethylation, HDAC inhibition, and gene reactivation in primary tumors. Doxorubicin and cyclophosphamide treatment is safe, well-tolerated, and appears to increase the efficacy of chemotherapy. A randomized phase III study is ongoing to support the efficacy of so-called epigenetic or transcriptional cancer therapy

Fungal diversity notes 929–1035: taxonomic and phylogenetic contributions on genera and species of fungi

This article is the ninth in the series of Fungal Diversity Notes, where 107 taxa distributed in three phyla, nine classes, 31 orders and 57 families are described and illustrated. Taxa described in the present study include 12 new genera, 74 new species, three new combinations, two reference specimens, a re-circumscription of the epitype, and 15 records of sexualasexual morph connections, new hosts and new geographical distributions. Twelve new genera comprise Brunneofusispora, Brunneomurispora, Liua, Lonicericola, Neoeutypella, Paratrimmatostroma, Parazalerion, Proliferophorum, Pseudoastrosphaeriellopsis, Septomelanconiella, Velebitea and Vicosamyces. Seventy-four new species are Agaricus memnonius, A. langensis, Aleurodiscus patagonicus, Amanita flavoalba, A. subtropicana, Amphisphaeria mangrovei, Baorangia major, Bartalinia kunmingensis, Brunneofusispora sinensis, Brunneomurispora lonicerae, Capronia camelliaeyunnanensis, Clavulina thindii, Coniochaeta simbalensis, Conlarium thailandense, Coprinus trigonosporus, Liua muriformis, Cyphellophora filicis, Cytospora ulmicola, Dacrymyces invisibilis, Dictyocheirospora metroxylonis, Distoseptispora thysanolaenae, Emericellopsis koreana, Galiicola baoshanensis, Hygrocybe lucida, Hypoxylon teeravasati, Hyweljonesia indica, Keissleriella caraganae, Lactarius olivaceopallidus, Lactifluus midnapurensis, Lembosia brigadeirensis, Leptosphaeria urticae, Lonicericola hyaloseptispora, Lophiotrema mucilaginosis, Marasmiellus bicoloripes, Marasmius indojasminodorus, Micropeltis phetchaburiensis, Mucor orantomantidis, Murilentithecium lonicerae, Neobambusicola brunnea, Neoeutypella baoshanensis, Neoroussoella heveae, Neosetophoma lonicerae, Ophiobolus malleolus, Parabambusicola thysanolaenae, Paratrimmatostroma kunmingensis, Parazalerion indica, Penicillium dokdoense, Peroneutypa mangrovei, Phaeosphaeria cycadis, Phanerochaete australosanguinea, Plectosphaerella kunmingensis, Plenodomus artemisiae, P. lijiangensis, Proliferophorum thailandicum, Pseudoastrosphaeriellopsis kaveriana, Pseudohelicomyces menglunicus, Pseudoplagiostoma mangiferae, Robillarda mangiferae, Roussoella elaeicola, Russula choptae, R. uttarakhandia, Septomelanconiella thailandica, Spencermartinsia acericola, Sphaerellopsis isthmospora, Thozetella lithocarpi, Trechispora echinospora, Tremellochaete atlantica, Trichoderma koreanum, T. pinicola, T. rugulosum, Velebitea chrysotexta, Vicosamyces venturisporus, Wojnowiciella kunmingensis and Zopfiella indica. Three new combinations are Baorangia rufomaculata, Lanmaoa pallidorosea and Wojnowiciella rosicola. The reference specimens of Canalisporium kenyense and Tamsiniella labiosa are designated. The epitype of Sarcopeziza sicula is re-circumscribed based on cyto- and histochemical analyses. The sexual-asexual morph connection of Plenodomus sinensis is reported from ferns and Cirsium for the first time. In addition, the new host records and country records are Amanita altipes, A. melleialba, Amarenomyces dactylidis, Chaetosphaeria panamensis, Coniella vitis, Coprinopsis kubickae, Dothiorella sarmentorum, Leptobacillium leptobactrum var. calidus, Muyocopron lithocarpi, Neoroussoella solani, Periconia cortaderiae, Phragmocamarosporium hederae, Sphaerellopsis paraphysata and Sphaeropsis eucalypticola