A expansão da justiça penal negociada no Brasil: uma análise comparativa entre o acordo de não persecução penal e a plea bargaining norte-americana

This article aims to analyze the expansion of Brazil’s negotiated justice in criminal matters, focusing on the study of the new non-criminal prosecution agreement, introduced in the Brazilian Criminal Procedure Code through the article 28-A. In a comparative perspective, in order to examine the American Plea Bargaining’s influence in this phenomenon, the investigation shifts to the adversarial system, its origin and characteristics. Therefore, it is possible to verify the incompatibility of the introduction of consensual mechanisms in inquisitorial originated countries, due to the substantial differences between their procedural systems. In spite of this, there’s a large movement towards negociated justice institutes by Civil Law countries, as verified from the Italian (patteggiamento) and German (absprachen) experiences. Brazil, over the past few decades, has followed the same logic. Regarding the recent introduction of the institute, the non-criminal prosecution agreement, despite its huge differences compared to the American Plea Bargaining, it seems reprehensible considering the incompatibility with the brasilian accusatory system principles. This criticisms represents the challenges that must be faced by Law operators to adapt the new institute considering the scope of constitutional guarantees.O presente trabalho pretende analisar a expansão da justiça penal negociada no Brasil, dando ênfase ao estudo do novo acordo de não persecução penal, introduzido no Código de Processo Penal Brasileiro por meio do artigo 28-A. Adotando-se uma perspectiva comparada, a fim de examinar a influência que o modelo norte-americano da plea bargaining exerceu nesse fenômeno, volta-se à compreensão do sistema adversarial, sua origem e características. A partir desse estudo, verifica-se a incompatibilidade da introdução de mecanismos consensuais penais nos países de matriz inquisitorial, em razão das diferenças basilares entre os referidos sistemas processuais. Apesar disso, observa-se o grande movimento de adoção de institutos negociais pelos países de Civil Law, como se vê das experiências italiana (patteggiamento) e alemã (absprachen). O Brasil, ao longo das últimas décadas, tem seguido a mesma tendência. Com relação ao instituto mais recentemente adotado, o acordo de não persecução penal, embora distinto do modelo norte-americano em diversos aspectos, não é isento de críticas, tendo em vista a sua incompatibilidade com os princípios previstos pelo sistema acusatório, adotado por esse país. Tais críticas representam os desafios que deverão ser enfrentados pelos operadores do Direito para adequação do novo instituto às garantias constitucionais

Advertiser’s Digital Maturity: a Multi-Case Study in Brazilian Companies

The present article deliberates the present state of Brazil’s advertiser’s digital maturity through a descriptive exploratory qualitative study on three cases of brazilian companies having as a basis the Digital Maturity Model developed by the Boston Consulting Group in 2018. The interviews were shaped with the goal of understanding the conditioning factors, facilitators and obstacles faced by brazilian companies on achieving higher stages of maturity. The biggest conditioning facts observer were company’s: operating sector, public, sales cycle, business model and seniority. As facilitators, an organizational structure that reflects structures and prioritized marketing processes; having the consumer journey mapped from the perspective of both the customer and the sales team; and the constant update on Digital Marketing news and best practices by the company and its professionals. The biggest obstacles observed were the lack of technology to fully integrate online and offline audiences; the fact that digital channels are not yet mass channels; the low qualification of marketers due to market dynamics; and, finally, the lack of high management\u27s understanding of digital metrics and therefore pressure for results that do not reflect the actual impact of campaigns on the business

Apically extruded debris using passive ultrasonic irrigation associated with different root canal irrigants

