Evaluation of a novel human IgG1 anti-claudin3 antibody that specifically recognizes its aberrantly localized antigen in ovarian cancer cells and that is suitable for selective drug delivery

Membrane protein claudin3 has been recently suggested as a marker for biologically aggressive tumors and a possible target for the therapeutic delivery of active anti-cancer compounds. Claudin3-binding molecules such as the Clostridium perfringens enterotoxin (CPE), CPE-related molecules, and murine and chimeric antibodies have shown promising antitumor efficacy in preclinical oncological settings. We first engineered a fully human anti-claudin3 IgG1 antibody (IgGH6) by fusing the human IgG1 Fc-domain to the anti-claudin3 scFvH6 previously isolated from a pre-immune phage display library. The construct was expressed in mammalian cells and specifically targeted claudin3 endogenously expressed on the surface of different human ovarian cancer cell lines. No detectable cross-reactivity with other homologous claudins was observed. The epitope recognized by IgGH6 is located within the minor extracellular domain of claudin3 and becomes accessible only in tumor cells characterized by incomplete junction formation. Confocal microscopy experiments demonstrated that IgGH6 was actively internalized in tumor cells after binding to native claudin3 and co-localized, likely within intracellular vesicles, with the C-CPE peptide. Preliminary results indicate that IgGH6 accumulated in vivo in free claudin3 ovarian carcinoma xenografts. For its selective uptake in tumor cells and its human nature, IgGH6 represents a valuable candidate for antibody-drug conjugate therapeutic applications in ovarian cancer patients

A characterization theorem for equivariant networks with point-wise activations

Equivariant neural networks have shown improved performance, expressiveness and sample complexity on symmetrical domains. But for some specific symmetries, representations, and choice of coordinates, the most common point-wise activations, such as ReLU, are not equivariant, hence they cannot be employed in the design of equivariant neural networks. The theorem we present in this paper describes all possibile combinations of representations, choice of coordinates and point-wise activations to obtain an equivariant layer, generalizing and strengthening existing characterizations. Notable cases of practical relevance are discussed as corollaries. Indeed, we prove that rotation-equivariant networks can only be invariant, as it happens for any network which is equivariant with respect to connected compact groups. Then, we discuss implications of our findings when applied to important instances of equivariant networks. First, we completely characterize permutation equivariant networks such as Invariant Graph Networks with point-wise nonlinearities and their geometric counterparts, highlighting a plethora of models whose expressive power and performance are still unknown. Second, we show that feature spaces of disentangled steerable convolutional neural networks are trivial representations

A Characterization Theorem for Equivariant Networks with Point-wise Activations

Equivariant neural networks have shown improved performance, expressiveness and sample complexity on symmetrical domains. But for some specific symmetries, representations, and choice of coordinates, the most common point-wise activations, such as ReLU, are not equivariant, hence they cannot be employed in the design of equivariant neural networks. The theorem we present in this paper describes all possible combinations of finite-dimensional representations, choice of coordinates and point-wise activations to obtain an exactly equivariant layer, generalizing and strengthening existing characterizations. Notable cases of practical relevance are discussed as corollaries. Indeed, we prove that rotation-equivariant networks can only be invariant, as it happens for any network which is equivariant with respect to connected compact groups. Then, we discuss implications of our findings when applied to important instances of exactly equivariant networks. First, we completely characterize permutation equivariant networks such as Invariant Graph Networks with point-wise nonlinearities and their geometric counterparts, highlighting a plethora of models whose expressive power and performance are still unknown. Second, we show that feature spaces of disentangled steerable convolutional neural networks are trivial representations.Comment: Accepted at the 12th International Conference on Learning Representations (ICLR 2024

Short-Term CO2 Treatment of Harvested Grapes (Vitis vinifera L., cv. Trebbiano) before Partial Dehydration Affects Berry Secondary Metabolism and the Aromatic Profile of the Resulting Wine

