Effects of temperature, ammonium and glucose concentrations on yeast growth in a model wine system

In enology, alcoholic fermentation is a complex process involving several mechanisms. Slow and incomplete alcoholic fermentation is a chronic problem for the wine industry and factors leading to sluggish and stuck fermentations have been extensively studied and reviewed. The most studied cause of sluggish and stuck fermentation is the nitrogen content limitation. Nevertheless, other factors, such as temperature of fermentation and sugar concentration can affect the growth of yeasts. In this study we modelled the yeast growth‐cycle in wine model system as a function of temperature, sugar and ammonium concentrations; the individual effects and the interaction of these factors were analysed by means of a quadratic response surface methodology. Cell concentrations and weight loss were monitored in the whole wine fermentation process. The results of central composite design show that lower is the availability of nitrogen, higher is the cell growth rate; moreover, initial nitrogen concentration also influences survival time of Saccharomyces cerevisiae.     

Electrocortical desynchronization after microinfusion of kainic acid into the locus coeruleus in rats

CD-1, a genetically-engineered CHO cell line, was cultivated with a Biosilon microcarrier culture system. We successfully cultivated CD-1 cells to a very high density (over 1 x 10(7) cells/ml). Prourokinase was stably secreted at about 180 IU/10(6) cells/24 h. Experiments showed that CD-1 cells growing on Biosilon microcarriers were able to spontaneously release from the microcarriers, then reattach and proliferate on fresh microcarriers. This makes it very easy to scale up production. The microcarriers could be reused several times without affecting adhesion, proliferation and prourokinase secretion. With CM-PECC membrane radial flow chromatography and MPG chromatography, the prourokinase in conditioned medium could be purified to a specific activity of 1 x 10(5) IU/mg of protein. The purification factor was about 600 fold, and approximately 90% of the biological activity was recovered.     

Chemical and Physical Signals Mediating Conspecific and Heterospecific Aggregation Behavior of First Instar Stink Bugs

We investigated cues that mediate the aggregation behavior of immature pentatomid bugs by using nymphs of six different pentatomid bug species (Nezara viridula, Acrosternum hilare, Chlorochroa ligata, Chlorochroa sayi, Thyanta pallidovirens, and Euschistus conspersus). When first instars of any two species were put together in a Petri dish, they readily formed heterospecific aggregations similar to their natural conspecific aggregations. The chemical profiles of first and second instar nymphs of each species were determined by solvent extraction with pentane, followed by GC-MS analysis. Immature bugs of the different species had some compounds in common, and some that were more species specific. Within a species, there were distinct differences in the profiles of compounds extracted from first and second instars. Bugs did not aggregate around untreated polysulfone beads (1 mm diam) that were glued together in groups approximating bug egg masses, suggesting that tactile cues alone were insufficient to induce aggregation. Furthermore, when tested over a range of doses, groups of polysulfone beads treated with crude whole-body extracts of bugs did not induce or maintain aggregations. However, first instar N. viridula nymphs did respond to beads treated with two of the three major components of bug extracts. 4-Oxo-(E)-2-decenal induced significant aggregations at two doses, whereas tridecane, the major component in extracts from all six species, did not, and (E)-2-decenal was repellent. The repellence of (E)-2-decenal may explain why we and previous researchers were unable to induce aggregations of first instar N. viridula using whole-body extracts.     

Adaptive course generation through learning styles representation

This paper presents an approach to automatic course generation and student modeling. The method has been developed during the European funded projects Diogene and Intraserv, focused on the construction of an adaptive e-learning platform. The aim of the platform is the automatic generation and personalization of courses, taking into account pedagogical knowledge on the didactic domain as well as statistic information on both the student’s knowledge degree and learning preferences. Pedagogical information is described by means of an innovative methodology suitable for effective and efficient course generation and personalization. Moreover, statistic information can be collected and exploited by the system in order to better describe the student’s preferences and learning performances. Learning material is chosen by the system matching the student’s learning preferences with the learning material type, following a pedagogical approach suggested by Felder and Silverman. The paper discusses how automatic learning material personalization makes it possible to facilitate distance learning access to both able-bodied and disabled people. Results from the Diogene and Intraserv evaluation are reported and discussed.     

Modeling Self-Rollable Elastomeric Films for Building Bioinspired Hierarchical 3D Structures

In this work, an innovative model is proposed as a design tool to predict both the inner and outer radii in rolled structures based on polydimethylsiloxane bilayers. The model represents an improvement of Timoshenko’s formula taking into account the friction arising from contacts between layers arising from rolling by more than one turn, hence broadening its application field towards materials based on elastomeric bilayers capable of large deformations. The fabricated structures were also provided with surface topographical features that would make them potentially usable in different application scenarios, including cell/tissue engineering ones. The bilayer design parameters were varied, such as the initial strain (from 20 to 60%) and the bilayer thickness (from 373 to 93 µm). The model matched experimental data on the inner and outer radii nicely, especially when a high friction condition was implemented in the model, particularly reducing the error below 2% for the outer diameter while varying the strain. The model outperformed the current literature, where self-penetration is not excluded, and a single value of the radius of spontaneous rolling is used to describe multiple rolls. A complex 3D bioinspired hierarchical elastomeric microstructure made of seven spirals arranged like a hexagon inscribed in a circumference, similar to typical biological architectures (e.g., myofibrils within a sarcolemma), was also developed. In this case also, the model effectively predicted the spirals’ features (error smaller than 18%), opening interesting application scenarios in the modeling and fabrication of bioinspired materials.     

