behavioral variant

Uterine smooth muscle tumors are a heterogeneous group of mesenchymal neoplasms with multiple histologic variants and distinct biological behaviors. Pathologic classification (benign, uncertain malignant potential, malignant) relies on the evaluation of mitotic index, necrosis, and degree of cytologic atypia, with different thresholds based on each subtype. Immunohistochemistry and other ancillary studies may be necessary to establish the diagnosis in a subset of cases, given the morphologic overlap with other mesenchymal neoplasms, including low-grade and high-grade endometrial stromal tumors, inflammatory myofibroblastic tumors, and PEComa...

Humans evolved an extraordinarily expanded and complex cerebral cortex, associated with developmental and gene regulatory modifications 1-3 . Human accelerated regions (HARs) are highly conserved genomic sequences with human-specific nucleotide substitutions. Although there are thousands of annotated HARs, their functional contribution to human-specific cortical development is largely unknown 4,5 . HARE5 is a HAR transcriptional enhancer of the WNT signaling receptor Frizzled8 (FZD8) active during brain development 6 ...

There is considerable comorbidity across externalizing and internalizing behavior dimensions of psychopathology. We applied genomic structural equation modeling (gSEM) to genome-wide association study (GWAS) summary statistics to evaluate the factor structure of externalizing and internalizing psychopathology across 16 traits and disorders among European-ancestry individuals (n's = 16,400 to 1,074,629). We conducted GWAS on factors derived from well-fitting models. Downstream analyses served to identify biological mechanisms, explore drug repurposing targets, estimate genetic overlap between the externalizing and internalizing spectra, and evaluate causal effects of psychopathology liability on physical health...

Behavioral variant frontotemporal dementia (bvFTD) is a clinical syndrome primarily caused by either tau (bvFTD-tau) or TDP-43 (bvFTD-TDP) proteinopathies. We previously found lower cortical layers and dorsolateral regions accumulate greater tau than TDP-43 pathology; however, patterns of laminar neurodegeneration across diverse cytoarchitecture in bvFTD is understudied. We hypothesized that bvFTD-tau and bvFTD-TDP have distinct laminar distributions of pyramidal neurodegeneration along cortical gradients, a topologic order of cytoarchitectonic subregions based on increasing pyramidal density and laminar differentiation...

Variants in KCNT1 are associated with a wide spectrum of epileptic phenotypes, including epilepsy of infancy with migrating focal seizures (EIMFS), non-EIMFS developmental and epileptic encephalopathies, autosomal dominant or sporadic sleep-related hypermotor epilepsy, and focal epilepsy. Here, we describe a girl affected by drug-resistant focal seizures, developmental delay and behavior disorders, caused by a novel, de novo heterozygous missense KCNT1 variant (c.2809A > G, p.S937G). Functional characterization in transiently transfected Chinese Hamster Ovary (CHO) cells revealed a strong gain-of-function effect determined by the KCNT1 p...

BACKGROUND: Recent genetic evidence supports that circulating biochemical and metabolic traits (BMTs) play a causal role in Alzheimer's disease (AD), which might be mediated by changes in brain structure. Here, we leveraged publicly available genome-wide association study data to investigate the intrinsic causal relationship between blood BMTs, brain image-derived phenotypes (IDPs) and AD. METHODS: Utilizing the genetic variants associated with 760 blood BMTs and 172 brain IDPs as the exposure and the latest AD summary statistics as the outcome, we analyzed the causal relationship between blood BMTs and brain IDPs and AD by using a two-sample Mendelian randomization (MR) method...

Cells from different organs in the body experience a range of mechanical and osmotic pressures that change in various diseases, including neurological, cardiovascular, ophthalmological, and renal diseases. Here, we demonstrate the use of an engineered Sensor-Actuator-Modulator (SAM) of microbial origin derived from a mechanosensitive channel of large conductance (MscL) for sensing external mechanical stress and modulating activities of mammalian cells. SAM is reliably expressed in the mammalian cell membrane and acts as a tension-activated pressure release valve...

Eating disorders (EDs) are a type of psychiatric disorder characterized by pathological eating and related behavior and considered to be highly heritable. The purpose of this study was to explore rare variants expected to display biological functions associated with the etiology of EDs. We performed whole exome sequencing (WES) of affected sib-pairs corresponding to disease subtype through their lifetime and their parents. From those results, rare single nucleotide variants (SNVs) concordant with sib-pairs were extracted and estimated to be most deleterious in the examined families...

PURPOSE: GM1 gangliosidosis (GM1) a lysosomal disorder caused by pathogenic variants in GLB1, is characterized by relentless neurodegeneration. There are no approved treatments. METHODS: Forty-one individuals with type II (late-infantile and juvenile) GM1 participated in a single-site prospective observational study. RESULTS: Classification of 37 distinct variants using ACMG criteria resulted in the upgrade of six and the submission of four new variants...