High CO2 concentrations applied to harvested horticultural products can modify primary and secondary metabolism. This work reports the metabolic responses to short-term CO2 treatments of white-skinned grapes (cv Trebbiano) undergoing postharvest partial dehydration. The influence of CO2 treatments on the aroma profile of the derived sweet wine was also assessed. Harvested grapes were treated with gaseous CO2 (30%) or air (control) for 24 h and then dehydrated (about 45% of weight loss) before vinification. Lipophilic and phenolic compounds of grape skin and the wine aroma profile were analyzed. In CO2-treated berries, the lipophilic and phenolic compounds decreased at a reduced and faster rate, respectively, during dehydration. Aroma profile of wine from CO2-treated grapes showed a slight but significantly higher content of glycosylated C13 and terpene compounds, and a decrease/absence of free acids, vanillin derivates and other phenol volatiles. The higher content of volatile alcohols in wine from treated berries suggests that the alcoholic fermentation was triggered. CO2 application before the withering process of Trebbiano grapes affects the aroma profile of the resulting wine by altering the free:glycosylated volatiles ratio. This study provides information on the possible use of CO2 as metabolic elicitor to modulate the aroma profile of the resulting wines obtained after grape dehydratio

Curso - Modelagem de Análise de Impacto Regulatório: uma abordagem prática

Programa do curso contendo objetivo, ementa, metodologia de ensino e avaliação. Plano de aula, referências bibliográficas e currículos dos professores. Slides referentes às aulas 1, 2, 3, 4, 5, 6 e 7.1. Programa do Curso: Documento em PDF, 4 páginas, contendo as informações sobre o curso.2. Apresentação: Documento em PDF, 24 páginas, contendo slides referentes às aulas 1.3. Apresentação: Documento em PDF, 25 páginas, contendo os slides referentes à aula 2.4. Apresentação: Documento em PDF, 22 páginas, contendo os slides referentes à aula 3.5. Apresentação: Documento em PDF, 32 páginas contendo slides referentes à aula 4.6. Apresentação: Documento em PDF, 26 páginas, contendo os slides referentes à aula 5.7. Apresentação: Documento em PDF, 20 páginas, contendo os slides referentes à aula 6.8. Apresentação: Documento em PDF, 19 páginas, contendo os slides referentes à aula 7.Gestão Estratégica. PlanejamentoPolíticas Pública

The dominant allele Aft induces a shift from flavonol to anthocyanin production in response to UV-B radiation in tomato fruit

The introgression of the A ft allele into domesticated tomato induced a shift from flavonol to anthocyanin production in response to UV-B radiation, while the hp - 1 allele negatively influenced the response of flavonoid biosynthesis to UV-B. Introgression of the dominant allele Anthocyanin fruit (Aft) from Solanum chilense induces anthocyanin accumulation in the peel of tomato (Solanum lycopersicum L.) fruit. UV-B radiation can influence plant secondary metabolism regulating the expression of several genes, among which those involved in flavonoid biosynthesis. Here, we investigated whether post-harvest UV-B treatment could up-regulate flavonoid production in tomato fruits and whether the Aft allele could affect flavonoid biosynthesis under UV-B radiation. Mature green fruits of an anthocyanin-rich tomato mutant line (SA206) and of its wild-type reference, cv. Roma, were daily subjected to post-harvest UV-B treatment until full ripening. Up-regulation of CHS and CHI transcription by UV-B treatment induced flavonoid accumulation in the peel of cv. Roma. Conversely, UV-B decreased the total flavonoid content and CHS transcript levels in the SA206 peel. SA206 being a double mutant containing also hp-1 allele, we investigated also the behavior of hp-1 fruit. The decreased peel flavonoid accumulation and gene transcription in response to UV-B suggest that hp-1 allele is involved in the marked down-regulation of the flavonoid biosynthesis observed in SA206 fruit. Interestingly, in SA206, UV-B radiation promoted the synthesis of delphinidin, petunidin, and malvidin by increasing F3'5'H and DFR transcription, but it decreased rutin production, suggesting a switch from flavonols to anthocyanins. Finally, although UV-B radiation does not reach the inner fruit tissues, it down-regulated flavonoid biosynthesis in the flesh of both genotypes. This study provides, for the first time, evidence that the presence of the functional Aft allele, under UV-B radiation, redirects flavonoid synthesis towards anthocyanin production and suggests that the hp-1 allele negatively influences the response of flavonoid biosynthesis to UV-B

Gravity effects on lower limb perfusion observed during a series of parabolic flights

