Impulse Response Analysis at the Zero Lower Bound

We study whether the response of the economy to structural shocks changes at the zero lower bound. Monte Carlo evidence suggests that VARs have a limited ability to detect changes in impulse response functions at the ZLB compared to the standard environment with positive interest rates. This issue is confounded given the short sample lengths that characterize ZLB episodes. This is especially the case for timevarying parameter VARs, whose estimates are two-sided, and therefore tend to smooth changes across regimes. In contrast, fixed-coefficient VARs estimated by sub-sample exhibit greater power. Pooled estimates from panel VARs for six countries based on (long-run and) sign restrictions detect in several instances changes in the IRFs. This evidence is, however, weaker than it appears. Based on (long-run and) sign restrictions we find that prior and posterior IRFs are often close, so that the concern raised by Baumeister and Hamilton (2015) appears to be relevant. Evidence from a multivariate permanent-transitory decomposition of GDP shocks is markedly sharper. It points towards material changes in the IRFs: at the ZLB the IRFs of GDP and unemployment exhibit more inertia, the response of prices is flatter, and the responses of interest rates are weaker

Engineered Sleeping Beauty Transposon as Efficient System to Optimize Chimp Adenoviral Production

Sleeping Beauty (SB) is the first DNA transposon employed for efficient transposition in vertebrate cells, opening new applications for genetic engineering and gene therapies. A transposon-based gene delivery system holds the favourable features of non-viral vectors and an attractive safety profile. Here, we employed SB to engineer HEK293 cells for optimizing the production of a chimpanzee Adenovector (chAd) belonging to the Human Mastadenovirus C species. To date, chAd vectors are employed in several clinical settings for infectious diseases, last but not least COVID-19. A robust, efficient and quick viral vector production could advance the clinical application of chAd vectors. To this aim, we firstly swapped the hAd5 E1 with chAd-C E1 gene by using the CRISPR/Cas9 system. We demonstrated that in the absence of human Ad5 E1, chimp Ad-C E1 gene did not support HEK293 survival. To improve chAd-C vector production, we engineered HEK293 cells to stably express the chAd-C precursor terminal protein (ch.pTP), which plays a crucial role in chimpanzee Adenoviral DNA replication. The results indicate that exogenous ch.pTP expression significantly ameliorate the packaging and amplification of recombinant chAd-C vectors thus, the engineered HEK293ch.pTP cells could represent a superior packaging cell line for the production of these vectors

Subcutaneous adipose tissue classification

The developments in the technologies based on the use of autologous adipose tissue attracted attention to minor depots as possible sampling areas. Some of those depots have never been studied in detail. The present study was performed on subcutaneous adipose depots sampled in different areas with the aim of explaining their morphology, particularly as far as regards stem niches. The results demonstrated that three different types of white adipose tissue (WAT) can be differentiated on the basis of structural and ultrastructural features: deposit WAT (dWAT), structural WAT (sWAT) and fibrous WAT (fWAT). dWAT can be found essentially in large fatty depots in the abdominal area (periumbilical). In the dWAT, cells are tightly packed and linked by a weak net of isolated collagen fibers. Collagenic components are very poor, cells are large and few blood vessels are present. The deep portion appears more fibrous then the superficial one. The microcirculation is formed by thin walled capillaries with rare stem niches. Reinforcement pericyte elements are rarely evident. The sWAT is more stromal; it is located in some areas in the limbs and in the hips. The stroma is fairly well represented, with a good vascularity and adequate staminality. Cells are wrapped by a basket of collagen fibers. The fatty depots of the knees and of the trochanteric areas have quite loose meshes. The fWAT has a noteworthy fibrous component and can be found in areas where a severe mechanic stress occurs. Adipocytes have an individual thick fibrous shell. In conclusion, the present study demonstrates evident differences among subcutaneous WAT deposits, thus suggesting that in regenerative procedures based on autologous adipose tissues the sampling area should not be randomly chosen, but it should be oriented by evidence based evaluations. The structural peculiarities of the sWAT, and particularly of its microcirculation, suggest that it could represent a privileged source for regenerative procedures based on autologous adipose tissues

Spad index for diagnosis of nitrogen status in 'Esmeralda' peach.

O objetivo do presente trabalho foi avaliar a viabilidade técnica do índice SPAD no diagnóstico do estado de N em pessegueiros cv. Esmeralda. O experimento, com cinco níveis de N aplicado no solo (0; 40; 80; 120 e 160 kg ha-1 de N na forma de ureia), foi conduzido a campo, em delineamento experimental de blocos ao acaso, com quatro repetições. Durante os anos de 2014, 2015, 2016 e 2017, realizaram-se leituras com clorofilômetro, modelo Minolta SPAD-502, na parte mediana da folha, em 40 folhas por parcela. A determinação do teor foliar de N foi realizada em Analisador ElementarCHN-S. O índice SPAD e o teor de N nas folhas aumentaram de forma linear, de acordo com o aumento das doses de N aplicadas no solo. Houve efeito das doses de N aplicadas no solo sobre o índice SPAD, e os teores foliares de N apresentaram correlação linear positiva com as leituras SPAD (0.652; 0.756; 0.762 e 0.767, p<0.05). O índice SPAD pode ser utilizado no diagnóstico nutricional de N em pessegueiro, quando as leituras são realizadas entre a 13a e a 15a semana após a plena floração. Na faixa compreendida entre 39 e 49, o índice SPAD indica que o N foliar está compreendido na classe ?normal? (33 ? 45 g kg-1) de interpretação agronômica, para os Estados do Rio Grande do Sul e de Santa Catarina, Brasil

Allele-specific editing ameliorates dominant retinitis pigmentosa in a transgenic mouse model

Retinitis pigmentosa (RP) is a group of progressive retinal degenerations of mostly monogenic inheritance, which cause blindness in about 1:3,500 individuals worldwide. Heterozygous variants in the rhodopsin (RHO) gene are the most common cause of autosomal dominant RP (adRP). Among these, missense variants at C-terminal proline 347, such as p.Pro347Ser, cause severe adRP recurrently in European affected individuals. Here, for the first time, we use CRISPR/Cas9 to selectively target the p.Pro347Ser variant while preserving the wild-type RHO allele in vitro and in a mouse model of adRP. Detailed in vitro, genomic, and biochemical characterization of the rhodopsin C-terminal editing demonstrates a safe downregulation of p.Pro347Ser expression leading to partial recovery of photoreceptor function in a transgenic mouse model treated with adeno-associated viral vectors. This study supports the safety and efficacy of CRISPR/Cas9-mediated allele-specific editing and paves the way for a permanent and precise correction of heterozygous variants in dominantly inherited retinal diseases

The trochanteric fat pad

Technological developments based on the use of autologous white adipose tissue (WAT) attracted attention to minor fat depots as possible sources of adipose tissue. In plastic surgery, the trochanteric fatty pad is one of the most used WAT depots for its location and organoleptic characteristics that make it particularly suitable for reconstructive procedures. Despite its wide use in clinic, the structure of this depot has never been studied in detail and it is not known if structural differences exist among trochanteric fat and other subcutaneous WAT depots. The present study was performed on trochanteric fat pad with the aim to clarify the morphology of its adipocytes, stroma and microcirculation, with particular reference to the stem niches. Histological and ultrastructural studies showed that the main peculiar feature of the trochanteric fat concerns its stromal component, which appears less dense than in the other subcutaneous WATs studied. The intra-parenchymal collagen stroma is poor and the extracellular compartment shows large spaces, filled with electron-light material, in which isolated collagen bundles are present. The adipocytes are wrapped in weak and easily detachable collagen baskets. These connective sheaths are very thin compared to the sheaths in other subcutaneous WAT depots. The capillaries are covered by large, long and thin elements surrounded by an external lamina; these perivascular cells are poor in organelles and mainly contain poly-ribosomes. In conclusion, when compared to other WAT deposits, the trochanteric fatty pad shows structural peculiarities in its stroma and microcirculation suggesting a high regenerative potential. Resistance, dissociability, microvascular weft and high regenerative potential make the trochanteric fatty pad a privileged source for harvesting in autologous WAT-based regenerative procedures

Nitrogen fertilization associated with cold storage and its impacts on the maintenance of peach quality.

Nitrogen, which is considered the most important nutrient for peach trees, may interfere in both quantitative production characteristics and quality of fruits. This study aimed at evaluating the effect of the combination of doses of N fertilization and different periods of cold storage on physico-chemical and phytochemical characteristics of peaches in post-harvest. The experiment had a randomized complete block design in a 4x3 factorial scheme, i. e., four doses of fertilization (0, 60, 120 and 180 Kg N ha-1) and three periods of storage (on the harvest day, on both the 15th and the 30th storage days at 1±1ºC, each followed by a day of simulated commercialization at 20±1ºC). The following aspects were evaluated in fruits yielded by peach trees of the genotype Cascata 1067: fruit color, soluble solid content, titratable acidity, pulp firmness, mass loss, total phenolic compounds and antioxidant activity. Different periods of cold storage and doses of N fertilization were found to affect epidermis luminosity, pulp firmness and titratable acidity of fruits. Peaches may be stored at low temperatures for 15+1 days. After that, loss of fruit firmness increases. N fertilization affects neither the soluble solid content nor the epidermis color of peaches, but both parameters are influenced by storage. Values of phenolic compounds and antioxidant activity decrease when there is N increment in the soil and when longer storage is carried out. Results suggest that peach composition may be affected by cultural practices, such as N fertilization, in harvest and after storage

