familial aggregation

This bibliometric study scrutinizes the corpus of scientific output within the Web of Science pertaining to familial satisfaction among parents raising children with intellectual disabilities, focusing specifically on the milieu of educational inclusion. The analysis discerns a discernible ascension in scholarly interest in this domain, encapsulating 77 papers emanating from 75 journals, incorporating an aggregate of 3,497 cited references. Our investigation delineated 354 researchers across 39 nations, underscoring the transnational purview of this scholarly endeavor...

Alpha-synuclein (αSyn) aggregation and the formation of Lewy pathology (LP) is a foundational pathophysiological phenomenon in synucleinopathies. Delivering therapeutic single-chain and single-domain antibodies that bind pathogenic targets can disrupt intracellular aggregation. The fusion of antibody fragments to a negatively-charged proteasomal targeting motif (PEST) creates bifunctional constructs that enhance both solubility and turnover. With sequence-specific point mutations of PEST sequences that modulate proteasomal degradation efficiency, we report the creation of Programmable Target Antigen Proteolysis (PTAP) technology that can provide graded control over the levels of target antigens...

OBJECTIVE: Lipoprotein glomerulopathy (LPG) is a rare disorder characterized by the development of glomerular lipoprotein thrombosis. LPG exhibits familial aggregation, with mutations in the apolipoprotein E ( APOE ) gene identified as the leading cause of this disease. This study aimed to investigate APOE gene mutations and the clinicopathological features in eleven LPG patients. METHODS: Clinicopathological and follow-up data were obtained by extracting DNA, followed by APOE coding region sequencing analysis...

AIMS: To determine whether a family history of unexplained heart failure (HF) in first-degree relatives (children or sibling) increases the rate of unexplained HF. METHODS AND RESULTS: Using Danish nationwide registry data (1978-2017), we identified patients (probands) diagnosed with first unexplained HF (HF without any known comorbidities) in Denmark, and their first-degree relatives. All first-degree relatives were followed from the HF date of the proband and until an event of unexplained HF, exclusion diagnosis, death, emigration, or study end, whichever occurred first...

Human ATP-binding cassette (ABC) transporters are one of the largest families of membrane proteins and perform diverse functions. Many of them are associated with multidrug resistance that often results in cancer treatment with poor outcomes. Here, we present the structural bioinformatics study of six human ABC membrane transporters with experimentally determined cryo-electron microscopy (CryoEM) structures including ABCB7, ABCC8, ABCD1, ABCD4, ABCG1, ABCG5, and their AlphaFold2-predicted water-soluble QTY variants...

BACKGROUND: Research on the health and economic costs due to insufficient sleep remains scant in developing countries. In this study we aimed to estimate the years of life lost (YLLs) due to short sleep and quantify its economic burden in China. METHODS: We estimated both individual and aggregate YLLs due to short sleep (ie, ≤6 hours) among Chinese adults aged 20 years or older by sex and five-year age groups in 2010, 2014, and 2018. YLL estimates were derived from 1) the prevalence of short sleep using three survey waves of the China Family Panel Studies, 2) relative mortality risks from meta-analyses, and 3) life tables in China...

The SERF family of proteins were originally discovered for their ability to accelerate amyloid formation. Znf706 is an uncharacterized protein whose N-terminus is homologous to SERF proteins. We show here that human Znf706 can promote protein aggregation and amyloid formation. Unexpectedly, Znf706 specifically interacts with stable, non-canonical nucleic acid structures known as G-quadruplexes. G-quadruplexes can affect gene regulation and suppress protein aggregation; however, it is unknown if and how these two activities are linked...

The tidal occurrence of larval fishes was investigated in the permanently open Kowie Estuary on the warm-temperate coast of South Africa. Larval fishes were sampled in the mouth region using two drifting light traps deployed on the ebb and flood tides every second night for two consecutive 14-day periods, coinciding with the dark moon phase. A total of 553 larval fishes were caught, representing nine families and 26 species, of which Blenniidae and Clupeidae dominated. The prevalence of different estuarine association fish guilds was also tide-specific...

Protein misfolding and mislocalization are common themes in neurodegenerative disorders, including the motor neuron disease, amyotrophic lateral sclerosis (ALS). Maintaining proteostasis is a crosscutting therapeutic target, including upregulation of heat shock proteins (HSP) to increase chaperoning capacity. Motor neurons have a high threshold for upregulating stress inducible HSPA1A, but constitutively express high levels of HSPA8. This study compared expression of these HSPs in cultured motor neurons expressing three variants linked to familial ALS: TDP-43G348C , FUSR521G or SOD1G93A ...

Gut microbial communities are critical in determining the evolutive success of fruit fly phytophagous pests (Diptera, Tephritidae), facilitating their adaptation to suboptimal environmental conditions and to plant allelochemical defences. An important source of variation for the microbial diversity of fruit flies is represented by the crop on which larvae are feeding. However, a "crop effect" is not always the main driver of microbial patterns, and it is often observed in combination with other and less obvious processes...

