The occurrence of fungi, yeasts and bacteria in the air of a Spanish winery during vintage

This research studies the presence of microorganisms of enological interest (yeasts, bacteria and molds) and their evolution in the air of a wine cellar. The samples were taken throughout the winemaking campaign (September-December) in a winery of the D.O.Ca. Rioja, Spain. They were collected using an airIDEAL atmosphere sampler from Biomerieux. For the isolation, specific selective media were used for each group of microorganisms. The results obtained indicate that the presence in the winery air of the various different microorganisms studied is directly related to the winemaking processes that are taking place in the winery. Thus, the number of molds present decreases once grapes have ceased to be brought into the winery. The maximum number of yeasts in the air is found when all the vats in the cellar are fermenting, while the lactic bacteria are not detected until the first malolactic fermentation begins. The species of yeasts and molds identified are also related to the winemaking processes. The coincidence of strains of Saccharomyces cerevisiae among those present in the vats during alcoholic fermentation and those isolated from the air, confirms the role of the latter as a transmitter of microorganisms.     

Enhanced bactericidal effect of enterocin AS-48 in combination with high-intensity pulsed-electric field treatment against Salmonella enterica in apple juice

The effect of the broad spectrum cyclic antimicrobial peptide enterocin AS-48 combination with high-intensity pulsed-electric field (HIPEF) treatment (35 kV/cm, 150 Hz, 4 micros and bipolar mode) was tested on Salmonella enterica CECT 915 in apple juice. A response surface methodology was applied to study the bactericidal effects of the combined treatment. The process variables were AS-48 concentration, temperature, and HIPEF treatment time. While treatment with enterocin AS-48 alone up to 60 microg/ml had no effect on the viability of S. enterica in apple juice, an increased bactericidal activity was observed in combination with HIPEF treatments. Survival fraction was affected by treatment time, enterocin AS48 concentration and treatment temperature. The combination of 100 micros of HIPEF treatment, 30 microg/ml of AS-48, and temperature of 20 degrees C resulted in the lowest inactivation, with only a 1.2-log reduction. The maximum inactivation of 4.5-log cycles was achieved with HIPEF treatment for 1000 micros in combination with 60 microg/ml of AS-48 and a treatment temperature of 40 degrees C. Synergism between enterocin AS-48 and HIPEF treatment depended on the sequence order application, since it was observed only when HIPEF was applied in the presence of previously-added bacteriocin. The combined treatment could improve the safety of freshly-made apple juice against S. enterica transmission.     

Identification of miR-20a-5p as Robust Normalizer for Urine microRNA Studies in Renal Cell Carcinoma and a Profile of Dysregulated microRNAs

Renal cell carcinoma (RCC) is the third most frequent urinary malignancy and one of the most lethal. Current diagnostic and follow-up techniques are harmful and unspecific in low-grade tumors. Novel minimally invasive markers such as urine microRNAs (miRNAs) are under study. However, discrepancies arise among studies in part due to lack of consent regarding normalization. We aimed to identify the best miRNA normalizer for RCC studies performed in urine samples together with a miRNA profile with diagnostic value and another for follow-up. We evaluated the performance of 120 candidate miRNAs in the urine of 16 RCC patients and 16 healthy controls by RT-qPCR followed by a stability analysis with RefFinder. In this screening stage, miR-20a-5p arose as the most stably expressed miRNA in RCC and controls, with a good expression level. Its stability was validated in an independent cohort of 51 RCC patients and 32 controls. Using miR-20a-5p as normalizer, we adjusted and validated a diagnostic model for RCC with three miRNAs (miR-200a-3p, miR-34a-5p and miR-365a-3p) (AUC = 0.65; Confidence Interval 95% [0.51, 0.79], p = 0.043). let-7d-5p and miR-205-5p were also upregulated in patients compared to controls. Comparing RCC samples before surgery and fourteen weeks after, we identified let-7d-5p, miR-152-3p, miR-30c-5p, miR-362-3p and miR-30e-3p as potential follow-up profile for RCC. We identified validated targets of most miRNAs in the renal cell carcinoma pathway. This is the first study that identifies a robust normalizer for urine RCC miRNA studies, miR-20a-5p, which may allow the comparison of future studies among laboratories. Once confirmed in a larger independent cohort, the miRNAs profiles identified may improve the non-invasive diagnosis and follow-up of RCC.     

Leukemia-Induced Cellular Senescence and Stemness Alterations in Mesenchymal Stem Cells Are Reversible upon Withdrawal of B-Cell Acute Lymphoblastic Leukemia Cells

Leukemic cell growth in the bone marrow (BM) induces a very stressful condition. Mesenchymal stem cells (MSC), a key component of this BM niche, are affected in several ways with unfavorable consequences on hematopoietic stem cells favoring leukemic cells. These alterations in MSC during B-cell acute lymphoblastic leukemia (B-ALL) have not been fully studied. In this work, we have compared the modifications that occur in an in vitro leukemic niche (LN) with those observed in MSC isolated from B-ALL patients. MSC in this LN niche showed features of a senescence process, i.e., altered morphology, increased senescence-associated β-Galactosidase (SA-βGAL) activity, and upregulation of p53 and p21 (without p16 expression), cell-cycle arrest, reduced clonogenicity, and some moderated changes in stemness properties. Importantly, almost all of these features were found in MSC isolated from B-ALL patients. These alterations rendered B-ALL cells susceptible to the chemotherapeutic agent dexamethasone. The senescent process seems to be transient since when leukemic cells are removed, normal MSC morphology is re-established, SA-βGAL expression is diminished, and MSC are capable of re-entering cell cycle. In addition, few cells showed low γH2AX phosphorylation that was reduced to basal levels upon cultivation. The reversibility of the senescent process in MSC must impinge important biological and clinical significance depending on cell interactions in the bone marrow at different stages of disease progression in B-ALL.     