The present observational study simultaneously measured four key factors (arterial oxygenation, superficial tissue oxygenation, peripheral skin temperature, toe systolic pressure) to determine the impact on lower limb perfusion in altered gravity conditions. 24 healthy test subjects (16 male, 8 female) took part onboard a series of parabolic flights. When comparing lower limb perfusion values to 1G (control/Earth’s gravity) the study found: 1) no significant difference between arterial oxygenation values in hyper or microgravity was detected when using a pulse oximeter; 2) a significant difference in superficial tissue oxygenation in hyper and microgravity was detected by white light spectroscopy; 3) a significant difference in skin temperature of the foot was detected by thermography in hyper and microgravity; 4) an insufficient sample could be obtained for toe systolic pressure. Reduction in superficial tissue oxygenation and peripheral skin temperature in microgravity compared to 1G, potentially suggests a reduction in blood flow. White light spectroscopy and thermography devices demonstrated they functioned as usual in altered gravity conditions potentially offering a quick, reliable method of assessing the acute effects of hyper and microgravity on lower limb perfusion. These methods may be useful to predict healing potential when injuries occur and highlight early warning signs of tissue damage due to poor perfusion. However, additional work to further establish the impact on oxygen transport in the superficial tissues in both acute and sustained microgravity would be beneficial

Innovative Techniques for Managing Dollar Spot in Warm- and Cool-Season Turfgrasses: The Case of UV-B and UV-C Irradiations

The management of Dollar spot, the fungal disease of turfgrasses, is complicated and, today, tends to include new eco-friendly approaches. The aim of this study is to evaluate the effect of UV-B and UV-C lamps against the infection of Clarireedia species in warm- and cool-season turfgrasses. In vitro tests were performed to evaluate the growth of C. jacksonii mycelium on Potato Dextrose Agar, irradiated with UV-B and UV-C at heights of 5 and 15 cm, 5 s per day for three consecutive days. The same treatments, prolonged for seven days, were applied on naturally infected potted Agrostis stolonifera and Cynodon dactylon × C. transvaalensis, for in vivo tests. Disease severity, antioxidant capacity, and pigment content were assessed at the end of the experiment. Only UV-C reduced the growth of C. jacksonii after 48 h at 5 cm (−36%) and 72 h at both distances (−15 and −27%). Agrostis stolonifera showed symptoms, reduced by UV-C at 5 cm, and fungal structures, except in UV-C exposed samples. Total antioxidant capacity increased after UV-B exposure at 5 cm (+10%). No variations in terms of photosynthetic pigments were observed. These results confirm the potential of UV-C lamps for the containment of Dollar spot

Corrigendum: UV-B Pre-treatment Alters Phenolics Response to Monilinia fructicola Infection in a Structure-Dependent Way in Peach Skin

[This corrects the article DOI: 10.3389/fpls.2018.01598.]

Postharvest UV-B exposure drives changes in primary metabolism, phenolic concentration, and volatilome profile in berries of different grape (Vitis vinifera L.) varieties

BACKGROUND The ultraviolet-B (UV-B) radiation can alter grape metabolism during berry development, but little is known on the effect of postharvest UV-B exposure. In this study, we evaluated the effect of postharvest UV-B exposure on berry primary and secondary metabolites in four grapevine varieties (Aleatico, Moscato bianco, Sangiovese, and Vermentino) in order to evaluate the possibility to increase the grape quality and its nutraceutical properties. RESULTS The treatment did not significantly affect the berry primary metabolism in terms of organic acids, carbohydrates, and amino acids profile, regardless of the variety. UV-B exposure reduced the total anthocyanin content, particularly the tri-substituted and di-substituted forms in Aleatico and Sangiovese, respectively. An overall negative effect of UV-B irradiation on the flavonols profile of Aleatico, Moscato bianco, and Vermentino berries was found, whereas it enhanced the quercetin, myricetin and kaempferol concentration in Sangiovese. The free fraction of berry volatile organic compounds increased in UV-B-treated Aleatico and Moscato bianco berries, especially C-13-norisoprenoids and volatile phenols, as well as key monoterpenes, such as the linalool derivatives. However, higher concentrations of glycosylated monoterpenes and C-13-norisoprenoids were measured in Sangiovese and Vermentino berries treated with UV-B. CONCLUSION This study provides new insights on the effect of postharvest UV-B radiation on berry secondary metabolism, highlighting a different modulation between varieties and suggesting the potential use of this technique to increase some nutraceutical and quality characteristics of grape berry