Developing Generalizable Scoring Functions for Molecular Docking: Challenges and Perspectives.

Structure-based drug discovery methods, such as molecular docking and virtual screening, have become invaluable tools in developing novel drugs. At the core of these methods are Scoring Functions (SFs), which predict the binding affinity between ligands and protein targets. This study aims to review and contextualize the challenges and best practices in training novel scoring functions to improve their accuracy and generalizability in predicting protein-ligand binding affinities.

SAnDReS 2.0: Development of machine-learning models to explore the scoring function space.

Classical scoring functions may exhibit low accuracy in determining ligand binding affinity for proteins. The availability of both protein-ligand structures and affinity data make it possible to develop machine-learning models focused on specific protein systems with superior predictive performance. Here, we report a new methodology named SAnDReS that combines AutoDock Vina 1.

The impact of COVID-19 childhood and adolescent vaccination on mortality in Argentina.

Introduction: Argentina authorized COVID-19 vaccination for adolescents 12 years and older in August 2021, and then for children three years and older in October 2021. Children aged 6 months-2 years received a two-dose regimen beginning July 2022.

Objective: This study aims to analyze the impact of COVID-19 vaccination among children aged 0-17, considering vaccination status and mortality for the 2020-2022 period.

A novel missense mutation in the AIRE gene underlying autoimmune polyglandular syndrome type 1.

The immune regulator gene AIRE plays an essential role in the establishment of immune tolerance and the prevention of autoimmunity. This transcription factor plays a critical role in promoting self-tolerance in the thymus by regulating the expression of a large number of self-antigens that share the common feature of being tissue-restricted in their expression pattern in the periphery. Dysfunction of AIRE in humans causes a rare disease, autoimmune polyglandular syndrome type 1 (APS1), characterized by an autoimmune response against peripheral tissues, particularly endocrine tissues.

Exploring Scoring Function Space: Developing Computational Models for Drug Discovery.

Background: The idea of scoring function space established a systems-level approach to address the development of models to predict the affinity of drug molecules by those interested in drug discovery.

Objective: Our goal here is to review the concept of scoring function space and how to explore it to develop machine learning models to address protein-ligand binding affinity.

Methods: We searched the articles available in PubMed related to the scoring function space.

Convergent Evolution in SARS-CoV-2 Spike Creates a Variant Soup from Which New COVID-19 Waves Emerge.

The first 2 years of the COVID-19 pandemic were mainly characterized by recurrent mutations of SARS-CoV-2 Spike protein at residues K417, L452, E484, N501 and P681 emerging independently across different variants of concern (Alpha, Beta, Gamma, and Delta). Such homoplasy is a marker of convergent evolution. Since Spring 2022 and the third year of the pandemic, with the advent of Omicron and its sublineages, convergent evolution has led to the observation of different lineages acquiring an additional group of mutations at different amino acid residues, namely R346, K444, N450, N460, F486, F490, Q493, and S494.

When shared concept cells support associations: Theory of overlapping memory engrams.

Assemblies of neurons, called concepts cells, encode acquired concepts in human Medial Temporal Lobe. Those concept cells that are shared between two assemblies have been hypothesized to encode associations between concepts. Here we test this hypothesis in a computational model of attractor neural networks.

COVID-19 mitigation by digital contact tracing and contact prevention (app-based social exposure warnings).

A plethora of measures are being combined in the attempt to reduce SARS-CoV-2 spread. Due to its sustainability, contact tracing is one of the most frequently applied interventions worldwide, albeit with mixed results. We evaluate the performance of digital contact tracing for different infection detection rates and response time delays.

Searching for the neural correlates of human intelligence.

In this My Word, Rodrigo Quian Quiroga discusses neural mechanisms underlying human memory and uniquely human cognitive abilities.

Bioinformatic Identification of Functionally and Structurally Relevant Residues and Motifs in Protein S-Acyltransferases.

DHHC palmitoyltransferases (DHHC-PATs) are very peculiar in that, outside the DHHC domain, they are very divergent even across orthologs from closely related species. This represents a challenge for the bioinformatic analyses of these proteins. Sequence-based analyses and predictions require a valid sequence alignment, which for this family of proteins requires extensive manual curation and this is difficult to attain for the nonspecialist.

Compact standalone platform for neural recording with real-time spike sorting and data logging.

Objective: Longitudinal observation of single unit neural activity from large numbers of cortical neurons in awake and mobile animals is often a vital step in studying neural network behaviour and towards the prospect of building effective brain-machine interfaces (BMIs). These recordings generate enormous amounts of data for transmission and storage, and typically require offline processing to tease out the behaviour of individual neurons. Our aim was to create a compact system capable of: (1) reducing the data bandwidth by circa 2 to 3 orders of magnitude (greatly improving battery lifetime and enabling low power wireless transmission in future versions); (2) producing real-time, low-latency, spike sorted data; and (3) long term untethered operation.

Improving data quality in neuronal population recordings.

Understanding how the brain operates requires understanding how large sets of neurons function together. Modern recording technology makes it possible to simultaneously record the activity of hundreds of neurons, and technological developments will soon allow recording of thousands or tens of thousands. As with all experimental techniques, these methods are subject to confounds that complicate the interpretation of such recordings, and could lead to erroneous scientific conclusions.

Magic and cognitive neuroscience.

In recent years, neuroscientists have shown an increasing interest in magic. One reason for this is the parallels that can be drawn between concepts that have long been discussed in magic theory, particularly misdirection, and those that are routinely studied in cognitive neuroscience, such as attention and, as argued in this essay, different forms of memory. A second and perhaps more attractive justification for this growing interest is that magic tricks offer novel experimental approaches to cognitive neuroscience.

Vinardo: A Scoring Function Based on Autodock Vina Improves Scoring, Docking, and Virtual Screening.

Autodock Vina is a very popular, and highly cited, open source docking program. Here we present a scoring function which we call Vinardo (Vina RaDii Optimized). Vinardo is based on Vina, and was trained through a novel approach, on state of the art datasets.

Gnostic cells in the 21st century.

In this short review, I revise the notion of gnostic cells posited by Konorski, together with similar arguments by James, Lettvin and Barlow--namely, the idea of pontifical, grandmother and cardinal cells, respectively. I then discuss whether the characteristics of the recently discovered concept cells, i.e.

Looking for a face in the crowd: fixation-related potentials in an eye-movement visual search task.

Despite the compelling contribution of the study of event related potentials (ERPs) and eye movements to cognitive neuroscience, these two approaches have largely evolved independently. We designed an eye-movement visual search paradigm that allowed us to concurrently record EEG and eye movements while subjects were asked to find a hidden target face in a crowded scene with distractor faces. Fixation event-related potentials (fERPs) to target and distractor stimuli showed the emergence of robust sensory components associated with the perception of stimuli and cognitive components associated with the detection of target faces.

Short transmembrane domains with high-volume exoplasmic halves determine retention of Type II membrane proteins in the Golgi complex.

It is still unclear why some proteins that travel along the secretory pathway are retained in the Golgi complex whereas others make their way to the plasma membrane. Recent bioinformatic analyses on a large number of single-spanning membrane proteins support the hypothesis that specific features of the transmembrane domain (TMD) are relevant to the sorting of these proteins to particular organelles. Here we experimentally test this hypothesis for Golgi and plasma membrane proteins.

Zinc co-ordination by the DHHC cysteine-rich domain of the palmitoyltransferase Swf1.

S-acylation, commonly known as palmitoylation, is a widespread post-translational modification of proteins that consists of the thioesterification of one or more cysteine residues with fatty acids. This modification is catalysed by a family of PATs (palmitoyltransferases), characterized by the presence of a 50-residue long DHHC-CRD (Asp-His-His-Cys cysteine-rich domain). To gain knowledge on the structure-function relationships of these proteins, we carried out a random-mutagenesis assay designed to uncover essential amino acids in Swf1, the yeast PAT responsible for the palmitoylation of SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) proteins.

A detailed and fast model of extracellular recordings.

We present a novel method to generate realistic simulations of extracellular recordings. The simulations were obtained by superimposing the activity of neurons placed randomly in a cube of brain tissue. Detailed models of individual neurons were used to reproduce the extracellular action potentials of close-by neurons.

Vacuolar protein sorting receptor in Giardia lamblia.

In Giardia, lysosome-like peripheral vacuoles (PVs) need to specifically coordinate their endosomal and lysosomal functions to be able to successfully perform endocytosis, protein degradation and protein delivery, but how cargo, ligands and molecular components generate specific routes to the PVs remains poorly understood. Recently, we found that delivering membrane Cathepsin C and the soluble acid phosphatase (AcPh) to the PVs is adaptin (AP1)-dependent. However, the receptor that links AcPh and AP1 was never described.

Medicinal ethnobotany in Huacareta (Chuquisaca, Bolivia).

Background: The aim of this study was to document the types of diseases treated by the use of medicinal plants, their main applications and also to have a report of the major diseases treated at the Hospital of San Pablo de Huacareta (Chuquisaca Bolivia).

Methods: We conducted semi-structured interviews on the use medicinal plants with 10 local informants, and categorized the kinds of diseases treated by traditional medicine. We obtained reports of cases treated at the Hospital of Huacareta in order to compare the use frequency of traditional medicine and allopathic medicine for the treatment of recurrent diseases in the area.

Fixation-related potentials in visual search: a combined EEG and eye tracking study.

We report a study of concurrent eye movements and electroencephalographic (EEG) recordings while subjects freely explored a search array looking for hidden targets. We describe a sequence of fixation-event related potentials (fERPs) that unfolds during ∼ 400 ms following each fixation. This sequence highly resembles the event-related responses in a replay experiment, in which subjects kept fixation while a sequence of images occurred around the fovea simulating the spatial and temporal patterns during the free viewing experiment.