The present study evaluated the amount of apically extruded debris after chemo-mechanical preparation (CMP) associated with passive ultrasonic irrigation (PUI) using four different root canal irrigants, namely, 6% sodium hypochlorite (NaOCl), 2% chlorhexidine gel + saline solution (2% CHXg+SS), 2% chlorhexidine solution (2% CHXs) and SS alone. Sixty mandibular premolars with single straight root canals were selected and randomly assigned into 4 groups (n=15) according to the root canal irrigant used as follows: G1 (PUI + NaOCl), G2 (PUI + CHXg+SS), G3 (PUI+CHXs) and G4 (PUI+SS). Reciproc® R25 files (25/.08) were used during CMP and the debris extruded from each tooth were collected in pre-weighted Eppendorf tubes and dried. The average weight of debris was assessed by using an analytical microbalance. Data were statistically analysed by using ANOVA and post-hoc Tukey’s test (a=0.05). Debris extrusion was observed in all groups, irrespective of the root canal irrigating, with 2% CHXg + SS being associated with lower debris extrusion compared to other irrigants (p<0.05). No significant differences were observed between 6% NaOCl, 2% CHXs and SS. In conclusion, passive ultrasonic irrigation did not completely prevent apically extrusion of debris. PUI performed with 2% chlorhexidine gel + saline solution significantly minimized debris extrusion compared to 6% sodium hypochlorite, chlorhexidine solution and saline solution304363367CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP308162/2014-50012015/23.479-5; 2017/25242-8O presente estudo avaliou a quantidade de debris extruídos apicalmente após o preparo químico-mecânico (PQM) associado à irrigação ultrassônica passiva (IUP) em associação com quatro diferentes irrigantes - hipoclorito de sódio 6% (NaOCl), clorexidina gel 2% + solução salina (CLXg 2% + SS), solução de clorexidina 2% (CLXs 2%) e SS. Sessenta pré-molares inferiores com canais radiculares únicos e retos foram selecionados e aleatoriamente distribuídos em 4 grupos (n=15) de acordo com o irrigante utilizado: G1 (IUP + NaOCl), G2 (IUP + CLXg + SS), G3 (IUP + CLXs) e G4 (IUP + SS). Limas Reciproc® R25 (25/.08) foram utilizadas durante o PQM e os debris extruídos de cada dente foram coletados em tubos Eppendorf pré-pesados e secos. O peso médio de debris foi avaliado através de microbalança analítica, e os dados foram analisados estatisticamente utilizando ANOVA e teste de Tukey post hoc (a=0.05). Extrusão de debris foi observada em todos os grupos, independente do irrigante. CHXg 2% + SS foram associados a menor extrusão de debris comparado aos demais irrigantes (p<0.05). Não foram observadas diferenças estatisticamente significativas entre NaOCl 6%, CLXs 2% e SS. Concluindo, irrigação ultrassônica passiva não preveniu completamente a extrusão apical de debris, entretanto, IUP realizada com CLXg 2% + SS minimiza significativamente a extrusão de debris comparado ao NaOCl 6%, CLXs 2% e S

A complex pheotype in a girl with a novel heterozygous missense variant (p.Ile56Phe) of the GNAS gene

Background: GNAS is a complex gene that encodes Gsα, a signaling protein that triggers a complex network of pathways. Heterozygous inactivating mutations in Gsα-coding GNAS exons cause hormonal resistance; on the contrary, activating mutations in Gsα result in constitutive cAMP stimulation. Recent research has described a clinical condition characterized by both gain and loss of Gsα function, due to a heterozygous de novo variant of the maternal GNAS allele. Patients and methods: We describe a girl with a complex combination of clinical signs and a new heterozygous GNAS variant. For the molecular analysis of GNAS gene, DNA samples of the proband and her parents were extracted from their peripheral blood samples. In silico analysis was performed to predict the possible in vivo effect of the detected novel genetic variant. The activity of Gsα protein was in vitro analyzed from samples of erythrocyte membranes, recovered from heparinized blood samples. Results: We found a new heterozygous missense c.166A &gt; T-(p.Ile56Phe) GNAS variant in exon 2, inherited from the mother that determined a reduced activity of 50% of Gsα protein function. The analysis of her parents showed a 20-25% reduction in Gsα protein activity in the mother and a normal function in the father. Clinically our patient presented a multisystemic disorder characterized by hyponatremia compatible with a nephrogenic syndrome of inappropriate antidiuresis, subclinical hyperthyroidism, subclinical hypercortisolism, precocious thelarche and pubarche and congenital bone abnormalities. Conclusions: This is the first time that the new variant c.166A &gt; T (p.Ile56Phe) on exon 2 of GNAS gene, originated on maternal allele, has been described as probable cause of a multisystemic disorder. Although the mutation is associated with a reduced activity of the function of Gsα protein, this unusual phenotype on the contrary suggests a mild functional gain

Dimerization of GPCRs:Novel insight into the role of FLNA and SSAs regulating SST₂ and SST₅ homo- and hetero-dimer formation

The process of GPCR dimerization can have profound effects on GPCR activation, signaling, and intracellular trafficking. Somatostatin receptors (SSTs) are class A GPCRs abundantly expressed in pituitary tumors where they represent the main pharmacological targets of somatostatin analogs (SSAs), thanks to their antisecretory and antiproliferative actions. The cytoskeletal protein filamin A (FLNA) directly interacts with both somatostatin receptor type 2 (SST2) and 5 (SST5) and regulates their expression and signaling in pituitary tumoral cells. So far, the existence and physiological relevance of SSTs homo- and hetero-dimerization in the pituitary have not been explored. Moreover, whether octreotide or pasireotide may play modulatory effects and whether FLNA may participate to this level of receptor organization have remained elusive. Here, we used a proximity ligation assay (PLA)-based approach for the in situ visualization and quantification of SST2/SST5 dimerization in rat GH3 as well as in human melanoma cells either expressing (A7) or lacking (M2) FLNA. First, we observed the formation of endogenous SST5 homo-dimers in GH3, A7, and M2 cells. Using the PLA approach combined with epitope tagging, we detected homo-dimers of human SST2 in GH3, A7, and M2 cells transiently co-expressing HA- and SNAP-tagged SST2. SST2 and SST5 can also form endogenous hetero-dimers in these cells. Interestingly, FLNA absence reduced the basal number of hetero-dimers (-36.8 ± 6.3% reduction of PLA events in M2, P &lt; 0.05 vs. A7), and octreotide but not pasireotide promoted hetero-dimerization in both A7 and M2 (+20.0 ± 11.8% and +44.1 ± 16.3% increase of PLA events in A7 and M2, respectively, P &lt; 0.05 vs. basal). Finally, immunofluorescence data showed that SST2 and SST5 recruitment at the plasma membrane and internalization are similarly induced by octreotide and pasireotide in GH3 and A7 cells. On the contrary, in M2 cells, octreotide failed to internalize both receptors whereas pasireotide promoted robust receptor internalization at shorter times than in A7 cells. In conclusion, we demonstrated that in GH3 cells SST2 and SST5 can form both homo- and hetero-dimers and that FLNA plays a role in the formation of SST2/SST5 hetero-dimers. Moreover, we showed that FLNA regulatesSST2 and SST5 intracellular trafficking induced by octreotide and pasireotide. </p

