Estudo fitoquímico da fração n-butanólica de Lippia Alba (Mill.) N. E. Br.

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmácia, Florianópolis, 2005.Lippia alba é uma espécie medicinal que ocorre em todas as regiões do Brasil. Caracteriza-se pela sua ampla utilização na medicina popular, sendo utilizada, sobretudo, como tranquilizante. Trata-se de uma espécie que requer estudos científicos sobre isolamento e identificação de seus constituintes. Em estudos anteriores, a fração n-butanólica, obtida por partição do extrato hidroetanólico apresentou efeitos sedativo e anticonvulsivante. Dessa forma, o objetivo deste trabalho foi o estudo desta mesma fração, buscando o isolamento e a identificação de seus constituintes químicos, o acompanhamento sazonal qualitativo destas substâncias e a realização de ensaios farmacológicos (verificação da temperatura corporal e da atividade hipno-sedativa, através da indução com pentobarbital e com éter etílico). Assim, partindo-se de um extrato hidroalcoólico das folhas do material vegetal, seguido de partição com solventes de polaridade crescente, obteve-se a fração n-butanólica. Após purificação das subfrações, foi possível isolar as substâncias LA-1 (verbascosideo), LA-2, LA-3 (ácido 3 , 16 , 23 trihidroxiolean-12-en-28-óico bidesmosídico) e LA-4. Para a substância LA-2 estão sendo aguardados os espectros de RMN para sua elucidação estrutural; para a substância LA-4 deve-se primeiramente purificá-la por CLAE para que seja então igualmente elucidada. Em relação aos testes farmacológicos, não é possível afirmar que a fração n-butanólica apresenta atividade hipno-sedativa, uma vez que prolongou o tempo de sono induzido por barbitúrico (na dose de 300 mg/kg, no tempo de 1 h, v. o.) mas não potencializou o sono induzido por éter, na mesma dose e tempo anteriores; não alterou significativamente a latência do sono, inclusive no grupo diazepam; reduziu a temperatura corporal nas doses de 100 e 300 mg/kg significativamente nos tempos de 1 e 2 h, mas não é possível afirmar que seja devido a um mecanismo de ação central. Dessa forma, constatou-se que L. alba é uma espécie promissora para a obtenção de metabólitos secundários. Os constituintes químicos analisados neste trabalho puderam ser encontrados na espécie em todas as coletas realizadas, não havendo variação sazonal qualitativa. Sugere-se que estudos posteriores realizem pesquisas mais aprofundadas em relação às atividades farmacológicas da fração n-butanólica, bem como de seus constituintes químicos isolados e do infuso. Além disso, devem ser elucidadas as estruturas ainda não identificadas.Lippia alba is a medicinal plant wich is find in all regions of Brazil. This especie is largely used in the folk medicine, especially as a tranquilizer. It needs cientific studies about isolation and identification of its constituents. In previous studies, the n-butanolic fraction, obtained from a hidroalcoolic extract showed sedative and anticonvulsant effects. The objective of this work was the study of the same fraction, searching the isolation and identification from its chemical constituents, the qualitative seasonal accompaniment of this substances and the achievement from pharmacological experiments (verification of the body temperature and sedative activity, through the induction with pentobarbital and ether). Thus, from a hidroalcoolic extract of the leaves from the vegetable material, followed by partition with solvents of increasing polarity, the n-butanolic fraction was obtained. After purification of subfractions, was possible to isolate the substances LA-1 (verbascoside), LA-2, LA-3 (3 , 16 , 23 trihydroxiolean-12-en-28 oic acid bidesmosidic) and LA-4. To the elucidation of the substance LA-2, is necessary wait for the NMR spectrum; to the substance LA-4, is necessary the purification from CLAE to its elucidation. About the pharmacological trials, it is no possible to assure that the n-butanolic fraction shows sedative activity; it increased the barbiturate sleeping time (300 mg/ Kg body wt., 1 h after the treatment v.o.) but not increased the ether sleeping time, at the same previously dose and time; not modified significative the latency of the sleep, including the control group; decreased the body temperature (100 and 300 mg/ Kg wt., 1 and 2 h after the treatment v.o.) but it is no possible to say that is because a central effect. In that way, L. alba is shown as a viable source of potentially active secondary metabolites. The chemical constituents analysed in this work could be find in all assessments, so there is no qualitative seasonal variation. Posterior studies could achieve more researches about the pharmacological activities from the n-butanolic fraction and from its chemical constituents isolated and from the infusion. Furthermore, could elucidate the structures not yet identified

New Perspectives in Phenomenological Psychopathology: Its Use in Psychiatric Treatment

