PLIP 2021: expanding the scope of the protein-ligand interaction profiler to DNA and RNA.

With the growth of protein structure data, the analysis of molecular interactions between ligands and their target molecules is gaining importance. PLIP, the protein-ligand interaction profiler, detects and visualises these interactions and provides data in formats suitable for further processing. PLIP has proven very successful in applications ranging from the characterisation of docking experiments to the assessment of novel ligand-protein complexes. Besides ligand-protein interactions, interactions with DNA and RNA play a vital role in many applications, such as drugs targeting DNA or RNA-binding proteins. To date, over 7% of all 3D structures in the Protein Data Bank include DNA or RNA. Therefore, we extended PLIP to encompass these important molecules. We demonstrate the power of this extension with examples of a cancer drug binding to a DNA target, and an RNA-protein complex central to a neurological disease. PLIP is available online at https://plip-tool.biotec.tu-dresden.de and as open source code. So far, the engine has served over a million queries and the source code has been downloaded several thousand times.

Recognition memory is associated with altered resting-state functional connectivity in people at genetic risk for Alzheimer's disease.

The apolipoprotein E ε4 (ApoE ε4) allele not only represents the strongest single genetic risk factor for sporadic Alzheimer's disease, but also imposes independent effects on brain function in healthy individuals where it has been shown to promote subtle memory deficits and altered intrinsic functional brain network connectivity. Based on previous work showing a potential relevance of the default mode network (DMN) functional connectivity for episodic memory function, we hypothesized that the ApoE ε4 genotype would affect memory performance via modulation of the DMN. We assessed 63 healthy individuals (50-80 years old), of which 20 carried the ε4 allele. All participants underwent resting-state functional magnetic resonance imaging (fMRI), high-resolution 3D anatomical MRI imaging and neuropsychological assessment. Functional connectivity analysis of resting-state activity was performed with a predefined seed region located in the left posterior cingulate cortex (PCC), a core region of the DMN. ApoE ε4 carriers performed significantly poorer than non-carriers in wordlist recognition and cued recall. Furthermore, ε4 carriers showed increased connectivity relative to ε4 non-carriers between the PCC seed region and left-hemispheric middle temporal gyrus (MTG). There was a positive correlation between recognition memory scores and resting-state connectivity in the left MTG in ε4 carriers. These results can be interpreted as compensatory mechanisms strengthening the cross-links between DMN core areas and cortical areas involved in memory processing.

Fobia: um sintoma marcado pelo real / Phobia: a sympton marked by real

O artigo pretende introduzir o questionamento acerca dos sintomas marcados pelo real, a partir da análise do sintoma fóbico do caso clínico de Freud, o “Pequeno Hans”. Por um lado, o sintoma como formação de compromisso (Freud), e como formação do inconsciente (Lacan), vem no lugar de algo que não pode ser sabido pelo sujeito, isto que é recalcado e endereçado ao Outro. Por outro, a fobia traz a particularidade de ser marcada por um real, carente de interdição paterna, sem visar um deciframento por parte do sujeito.

This article brings up questions about symptoms marked by the real, based on Freud's case of "Little Hans", where Freud analysis the boy's phobic symptom. On the one hand, we can say that a symptom is a compromise formation(Freud), and that, as an unconscious formation (Lacan), it replaces something that cannot come to the subject's knowledge, something repressed and addressed to the Other. On the other hand, phobia has the specific aspect of being marked by the real, the lack paternal intervention, without the subject's attempt to solve it.

Fobia: um sintoma marcado pelo real / Phobia: a sympton marked by real

O artigo pretende introduzir o questionamento acerca dos sintomas marcados pelo real, a partir da análise do sintoma fóbico do caso clínico de Freud, o “Pequeno Hans”. Por um lado, o sintoma como formação de compromisso (Freud), e como formação do inconsciente (Lacan), vem no lugar de algo que não pode ser sabido pelo sujeito, isto que é recalcado e endereçado ao Outro. Por outro, a fobia traz a particularidade de ser marcada por um real, carente de interdição paterna, sem visar um deciframento por parte do sujeito(AU)

This article brings up questions about symptoms marked by the real, based on Freud's case of "Little Hans", where Freud analysis the boy's phobic symptom. On the one hand, we can say that a symptom is a compromise formation(Freud), and that, as an unconscious formation (Lacan), it replaces something that cannot come to the subject's knowledge, something repressed and addressed to the Other. On the other hand, phobia has the specific aspect of being marked by the real, the lack paternal intervention, without the subject's attempt to solve it (AU)

Angústia e objeto: elaborações a partir do caso de fobia Pequeno Hans / Anguish and object: - considerations based on the phobia case Little Hans

De acordo com a teoria freudiana em sua abordagem por Lacan, os conceitos “angústia” e “objeto” são articulados sob dois aspectos na presente dissertação. Primeiro, a partir de um exame das considerações de Freud a respeito da fobia, que liga a angústia a um objeto na realidade. Com a formulação do “objeto a” por Lacan, constata-se uma transformação do estatuto do objeto, uma vez que se trata de um objeto inconsistente. Exploramos, então, as possíveis relações entre a fobia do caso “Pequeno Hans” e tal objeto (AU)