Atomistic Origins of Resurrection of Aged Acetylcholinesterase by Quinone Methide Precursors.

Nerve agents are organophosphates (OPs) that act as potent inhibitors of acetylcholinesterase (AChE), the enzyme responsible for the hydrolysis of acetylcholine. After inhibition, a dealkylation reaction of the phosphorylated serine, known as the aging of AChE, can occur. When aged, reactivators of OP-inhibited AChE are no longer effective. Therefore, the realkylation of aged AChE may offer a pathway to reverse AChE aging. In this study, molecular modeling was conducted to propose new ligands as realkylators of aged AChE. We applied a methodology involving docking and quantum mechanics/molecular mechanics (QM/MM) calculations to evaluate the resurrection kinetic constants and ligand interactions with OP-aged AChE, comparing them to data found in the literature. The results obtained confirm that this method is suitable for predicting kinetic and thermodynamic parameters of ligands, which can be useful in the design and selection of new and more effective ligands for AChE realkylation.

Modulation of autophagy by an innovative phytocosmetic preparation (Myrothamnus flabelifolia and Coffea arabica) in human fibroblasts and its effects in a clinical randomized placebo-controlled trial.

BACKGROUND: Autophagy is a natural and evolutionary mechanism that reduces cell toxic components and reutilizes metabolites to provide energy and renew cell function, which is linked to a wide range of age-related diseases, including those that affect the skin. Positive modulation of autophagy is useful to treat skin disorders and new active herbal products are potential candidates as autophagy modulators. AIMS: The present study aimed to evaluate the effects of a phytocosmetic formulation containing Myrothamnus flabellifolia leaf and Coffea arabica seed plant extracts (MflCas) on the ubiquitin-proteasome and autophagy markers in human dermal fibroblasts, and investigate its topical skin effects in a randomized, simple-blind, and placebo-controlled trial. METHODS: Human dermal fibroblasts were used to determine proteasome activity, protein carbonylation, LC3B protein, and lipofuscin production by luminescence and immune-enzymatic assays, and to determinate gene expression of autophagy biomarkers (Atg5, Atg7, EI24, EIF2A, Park2, foxo1, and mTOR) by RT-PCR. A clinical trial was conducted to evaluate the effects of MflCas on the hand, face, and forearms skin features after treatment by 56 days. RESULTS: Topical treatment with MflCas improved several skin features of volunteers, mainly skin aging and pigmentation signals. On the hand skin, MflCas 2% after 56 days of treatment, reduced the spots length (30.8%), skin contrast (42.2%), and increased skin homogeneity (63.2%) and skin lightening effect (1.4%). On the face skin, topical treatment after 56 days reduced the spots length (21.5%), wrinkles area (8.1%), and wrinkles volume (5.6%) with an increment in face skin homogeneity (59.5%). These effects were related to the ability of MflCas to reduce proteasome activity protein carbonylation, and lipofuscin level, increase LC3B production, downregulate Atg7 and mTOR genes, and upregulate Park2 gene expressions. CONCLUSIONS: The phytocosmetic preparation containing Myrothamnus flabellifolia leaf and Coffea arabica seed modulated ubiquitin-proteasome and autophagy process, representing an innovative and safe herbal preparation to improve skin features, mainly acting as skin anti-aging and lightening agent.

Rapid Evolution of Seed Dormancy During Sunflower De-Domestication.

Hybridization between crops and their wild relatives may promote the evolution of de-domesticated (feral) weeds. Wild sunflower (Helianthus annuus L.) is typically found in ruderal environments, but crop-wild hybridization may facilitate the evolution of weedy populations. Using 1 crop-specific mitochondrial marker (CMS-PET1) and 14 nuclear SSR markers, we studied the origin and genetic diversity of a recently discovered weedy population of sunflower (named BRW). Then, using a resurrection approach, we tested for rapid evolution of weedy traits (seed dormancy, herbicide resistance, and competitive ability) by sampling weedy and wild populations 10 years apart (2007 and 2017). All the weedy plants present the CMS-PET1 cytotype, confirming their feral origin. At the nuclear markers, BRW showed higher genetic diversity than the cultivated lines and low differentiation with one wild population, suggesting that wild hybridization increased their genetic diversity. We found support for rapid evolution towards higher seed dormancy, but not for higher competitive ability or herbicide resistance. Our results highlight the importance of seed dormancy during the earliest stages of adaptation and show that crop-wild hybrids can evolve quickly in agricultural environments.

A morte e a ressurreição do Messias: A Sombra, o Mal e o Anticristo. Um estudo da função ética, pela Psicologia Simbólica Junguiana / The death and resurrection of the Messiah: The Shadow, the Evil and the Antichrist. A study of the ethical function, by Jungian Symbolic Psychology / La muerte y la resurrección del Mesías: La Sombra, el Mal y el Anticristo. Un estudio de la función ética, por la Psicología Simbólica Junguiana

O artigo conceitua o Arquétipo da Sombra como o Arquétipo do Mal na Psicologia Simbólica Junguiana e busca integrá-lo como expressão do Arquétipo Central, ao lado do Arquétipo do Bem. A interpretação de Jung da limitação da imagem de Jeovah na relação com Job é aqui continuada com o reconhecimento do sadismo do Deus patriarcal, que necessita do filicídio sacrificial para transformar-se no Deus da compaixão e do entendimento, pois só assim se tornará a Trindade e expressará o Arquétipo da Alteridade. Em conclusão, o autor segue Jung na interpretação do Apoccomo a Sombra do Novo Testamento e chama a atenção para o texto ser escrito em nome de Jesus, o que sugere a integração do símbolo do Anticristo no mito, como a Sombra de Jesus. ■