Digital dermoscopic changes during follow-up of de-novo and nevus-associated melanoma: a cohort study

Background: Nevus-associated melanoma (NAM) has been regarded as a distinct biological entity from de-novo melanoma (DNM); however, static dermoscopy often fails in differentiating these entities. Digital dermoscopic monitoring allows to identify dynamic changes occurring during follow-up; this may improve diagnostic accuracy and potentially our knowledge on NAM biology. We aimed to define main independent factors associated with NAM diagnosis and those influencing follow-up time in a population of melanomas excised at follow-up. Methods: A cohort of melanomas excised at follow-up was retrospectively and consecutively selected. NAMs and DNMs were compared according to baseline features and main dermoscopic changes occurring during follow-up. Univariate and multivariable logistic and Cox's regression analysis were performed to respectively define factors associated with NAM diagnosis and those influencing the risk for excision. Results: Eighty-six melanomas were enrolled, of which 21 (24.4%) were nevus-associated. During follow-up NAMs mainly underwent atypical network modifications (47.6%), followed by inverse network (28.6%) and dermoscopic island (23.8%) worsening or appearance. DNMs were also mainly characterized by atypical network modifications (47.7%), however, a significant proportion of cases underwent irregular pigmentation/dots/globules or regression changes (29.2%), which were rarely seen among NAMs. Furthermore, both multivariable logistic and Cox's regression analysis demonstrated a significant association between NAM and a longer follow-up. Conclusions: We demonstrated that among melanomas excised at follow-up, different patterns of dermoscopic changes may be found between NAMs and DNMs. This finding, together with the association of NAM with a longer follow-up time, supports the hypothesis of different biological behavior of these two entities

Dark chocolate modulates platelet function with a mechanism mediated by flavan-3-ol metabolites

Cocoa is a rich source bioactive compounds, i.e., flavan-3-ols, and its consumption has been associated with several beneficial effects, such as the positive modulation of the hemostasis targeted by the platelet function. However, these phenolic compounds have a very low bioavailability and extensively undergo phase I and II metabolism, with the appearing into the bloodstream of (epi) catechin conjugates and phenyl-g-valerolactones and their conjugates, at different times. The aims of this study were to explore the effect of dark chocolate on platelet function and to investigate the relationship between this interplay and flavan-3-ol derived metabolites. Eighteen healthy male volunteers ingested 50 g of 90% cocoa chocolate within 5 minutes. Blood samples were collected immediately before chocolate ingestion (T0) and 4 hours afterwards (T1). Platelet function analyzer (PFA)-100 closure time was assessed using collagen/adenosine-50-diphosphate (COL/ADP) and collagen/epinephrine (COL/EPI) cartridges. Plasma flavan-3-ol metabolites were identified and quantified by means of liquid chromatography coupled to a triple quadrupole mass spectrometer (UHPLC-ESI-MS/MS). Results evidenced a significant increase of COL/ADP-induced PFA-100 closure time, but not COL/EPI, 4 hours after ingestion of dark chocolate. Total plasma structurally-related (epi)catechin metabolite (SREM) concentration significantly increased at T1, together with 4 out of the 6 detected metabolites. Total phenyl-g-valerolactone concentrations remained unchanged. Spearman correlations evidenced a strong correlation between COL/ADP closure time and SREMs, mainly led by (epi)catechin-sulfate isomers. These data confirm that the potential beneficial effect of dark chocolate on primary hemostasis may be mediated by flavan-3-ol circulating metabolites

Zoneamento das condições atuais e futuras de frio para o controle natural da endodormência em clones de Moscato Branco e cvs Vitis labrusca no sul do Brasil.

Como uma planta de clima temperado, a videira necessita de um acúmulo de horas frio (HF, T<7,2°C) para superar o estado de endodormência e ter uma brotação regular, o que é variável entre genótipos. Confrontando essa demanda com as previsões de mudanças climáticas e diminuição de frio, o presente trabalho objetivou contabilizar e delimitar o zoneamento atual e futuro para o cultivo de diferentes clones de Moscato Branco (Vitis vinifera) e cultivares Vitis labrusca