Oral Selective Estrogen Receptor Degraders (SERDs) as a Novel Breast Cancer Therapy: Present and Future from a Clinical Perspective

Estrogen receptor-positive (ER+) is the most common subtype of breast cancer. Endocrine therapy is the fundamental treatment against this entity, by directly or indirectly modifying estrogen production. Recent advances in novel compounds, such as cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), or phosphoinositide 3-kinase (PI3K) inhibitors have improved progression-free survival and overall survival in these patients. However, some patients still develop endocrine resistance after or during endocrine treatment. Different underlying mechanisms have been identified as responsible for endocrine treatment resistance, where ESR1 gene mutations are one of the most studied, outstanding from others such as somatic alterations, microenvironment involvement and epigenetic changes. In this scenario, selective estrogen receptor degraders/downregulators (SERD) are one of the weapons currently in research and development against aromatase inhibitor- or tamoxifen-resistance. The first SERD to be developed and approved for ER+ breast cancer was fulvestrant, demonstrating also interesting activity in ESR1 mutated patients in the second line treatment setting. Recent investigational advances have allowed the development of new oral bioavailable SERDs. This review describes the evolution and ongoing studies in SERDs and new molecules against ER, with the hope that these novel drugs may improve our patients’ future landscape.     

Effect of metallurgical evolution during post-weld aging treatment on localised corrosion of resistance spot welding joints of A286 superalloy

The combined effect of resistance spot welding and precipitation hardening on the localised corrosion of A286 superalloy is studied. The specimens tested by double loop electrochemical potentiokinetic reactivation were welded in the solution treated condition, and then subjected to different precipitation hardening treatments. For both base metal and weld nugget, the maximum localised corrosion is reached when η phase is clearly observable. The fact that the localised corrosion resistance of weld nugget is different from that shown by base metal may be explained by the segregation of Ni and Ti towards the interdendritic region of weld nugget (studied by using scanning electron microscope/energy dispersive X-ray analysis).     

Waste waters from the leachate of mushroom as vine foliar treatments: influence on grape volatile composition over two consecutive seasons

Edible mushrooms production presents a potential problem for the environment, due to the large amount of waste generated. These wastes contain nitrogenous matter, which could be used as biostimulant in plants. The aim of this work was to study the effect of waste waters, from the mushroom production process, applied at veraison and 1 week later to grapevine leaves, on grape volatile compounds over two vintages. The results evidenced that mushroom water treatment decreased the grape content of certain terpenoids, C₁₃ norisoprenoids, benzenoid compounds and esters, increasing C6 compounds content during the first season. Treated mushroom water application slightly affected grape volatile composition. This was the treatment that least affected the content of grape volatile composition. Few differences were found after the biostimulation during the second vintage. The season was the dominant factor of grape volatile content variation compared to the treatment and their interaction.     

Distinct annexin subfamilies in plants and protists diverged prior to animal annexins and from a common ancestor

Annexin homologues in the kingdoms of Planta and Protista were characterized by molecular sequence analysis to determine their phylogenetic and structural relationship with annexins of Animalia. Sequence fragments from 19 plant annexins were identified in sequence databases and composite sequences were also assembled from expressed sequence tags for Arabidopsis thaliana. Length differences in protein aminotermini and evidence for unique exon splice sites indicated that plant annexins were distinct from those of animals. A third annexin gene of Giardia lamblia (Anx21-Gla) was identified as a distant relative to other protist annexins and to those of higher eukaryotes, thus providing a suitable outgroup for evolutionary reconstruction of the family tree. Rooted evolutionary trees portrayed protist, plant, and Dictyostelium annexins as early, monophyletic ramifications prior to the appearance of closely related animal annexin XIII. Molecular phylogenetic analyses of DNA and protein sequence alignments revealed at least seven separate plant subfamilies, represented by Anx18 (alfalfa, previously classified), Anx22 (thale cress), Anx23 (thale cress, cotton, rape and cabbage), Anx24 (bell pepper and tomato p34), Anx25 (strawberry, horseradish, pea, soybean, and castor bean), Anx26-Zma, and Anx27-Zma (maize). Other unique subfamilies may exist for rice, tomato p35, apple, and celery annexins. Consensus sequences compiled for each eukaryotic kingdom showed some breakdown of the "annexin-fold" motif in repeats 2 and 3 of protist and plant annexins and a conserved codon deletion in repeat 3 of plants. The characterization of distinct annexin genes in plants and protists reflects their comparable diversity among animal species and offers alternative models for the comparative study of structure-function relationships within this important gene family.     

3D Printing of a Thermo‐ and Solvatochromic Composite Material Based on a Cu(II)–Thymine Coordination Polymer with Moisture Sensing Capabilities

This work presents the fabrication of 3D‐printed composite objects based on copper(II) 1D coordination polymer ( CP1 ) decorated with thymine along its chains with potential utility as an environmental humidity sensor and as a water sensor in organic solvents. This new composite object has a remarkable sensitivity, ranging from 0.3% to 4% of water in organic solvents. The sensing capacity is related to the structural transformation due to the loss of water molecules that CP1 undergoes with temperature or by solvent molecules' competition, which induces significant change in color simultaneously. The CP1 and 3D printed materials are stable in air over 1 year and also at biological pHs (5–7), therefore suggesting potential applications as robust colorimetric sensors. These results open the door to generate a family of new 3D printed materials based on the integration of multifunctional coordination polymers with organic polymers.