Frontal variant Alzheimer's disease (AD) manifests with either behavioral or dysexecutive syndromes. Recent efforts to gain a deeper understanding of this phenotype have led to a re-conceptualization of frontal AD. Behavioral (bAD) and dysexecutive (dAD) phenotypes could be considered subtypes, as suggested by both clinical and neuroimaging studies. In this review, we focused on imaging studies to highlight specific brain patterns in these two uncommon clinical AD phenotypes. Although studies did not compare directly these two variants, a common epicenter located in the frontal cortex could be inferred...

This research evaluated the relationship between daily new Coronavirus Disease 2019 (COVID-19) cases and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) concentrations in wastewater, followed by effects of differential SARS-CoV-2 shedding loads across various COVID-19 outbreaks. Linear regression analyses were utilized to examine the lead time of the SARS-CoV-2 signal in wastewater relative to new COVID-19 clinical cases. During the Delta wave, no lead time was evident, highlighting limited predictive capability of wastewater monitoring during this phase...

INTRODUCTION: Potato ( Solanum tuberosum L.), the fourth most important food crop in the world, is affected by several viral pathogens with potato virus Y (PVY) having the greatest economic impact. At least nine biologically distinct variants of PVY are known to infect potato. These include the relatively new recombinant types named PVY-NTN and PVYN-Wi, which induce tuber necrosis in susceptible cultivars. To date, the molecular plant-virus interactions underlying this pathogenicity have not been fully characterized...

Cardiovascular diseases (CVD) represent a major health problem worldwide. In Italy, despite the decline in CVD mortality and disability-adjusted life years recently observed, CVD remains the leading cause of death. The development of CVD has a complex and multifactorial etiology that involves environmental, lifestyle/behavioral (e.g., unhealthy diet, physical inactivity, smoking, and alcohol abuse), metabolic, and genetic factors. Although a large number of CVD susceptibility genetic variants have been identified, some seem to confer risk according to the genetic background or ethnicity of the population...

Recent integrative multilevel models offer novel insights into the etiology and course of neurodegenerative conditions. The predictive coding of allostatic-interoception theory posits that the brain adapts to environmental demands by modulating internal bodily signals through the allostatic-interoceptive system. Specifically, a domain-general allostatic-interoceptive network exerts adaptive physiological control by fine-tuning initial top-down predictions and bottom-up peripheral signaling. In this context, adequate adaptation implies the minimization of prediction errors thereby optimizing energy expenditure...

Substantial progress has been made in understanding the genetic architecture of phenotypes involved in a variety of evolutionary processes. Behavioral genetics remains, however, among the least understood. We explore the genetic architecture of spatial cognitive abilities in a wild passerine bird, the mountain chickadee (Poecile gambeli). Mountain chickadees cache thousands of seeds in the fall and require specialized spatial memory to recover these caches throughout the winter. We previously showed that variation in spatial cognition has a direct effect on fitness and has a genetic basis...

Secretoglobin (SCGB) 3A2 belongs to an intriguing family of small, secreted proteins present only in mammals. Although members of the SCGB protein family have distinct amino-acid sequences, they share structural similarities. Of particularly interest is the not yet fully understood self-assembly ability of SCGBs, which arise from covalent disulfide dimerization and non-covalent oligomerization. Recently, SCGB3A2 has attracted attention for its singular expression profile in airways. However, the knowledge on SCGB3A2 (patho)physiology derives exclusively from in-vivo and complex ex-vivo mixtures, which hampers characterization of the mechanisms driving SCGB3A2 structural behavior...

ASH1L potentially contributes to Tourette syndrome (TS) and other neuropsychiatric disorders, as our previous studies have shown. It regulates essential developmental genes by counteracting polycomb-mediated transcriptional repression, which restricts chromatin accessibility at target genes. ASH1L is highly expressed in the adult brain, playing a crucial role in the early stage. However, it remains unclear how ASH1L mutations carried by patients with TS participate in regulating neuronal growth processes leading to TS traits...

Individuals with bipolar disorder are at increased risk for suicide, and this can be influenced by a range of biological, clinical, and environmental risk factors. Biological components associated with suicide include DNA modifications that lead to changes in gene expression. Common genetic variation and DNA methylation changes are some of the most frequent types of DNA findings associated with an increased risk for suicidal behavior. Importantly, the interplay between genetic predisposition and DNA methylation patterns is becoming more prevalent in genetic studies...

BACKGROUND: SARS-CoV-2 vaccines have been shown to be safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination. In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. We performed this study to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population...

Pathogenic variants in SLC6A8, the gene which encodes creatine transporter SLC6A8, prevent creatine uptake in the brain and result in a variable degree of intellectual disability, behavioral disorders (e.g., autism spectrum disorder), epilepsy, and severe speech and language delay. There are no treatments to improve neurodevelopmental outcomes for creatine transporter deficiency (CTD). In this spotlight, we summarize recent advances in innovative molecules to treat CTD, with a focus on dodecyl creatine ester, the most promising drug candidate...