Corpos e existências: vidas não passíveis de luto

O objetivo deste artigo é refletir sobre a relação entre políticas sociais e performances dos corpos em termos de governo das vidas. O que interessa a esta discussão é percorrer um campo de problematização dessa articulação – políticas sociais e corpos – a partir da emergência da atual crise sanitária, causada pela pandemia de COVID-19. Essa problematização focaliza os efeitos sociais nas relações de governo dos corpos dentro de uma racionalidade de colonialidade e de racismo, ou seja, queremos pensar certas linhas de governo das vidas que se intensificam em formas de abandono, tornando-as não passíveis de luto. Para tanto, tomaremos duas performances de corpos em nossa atualidade – mulheres em situação de violência e usuários de drogas em situação de rua –, na medida em que ambas indicam mecanismos distintos de regulação de corpos e formas de abandono das vidas

The transcription factor NF-Y participates to stem cell fate decision and regeneration in adult skeletal muscle

Satellite cells represent myogenic stem cells that allow the homeostasis and repair of adult skeletal muscle. Here the authors report that the transcription factor NF-Y is expressed in satellite cells and is important for their maintenance and proper myogenic differentiation

Filamin A organizes γ‑aminobutyric acid type B receptors at the plasma membrane

The γ-aminobutyric acid type B (GABA(B)) receptor is a prototypical family C G protein-coupled receptor (GPCR) that plays a key role in the regulation of synaptic transmission. Although growing evidence suggests that GPCR signaling in neurons might be highly organized in time and space, limited information is available about the mechanisms controlling the nanoscale organization of GABA(B) receptors and other GPCRs on the neuronal plasma membrane. Using a combination of biochemical assays in vitro, single-particle tracking, and super-resolution microscopy, we provide evidence that the spatial organization and diffusion of GABA(B) receptors on the plasma membrane are governed by dynamic interactions with filamin A, which tethers the receptors to sub-cortical actin filaments. We further show that GABA(B) receptors are located together with filamin A in small nanodomains in hippocampal neurons. These interactions are mediated by the first intracellular loop of the GABA(B1) subunit and modulate the kinetics of Gα(i) protein activation in response to GABA stimulation

Proliferation of Transformed Somatotroph Cells Related to Low or Absent Expression of Protein Kinase A Regulatory Subunit 1A Protein

Abstract The two regulatory subunits (R1 and R2) of protein kinase A (PKA) are differentially expressed in cancer cell lines and exert diverse roles in growth control. Recently, mutations of the PKA regulatory subunit 1A gene (PRKAR1A) have been identified in patients with Carney complex. The aim of this study was to evaluate the expression of the PKA regulatory subunits R1A, R2A, and R2B in a series of 30 pituitary adenomas and the effects of subunit activation on cell proliferation. In these tumors, neither mutation of PRKAR1A nor loss of heterozygosity was identified. By real-time PCR, mRNA of the three subunits was detected in all of the tumors, R1A being the most represented in the majority of samples. By contrast, immunohistochemistry documented low or absent R1A levels in all tumors, whereas R2A and R2B were highly expressed, thus resulting in an unbalanced R1/R2 ratio. The low levels of R1A were, at least in part, due to proteasome-mediated degradation. The effect of the R1/R2 ratio on proliferation was assessed in GH3 cells, which showed a similar unbalanced pattern of R subunits expression, and in growth hormone-secreting adenomas. The R2-selective cAMP analog 8-Cl cAMP and R1A RNA silencing, stimulated cell proliferation and increased Cyclin D1 expression, respectively, in human and rat adenomatous somatotrophs. These data show that a low R1/R2 ratio promoted proliferation of transformed somatotrophs and are consistent with the Carney complex model in which R1A inactivating mutations further unbalance this ratio in favor of R2 subunits. These results suggest that low expression of R1A protein may favor cAMP-dependent proliferation of transformed somatotrophs