The article conceives the archetype of shadow as the archetype of evil in Jungian Symbolic Psychology and tries to interpret it as an expression of the central archetype (Self) side by side with the archetype of good. Jung's interpretation of Jehovah's limitation in the relationship with Job is followed by the recognition of the patriarchal sadism within the Godhead which needs the sacrifice of the Son to be transformed in the God of compassion and understanding because only so will it become the Trinity capable of expressing the archetype of alterity. In conclusion, the author follows Jung in the interpretation of the Apocalypse as the shadow of the New Testament and calls attention for Jesus' shadow expressed in His name as symbol of the integration of the Anti-Christ in the myth. ■

El artículo conceptualiza el Arquetipo de la Sombra como el Arquetipo del Mal en la Psicología Simbólica Junguiana y busca integrarlo como expresión del Arquetipo Central, al lado del Arquetipo del Bien. La interpretación de Jung de la limitación de la imagen de Jeovah en la relación con Job es aquí continuada con el reconocimiento del sadismo del Dios patriarcal, que necesita del filicidio sacrificial para transformarse en el Dios de la compasión y del entendimiento, pues sólo así se convertirá en la Trinidad y expresará el Arquetipo de la Alteridad. En conclusión, el autor sigue a Jung en la interpretación del Apocalipsis como la Sombra del Nuevo Testamento y llama la atención sobre el texto ser escrito en el nombre de Jesús, lo que sugiere la integración del símbolo del Anticristo en el mito, como la Sombra de Jesús. ■

Sugars in ferns and lycophytes growing on rocky outcrops from southeastern brazilian coast / Açúcares em samambaias e licófitas crescendo sobre afloramento rochoso da costa sudeste brasileira

The extreme conditions in rocky outcrops allow the occurrence of desiccation tolerant species. One strategy of these plants to withstand water shortage is the accumulation of sugars. In this paper, we report sugar levels and profile of three ferns and one lycophyte naturally hydrated growing on rocky outcrops from Southeastern Brazil. Anemia species have higher sugar contents than Doryopteris collina and Selaginella sellowii. The analyzed species have different sugar profiles. The ferns have glucose, fructose and sucrose, and the lycophyte has glucose and trehalose.

Nas condições ambientais extremas dos afloramentos rochosos ocorrem espécies tolerantes à dessecação. Uma das estratégias dessas plantas para resistir à restrição hídrica é o acúmulo de açúcares. No presente estudo, avaliamos a concentração e o perfil de açúcares de três espécies de samambaias e uma licófita, naturalmente hidratadas crescendo sobre afloramentos rochosos no sudeste do Brasil. As espécies de Anemia possuem maior concentração de açúcares em relação a Doryopteris collina e Selaginella sellowii. As espécies analisadas mostraram perfis distintos de açúcares. As samambaias apresentam glicose, frutose e sacarose, enquanto a licófita glicose e trealose.

Emergence of pyridoxal phosphorylation through a promiscuous ancestor during the evolution of hydroxymethyl pyrimidine kinases.

In the family of ATP-dependent vitamin kinases, several bifunctional enzymes that phosphorylate hydroxymethyl pyrimidine (HMP) and pyridoxal (PL) have been described besides enzymes specific towards HMP. To determine how bifunctionality emerged, we reconstructed the sequence of three ancestors of HMP kinases, experimentally resurrected, and assayed the enzymatic activity of their last common ancestor. The latter has ∼ 8-fold higher specificity for HMP due to a glutamine residue (Gln44) that is a key determinant of the specificity towards HMP, although it is capable of phosphorylating both substrates. These results show how a specific enzyme with catalytic promiscuity gave rise to current bifunctional enzymes.

Avatares da ressurreição dos mortos / Metamorphosis of the resurrection of deaths

Este artigo sublinha a singularidade da invenção da crença na ressurreição dos mortos: esta é aqui examinada sob o ângulo das concepções freudianas do objeto perdido e do luto. A história dessa invenção é retomada desde sua emergência nos primeiros textos bíblicos, seguida de seu florecimento particular com as assombrações, na Idade Média, até seu desenrolar no período moderno e suas manifestações na clínica.

This paper underlines the singularity of the invention of the belief in the resurrection of deaths: this one is examined here taking into consideration Freudian design of the lost object and mourning. The history of this invention is taken again since its emergence in the first biblical texts, its particular efflorescence, with the ghosts, during the Middle Age, until his becoming with the modern period and its expressions in the clinic.

Avatares da ressurreição dos mortos / Metamorphosis of the resurrection of deaths

Este artigo sublinha a singularidade da invenção da crença na ressurreição dos mortos: esta é aqui examinada sob o ângulo das concepções freudianas do objeto perdido e do luto. A história dessa invenção é retomada desde sua emergência nos primeiros textos bíblicos, seguida de seu florecimento particular com as assombrações, na Idade Média, até seu desenrolar no período moderno e suas manifestações na clínica.(AU)

This paper underlines the singularity of the invention of the belief in the resurrection of deaths: this one is examined here taking into consideration Freudian design of the lost object and mourning. The history of this invention is taken again since its emergence in the first biblical texts, its particular efflorescence, with the ghosts, during the Middle Age, until his becoming with the modern period and its expressions in the clinic.(AU)