Limited Accuracy of Pan-Trk Immunohistochemistry Screening for NTRK Rearrangements in Follicular-Derived Thyroid Carcinoma

Patients with advanced thyroid cancer harboring NTRK rearrangements can be treated with highly effective selective inhibitors. Immunohistochemistry (IHC) analysis, to detect Trk protein expression, represents an appealing screening strategy for NTRK rearrangements, but its efficacy has been poorly explored in thyroid cancer. The aim of this study is to investigate the diagnostic utility of Trk IHC in the identification of NTRK rearrangements. A series of 26 follicular-derived thyroid tumors, positive for NTRK rearrangements, and 28 NTRK fusion-negative controls were retrospectively analyzed by IHC using the pan-Trk monoclonal antibody (clone {"type":"entrez-protein","attrs":{"text":"EPR17341","term_id":"523383444","term_text":"EPR17341"}}EPR17341) on the Ventana system. Area under the curve (AUC), sensitivity and specificity were calculated by ROC analysis. Trk expression was detected in 25 samples, including 22 out of the 26 NTRK-rearranged (84.6%) and three out of 28 NTRK-negative samples (10.7%). Four out of twenty-six NTRK-rearranged thyroid tumors were negative for Trk expression (15.4%), all carrying the ETV6/NTRK3 fusion. The AUC, sensitivity and specificity were 0.87, 0.85 and 0.89, respectively. A screening based on IHC analysis showed limited sensitivity and specificity in the identification of NTRK-rearranged tumors. Since falsely negative results could preclude the administration of effective targeted drugs, alternative detection strategies should be considered for thyroid cancer.     

NSCLC as the Paradigm of Precision Medicine at Its Finest: The Rise of New Druggable Molecular Targets for Advanced Disease

Standard treatment for advanced non-small cell lung cancer (NSCLC) historically consisted of systemic cytotoxic chemotherapy until the early 2000s, when precision medicine led to a revolutionary change in the therapeutic scenario. The identification of oncogenic driver mutations in EGFR, ALK and ROS1 rearrangements identified a subset of patients who largely benefit from targeted agents. However, since the proportion of patients with druggable alterations represents a minority, the discovery of new potential driver mutations is still an urgent clinical need. We provide a comprehensive review of the emerging molecular targets in NSCLC and their applications in the advanced setting.     

Tissue Engineering and Regenerative Medicine in Pediatric Urology: Urethral and Urinary Bladder Reconstruction

In the case of pediatric urology there are several congenital conditions, such as hypospadias and neurogenic bladder, which affect, respectively, the urethra and the urinary bladder. In fact, the gold standard consists of a urethroplasty procedure in the case of urethral malformations and enterocystoplasty in the case of urinary bladder disorders. However, both surgical procedures are associated with severe complications, such as fistulas, urethral strictures, and dehiscence of the repair or recurrence of chordee in the case of urethroplasty, and metabolic disturbances, stone formation, urine leakage, and chronic infections in the case of enterocystoplasty. With the aim of overcoming the issue related to the lack of sufficient and appropriate autologous tissue, increasing attention has been focused on tissue engineering. In this review, both the urethral and the urinary bladder reconstruction strategies were summarized, focusing on pediatric applications and evaluating all the biomaterials tested in both animal models and patients. Particular attention was paid to the capability for tissue regeneration in dependence on the eventual presence of seeded cell and growth factor combinations in several types of scaffolds. Moreover, the main critical features needed for urinary tissue engineering have been highlighted and specifically focused on for pediatric application.     

A Short ERAP2 That Binds IRAP Is Expressed in Macrophages Independently of Gene Variation

The M1 zinc metalloproteases ERAP1, ERAP2, and IRAP play a role in HLA-I antigen presentation by refining the peptidome either in the ER (ERAP1 and ERAP2) or in the endosomes (IRAP). They have also been entrusted with other, although less defined, functions such as the regulation of the angiotensin system and blood pressure. In humans, ERAP1 and IRAP are commonly expressed. ERAP2 instead has evolved under balancing selection that maintains two haplotypes, one of which undergoing RNA splicing leading to nonsense-mediated decay and loss of protein. Hence, likewise in rodents, wherein the ERAP2 gene is missing, about a quarter of the human population does not express ERAP2. We report here that macrophages, but not monocytes or other mononuclear blood cells, express and secrete an ERAP2 shorter form independent of the haplotype. The generation of this “short” ERAP2 is due to an autocatalytic cleavage within a distinctive structural motif and requires an acidic micro-environment. Remarkably, ERAP2 “short” binds IRAP and the two molecules are co-expressed in the endosomes as well as in the cell membrane. Of note, the same phenomenon could be observed in some cancer cells. These data prompt us to reconsider the role of ERAP2, which might have been maintained in humans due to fulfilling a relevant function in its “short” form.