Phenomenological psychopathology is a body of scientific knowledge on which the clinical practice of psychiatry is based since the first decades of the twentieth century, a method to assess the patient's abnormal experiences from their own perspective, and more importantly, a science responsible for delimiting the object of psychiatry. Recently, the frontiers of phenomenological psychopathology have expanded to the productive development of therapeutic strategies that target the whole of existence in their actions. In this article, we present an overview of the current state of this discipline, summing up some of its key concepts, and highlighting its importance to clinical psychiatry today. Phenomenological psychopathology understands mental disorders as modifications of the main dimensions of the life-world: lived time, lived space, lived body, intersubjectivity, and selfhood. Psychopathological symptoms are the expression of a dialectical modification of the proportions of certain domains of the life-world or of the lived experience. The far-reaching relevance of the concepts of proportion and dialectics for the clinical agenda is explored. The article presents two contemporary models for clinical practice based on phenomenological psychopathology: Dialectical-proportional oriented approach and Person-centered dialectic approach (P.H.D. method). The main characteristics of these approaches are considered, as well as the new perspectives they bring to the challenges of psychiatric care in the twentieth-first century

Studies on the Cobalt Deficiency in Ruminants (III) : Effects of Thiamine, Glucose and Cobalamin Injection on the Metabolism of Cobalt-deficient Sheep

International audienceN-terminal acetylation is a common protein modification in eukaryotes associated with numerous cellular processes. Inherited mutations in NAA10, encoding the catalytic subunit of the major N-terminal acetylation complex NatA have been associated with diverse, syndromic X-linked recessive disorders, whereas de novo missense mutations have been reported in one male and one female individual with severe intellectual disability but otherwise unspecific phenotypes. Thus, the full genetic and clinical spectrum of NAA10 deficiency is yet to be delineated. We identified three different novel and one known missense mutation in NAA10, de novo in 11 females, and due to maternal germ line mosaicism in another girl and her more severely affected and deceased brother. In vitro enzymatic assays for the novel, recurrent mutations p.(Arg83Cys) and p.(Phe128Leu) revealed reduced catalytic activity. X-inactivation was random in five females. The core phenotype of X-linked NAA10-related N-terminal-acetyltransferase deficiency in both males and females includes developmental delay, severe intellectual disability, postnatal growth failure with severe microcephaly, and skeletal or cardiac anomalies. Genotype–phenotype correlations within and between both genders are complex and may include various factors such as location and nature of mutations, enzymatic stability and activity, and X-inactivation in females

Tricks and treats: designing technology to support mobility assistance dogs

Assistance dogs are a key intervention to support the autonomy of people with tetraplegia. Previous research on assistive technologies have investigated ways to, ultimately, replace their labour using technology, for instance through the design of smart home environments. However, both the disability studies literature and our interviews suggest there is an immediate need to support these relationships, both in terms of training and bonding. Through a case study of an accessible dog treats dispenser, we investigate a technological intervention responding to these needs, detailing an appropriate design methodology and contributing insights into user requirements and preferences

NPM1 directs PIDDosome-dependent caspase-2 activation in the nucleolus

The PIDDosome (PIDD–RAIDD–caspase-2 complex) is considered to be the primary signaling platform for caspase-2 activation in response to genotoxic stress. Yet studies of PIDD-deficient mice show that caspase-2 activation can proceed in the absence of PIDD. Here we show that DNA damage induces the assembly of at least two distinct activation platforms for caspase-2: a cytoplasmic platform that is RAIDD dependent but PIDD independent, and a nucleolar platform that requires both PIDD and RAIDD. Furthermore, the nucleolar phosphoprotein nucleophosmin (NPM1) acts as a scaffold for PIDD and is essential for PIDDosome assembly in the nucleolus after DNA damage. Inhibition of NPM1 impairs caspase-2 processing, apoptosis, and caspase-2–dependent inhibition of cell growth, demonstrating that the NPM1-dependent nucleolar PIDDosome is a key initiator of the caspase-2 activation cascade. Thus we have identified the nucleolus as a novel site for caspase-2 activation and function

Slégami Open Access - Manuale d'uso per ricercatori

Il seguente documento nasce nell’ambito delle attività svolte dal Gruppo di Lavoro (GdL) APRE dedicato al tema dell’Open Science e si sviluppa come un manuale d’uso per i ricercatori, con specifico riguardo all’Open Access e all’Open Data. La sua redazione ha coinvolto attivamente tutti i membri del GdL, i cui membri sono rappresentanti delle biblioteche e degli uffici di supporto alla ricerca di diverse università e centri di ricerca italiani (è possibile consultare la lista dei partecipanti nell’ultima pagina di questo documento). Il lavoro è un aggiornamento del manuale originariamente pubblicato nel 2019 e la cui prima edizione era il risultato di un lavoro svolto in 3 fasi: 1) un’iniziale raccolta delle domande più comuni poste dai ricercatori presso le strutture di supporto (siano esse biblioteche o uffici di supporto alla ricerca) degli enti partecipanti in materia di Open Access e Open Data; 2) una fase di consolidamento e classificazione delle domande raccolte in 6 categorie; 3) un’ultima fase di redazione, da parte di alcuni membri del GdL, delle risposte alle domande poste e successivamente emendate a più riprese dall’intero gruppo. Nel 2021 il GdL si è riunito nuovamente per lavorare ad un aggiornamento del manuale in ottica Horizon Europe. Seguendo lo stesso schema di lavoro in 3 fasi (raccolta, classificazione ed elaborazione), il gruppo ha identificato 76 domande aggiuntive rispetto al documento originale, le quali a loro volta sono state successivamente raggruppate e classificate in 10 categorie

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features

Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation