Brain connectivity dynamics in cisgender and transmen people with gender incongruence before gender affirmative hormone treatment

Large-scale brain network interactions have been described between trans- and cis-gender binary identities. However, a temporal perspective of the brain's spontaneous fluctuations is missing. We investigated the functional connectivity dynamics in transmen with gender incongruence and its relationship with interoceptive awareness. We describe four states in native and meta-state spaces: (i) one state highly prevalent with sparse overall connections; (ii) a second with strong couplings mainly involving components of the salience, default, and executive control networks. Two states with global sparse connectivity but positive couplings (iii) within the sensorimotor network, and (iv) between salience network regions. Transmen had more dynamical fluidity than cismen, while cismen presented less meta-state fluidity and range dynamism than transmen and ciswomen. A positive association between attention regulation and fluidity and meta-state range dynamism was found in transmen. There exist gender differences in the temporal brain dynamism, characterized by distinct interrelations of the salience network as catalyst interacting with other networks. We offer a functional explanation from the neurodevelopmental cortical hypothesis of a gendered-self.

An in silico approach for structural and functional annotation of matrix protein of Nipah henipavirus: A protein functional analysis

Nipah henipavirus is an emerging RNA virus with increased mortality threatening global security. In South and Southeast Asia, the Nipah virus has caused numerous disease outbreaks. The matrix protein in Nipah henipavirus has an important role, in connecting the viral envelope with the virus core. For virus assembly, linking the viral envelope with the virus core are very crucial. Through functional and structural explanation evaluations, bioinformatics strategies can help us better understanding of the protein. This investigation aims to allocate the structural and functional annotation of protein. Moreover, the investigation attributes physicochemical parameters, three-dimensional structure, and functional annotation of the protein (QBQ56721.1) applying an in silico perspective. The in silico analysis confirmed the protein's hydrophilic nature, with a secondary structure dominated by alpha (α) helices. Based on several quality assessment methodologies, the tertiary-structure model of the protein has been shown to be reasonably consistent. The functional explanation suggested the protein as a structural protein connected to the viral envelope with the virus core, a protein required for virus assembly. This investigation unleashes the significance of the matrix protein (QBQ56721.1) as a functional protein required for Nipah henipavirus.

An in silico approach for structural and functional annotation of matrix protein of Nipah henipavirus: A protein functional analysi

Nipah henipavirus is an emerging RNA virus with increased mortality threatening global security. In South and Southeast Asia, the Nipah virus has caused numerous disease outbreaks. The matrix protein in Nipah henipavirus has an important role, in connecting the viral envelope with the virus core. For virus assembly, linking the viral envelope with the virus core are very crucial. Through functional and structural explanation evaluations, bioinformatics strategies can help us better understanding of the protein. This investigation aims to allocate the structural and functional annotation of protein. Moreover, the investigation attributes physicochemical parameters, three-dimensional structure, and functional annotation of the protein (QBQ56721.1) applying an in silico perspective. The in silico analysis confirmed the protein's hydrophilic nature, with a secondary structure dominated by alpha (α) helices. Based on several quality assessment methodologies, the tertiary-structure model of the protein has been shown to be reasonably consistent. The functional explanation suggested the protein as a structural protein connected to the viral envelope with the virus core, a protein required for virus assembly. This investigation unleashes the significance of the matrix protein (QBQ56721.1) as a functional protein required for Nipah henipavirus.

The Predictive Brain Must Have a Limitation in Short-Term Memory Capacity

Traditionally, short-term memory (STM) has been assessed by asking participants to remember words, visual objects, or numbers for a short amount of time before their recall or recognition of those items is tested. However, this focus on memory for past sensory input might have obscured potential theoretical insights into the function of this cognitive faculty. Here, we suggest that STM may have an important role in predicting future sensory input. This reconceptualization of STM may provide a functional explanation for its capacity limitation.

GWAS-Top Polymorphisms Associated With Late-Onset Alzheimer Disease in Brazil: Pointing Out Possible New Culprits Among Non-Coding RNAs

Several genome-wide association studies (GWAS) have been carried out with late-onset Alzheimer’s disease (LOAD), mainly in European and Asian populations. Different polymorphisms were associated, but several of them without a functional explanation. GWAS are fundamental for identifying loci associated with diseases, although they often do not point to causal polymorphisms. In this sense, functional investigations are a fundamental tool for discovering causality, although the failure of this validation does not necessarily indicate a non-causality. Furthermore, the allele frequency of associated genetic variants may vary widely between populations, requiring replication of these associations in other ethnicities. In this sense, our study sought to replicate in 150 AD patients and 114 elderly controls from the South Brazilian population 18 single-nucleotide polymorphisms (SNPs) associated with AD in European GWAS, with further functional investigation using bioinformatic tools for the associated SNPs. Of the 18 SNPs investigated, only four were associated in our population: rs769449 (APOE), rs10838725 (CELF1), rs6733839, and rs744373 (BIN1–CYP27C1). We identified 54 variants in linkage disequilibrium (LD) with the associated SNPs, most of which act as expression or splicing quantitative trait loci (eQTLs/sQTLs) in genes previously associated with AD or with a possible functional role in the disease, such as CELF1, MADD, MYBPC3, NR1H3, NUP160, SPI1, and TOMM40. Interestingly, eight of these variants are located within long non-coding RNA (lncRNA) genes that have not been previously investigated regarding AD. Some of these polymorphisms can result in changes in these lncRNAs’ secondary structures, leading to either loss or gain of microRNA (miRNA)-binding sites, deregulating downstream pathways. Our pioneering work not only replicated LOAD association with polymorphisms not yet associated in the Brazilian population but also identified six possible lncRNAs that may interfere in LOAD development. The results lead us to emphasize the importance of functional exploration of associations found in large-scale association studies in different populations to base personalized and inclusive medicine in the future.

Emotion Regulation Failures Are Preceded by Local Increases in Sleep-like Activity

Emotion self-regulation relies both on cognitive and behavioral strategies implemented to modulate the subjective experience and/or the behavioral expression of a given emotion. Although it is known that a network encompassing fronto-cingulate and parietal brain areas is engaged during successful emotion regulation, the functional mechanisms underlying failures in emotion suppression (ES) are still unclear. In order to investigate this issue, we analyzed video and high-density EEG recordings of 20 healthy adult participants during an ES and a free expression task performed on two consecutive days. Changes in facial expression during ES, but not free expression, were preceded by local increases in sleep-like activity (1–4 Hz) in brain areas responsible for emotional suppression, including bilateral anterior insula and anterior cingulate cortex, and in right middle/inferior frontal gyrus (p < .05, corrected). Moreover, shorter sleep duration the night before the ES experiment correlated with the number of behavioral errors (p = .03) and tended to be associated with higher frontal sleep-like activity during ES failures (p = .09). These results indicate that local sleep-like activity may represent the cause of ES failures in humans and may offer a functional explanation for previous observations linking lack of sleep, changes in frontal activity, and emotional dysregulation.

Nonsynonymous variations of ion channel-related genes as risk factors in epilepsy

Recurrent seizures are characteristic to epilepsy, which often arise due to increased electrical activity. Ligand-gated ion channels are considered as key factors in epilepsy as they regulate and maintain neuronal membrane potential via regulating ion transportation. Therefore, this study aims to identify ion channel-related single nucleotide variations that are considered as risk factors in epilepsy and determine their potential effects on pathogenicity, protein stability and structure using in silico methods. For this purpose, ion channel-related mutations linked with epilepsy were retrieved from ClinVar. Pathogenicity scores and protein stability were predicted using FATHMM-XF and MUpro, respectively. Structural alterations were determined via HOPE server. We identified 17 epilepsy-related missense mutations, 11 of which were in ion channel-related genes. Nonsynonymous substitutions of p.E177A, p.D219N, p.A322D, p.R577Q, p.E282K, p.V831M and p.R1072C were determined as pathogenic, while all mutations resulted in varying degrees of decrease in overall protein stability. Furthermore, all variants were annotated with risk for disease and introduction of distinct side chains caused differences in size, charge and hydrophobicity, as well as contact with other proteins and ligands. In conclusion, mutations in ion channel-related genes were previously identified in several genetic association studies while their functional annotations were not addressed. The results of this study provide a functional explanation to the pathogenic effects of ion channel-related gene mutations that are considered as risk factors in epilepsy.

Buoyancy control in ammonoid cephalopods refined by complex internal shell architecture

The internal architecture of chambered ammonoid conchs profoundly increased in complexity through geologic time, but the adaptive value of these structures is disputed. Specifically, these cephalopods developed fractal-like folds along the edges of their internal divider walls (septa). Traditionally, functional explanations for septal complexity have largely focused on biomechanical stress resistance. However, the impact of these structures on buoyancy manipulation deserves fresh scrutiny. We propose increased septal complexity conveyed comparable shifts in fluid retention capacity within each chamber. We test this interpretation by measuring the liquid retained by septa, and within entire chambers, in several 3D-printed cephalopod shell archetypes, treated with (and without) biomimetic hydrophilic coatings. Results show that surface tension regulates water retention capacity in the chambers, which positively scales with septal complexity and membrane capillarity, and negatively scales with size. A greater capacity for liquid retention in ammonoids may have improved buoyancy regulation, or compensated for mass changes during life. Increased liquid retention in our experiments demonstrate an increase in areas of greater surface tension potential, supporting improved chamber refilling. These findings support interpretations that ammonoids with complex sutures may have had more active buoyancy regulation compared to other groups of ectocochleate cephalopods. Overall, the relationship between septal complexity and liquid retention capacity through surface tension presents a robust yet simple functional explanation for the mechanisms driving this global biotic pattern.

The Passive Body and States of Nature: An Examination of the Methodological Role State of Nature Theory Plays in Williams and Nietzsche

In his work Truth and Truthfulness, Bernard Williams offers a very different interpretation of philosophical genealogy than that expounded in the secondary literature. The “Received View” of genealogy holds that it is “documentary grey”: it attempts to provide historically well-supported, coherent, but defeasible explanations for the actual transformation of practices, values, and emotions in history. However, paradoxically, the standard interpretation also holds another principle. Genealogies are nevertheless polemical because they admit that any evidence that would serve to justify a genealogical account is indexical to a perspective. In short, genealogies are not true per se. This view of genealogy leaves it vulnerable to three criticisms. I call these three: (1) the reflexive, (2) the substantive, and (3) the semantic. In contrast, Williams argues that all genealogies provide a functional account for the manifestation of something and further, that a State of Nature story subtends these accounts. The upshot of Williams’ approach is that it makes for strange philosophical bedfellows. For example, Nietzsche’s account for the rise of Christian morality shares methodological features with Hobbes’ functional explanation for the emergence of civilization and yet Nietzsche seems to take issue with genealogists who are hypothesis mongers gazing haphazardly into the blue. In the following article, I flesh out, more fully, how to make sense of Williams’ novel reclassification of genealogy. I show that Nietzsche’s genealogies are State of Nature stories and, just like Hobbes’ State of Nature story in chapter thirteen of Leviathan, are subtended by our collective corporeality. I then demonstrate how Nietzsche’s three stories in the Genealogy, when brought together, serve to undermine what Williams refers to as “… a new system (of reasons)—which very powerfully resists being understood in such terms …” Finally, I explain how my reconstruction of Williams’ interpretation of the genealogy immunizes it against the three criticisms noted above.

Brain Connectivity Dynamics in Untreated Transmen and Cisgender Individuals

Large-scale brain network interactions have been described between trans- and cis-gender identities. However, a temporal perspective of the brain spontaneous fluctuations is missing. We investigated the functional connectivity dynamics in transmen with gender incongruence and its relationship with interoceptive awareness. We describe four states in native and meta-state spaces: i) one state highly prevalent with sparse overall connections; ii) a second with strong couplings mainly involving components of the salience, default and executive control networks. Two states with global sparse connectivity but positive couplings iii) within the sensorimotor network, and iv) between salience network regions. Transmen had more dynamical fluidity than cismen, while cismen presented less meta-state fluidity and range dynamism than transmen and ciswomen. A positive association between attention regulation and fluidity, and meta-state range dynamism was found in transmen. There exist gender differences in the temporal brain dynamism, characterized by distinct interrelations of the salience network as catalyst interacting with other networks. We provide a functional explanation to the neurodevelopmental hypothesis proposing different brain phenotypes in the construction of the gendered-self.