Aggregation of α-synuclein (α-syn) and α-syn cytotoxicity are hallmarks of sporadic and familial Parkinson's disease (PD). Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-dependent enhancement of the expression of the 20S proteasome core particles (20S CPs) and regulatory particles (RPs) increases proteasome activity, which can promote α-syn clearance in PD. Activation of peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) may reduce oxidative stress by strongly inducing Nrf2 gene expression...

Nuptial glands are very diverse and associated with different pollination mechanisms. The greater the specificity in the pollen transfer mechanism from anther to stigma, the greater the morphological elaboration of flowers and functional complexity of the nuptial glands. In Apocynaceae, pollination mechanisms reached an extreme specificity, a fact that was only possible due to an extreme morphological synorganization and a profusion of floral glands. Although these glands are of different types, the vast majority have secretory cells only in the epidermis...

RNA-binding proteins (RBPs)-RNA networks have contributed to cancer development. Circular RNAs (circRNAs) are considered as protein recruiters; nevertheless, the patterns of circRNA-protein interactions in colorectal cancer (CRC) are still lacking. Processing bodies (PBs) formed through liquid-liquid phase separation (LLPS) are membrane-less organelles (MLOs) consisting of RBPs and RNA. Previous evidence suggests a connection between PBs dynamics and cancer progression. Despite the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs, there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in CRC...

Accurate prediction of small molecule modulators targeting protein-protein interactions (PPIMs) remains a significant challenge in drug discovery. Existing machine learning-based models rely on manual feature engineering, which is tedious and task-specific. Recently, deep learning models based on graph neural networks have made remarkable progress in molecular representation learning. However, many graph-based approaches ignore molecular hierarchical structure modeling guided by domain knowledge. In chemistry, the functional groups of a molecule determine its interaction with specific targets...

BACKGROUND: Despite the availability of evidence-based and effective treatments, significant numbers of people living with mental illness do not receive treatment or do not seek help from providers of formal modern treatment. Although numerous primary studies have been conducted on patterns of help-seeking behavior among individuals with mental illness with respect to modern therapy, the evidence has not been aggregated nationwide. Therefore, the aim of this review was to investigate pooled data on patterns of help-seeking behavior among individuals with mental illness in Ethiopia...

BACKGROUND: Type 1 diabetes in children is known to be highly heritable, but much less is known about the heritability of adult-onset type 1 diabetes. Thus, our objective was to compare the familial aggregation and heritability of type 1 diabetes in adults and children. METHODS: This Swedish nationwide register-based cohort study included individuals born from Jan 1, 1982, to Dec 31, 2010, identified through the Medical Birth Register who were linked to their parents, full siblings, half siblings, and cousins through the Multi-Generation Register (MGR)...

Objective: To investigate the clinicopathological and molecular genetic characteristics of Crohn's disease (CD). Methods: A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes...

Adult individuals with Down syndrome (DS) develop Alzheimer disease (AD). Whether there is a difference between AD in DS and AD regarding the structure of amyloid-β (Aβ) and tau filaments is unknown. Here we report the structure of Aβ and tau filaments from two DS brains. We found two Aβ40 filaments (types IIIa and IIIb) that differ from those previously reported in sporadic AD and two types of Aβ42 filaments (I and II) identical to those found in sporadic and familial AD. Tau filaments (paired helical filaments and straight filaments) were identical to those in AD, supporting the notion of a common mechanism through which amyloids trigger aggregation of tau...

MNGIE (Mitochondrial Neurogastrointestinal Encephalomyopathy) is an ultra-rare autosomal recessive disorder that leads to mutations in the nuclear genes encoding thymidine phosphorylase. Symptoms include gastrointestinal dysmotility, cachexia, ptosis, external ophthalmoplegia, sensorimotor neuropathy and asymptomatic leukoencephalopathy. We describe the first case of MNGIE with meningoencephalitis that ultimately led to a familial diagnosis ending a diagnostic odyssey. We retrospectively reviewed the electronic medical records and sent whole exome sequencing for the index case and his family members...

Alzheimer's disease (AD) and traumatic brain injury (TBI) are major public health issues worldwide, with over 38 million people living with AD and approximately 48 million people (27-69 million) experiencing TBI annually. Neurodegenerative conditions are characterised by the accumulation of neurotoxic amyloid beta (Aβ) and microtubule-associated protein Tau (Tau) with current treatments focused on managing symptoms rather than addressing the underlying cause. Heparan sulfate proteoglycans (HSPGs) are a diverse family of macromolecules that interact with various proteins and ligands and promote neurogenesis, a process where new neural cells are formed from stem cells...