Aggregator

Per and polyfluoroalkyl substances (PFAS) have emerged as ubiquitous contaminants in municipal solid waste (MSW) landfill leachates due to their widespread industrial applications, environmental persistence, and the disposal of PFAS-containing waste in landfill. This study presents a multi-regional investigation of PFAS occurrence, influencing factors, and treatment performance in 17 landfill leachates and 9 corresponding effluents across China. Sum PFAS concentrations in raw leachates ranged...

Inflammatory diseases of connective tissues such as periodontitis and rheumatoid arthritis exhibit localized destruction of matrix collagen and loss of tissue function. These diseases are driven by interconnected signaling pathways that determine disease progression and severity. Both periodontitis and rheumatoid arthritis involve the release of extracellular Vimentin (ECV) from stromal and immune cells at diseased sites, but the processes by which ECV binds to cells and promotes inflammatory...

CONCLUSIONS: AI-assisted wbMRI interpretation can improve tumor detection in pediatric cancer surveillance by reducing false negatives. However, its influence on workflow efficiency and interradiologist variability highlights the importance of careful implementation. Successful integration requires addressing challenges such as improving the predictive precision of AI models, offering intuitive end-user designs and instructions, and building trust in AI outputs. AI outputs can influence workflow...

Pathogenic variants in the autoimmune regulator (AIRE) cause autoimmune polyendocrine syndrome type 1 (APS-1), a rare primary immunodeficiency disease with symptoms including hypoparathyroidism, adrenal insufficiency, and chronic mucocutaneous candidiasis. AIRE increases the expression and presentation of tissue-specific genes expressing "self" antigens in the developing T cell niche, thus triggering the elimination of self-reactive T cells and preventing autoimmunity. Earlier diagnoses can...

Transcription factors (TFs) are key players in eukaryotic gene regulation, but the DNA binding specificity of many TFs remains unknown. Here, we assay 284 mostly uncharacterized putative human TFs using selective microfluidics-based ligand enrichment followed by sequencing (SMiLE-seq), revealing 74 new DNA binding motifs. To investigate whether TFs lacking detectable motifs preferably bind epigenetically modified DNA, we develop methylation-sensitive SMiLE-seq (meSMiLE-seq), a microfluidic assay...

The functional impact of a large portion of the human genome known as "dark matter DNA", which is composed mainly of repeat sequences, remains unknown. The genome also encodes many putative and poorly characterized transcription factors. Here, we determine genomic binding locations of 166 poorly characterized human transcription factors in living cells. Nearly half of them associate strongly with known regulatory regions such as promoters and enhancers, frequently co-localizing with each other...

Gene expression is regulated by transcription factors (TFs), which recognize specific DNA sequence motifs. Several hundred putative human TFs, identified mainly by an apparent DNA-binding domain, lack known binding motifs¹. Furthermore, even for well-characterized TFs, it remains controversial the degree to which motifs accurately reflect binding sites in living cells². Here we describe a systematic effort ('Codebook') to determine the sequence specificity of 332 putative and poorly...

There is ongoing debate regarding the degree to which transcription factors (TFs) independently specify genomic binding: TF binding motifs are typically short and degenerate, yielding many more binding site predictions than observed in cells. Here we present genomic high-throughput SELEX (GHT-SELEX)-a scalable method that surveys intrinsic binding of purified TFs to the fragmented, naked and unmodified genome. GHT-SELEX peaks for 179 diverse human TFs display surprisingly high overlap with...

Plain Language SummaryResponding to concerns regarding the methods and findings of a study on autism and gender diversity in CanadaDinu and colleagues wrote a letter to the editor about a recently published study that looked at differences in characteristics between autistic and non-autistic adults who were seen by clinicians at a Canadian gender identity clinic. Dinu and colleagues encouraged interpreting the findings of the original article with caution, because they were concerned about the...

CONCLUSIONS: Early program findings suggest that providing hospital-level of care in a community based harm reduction setting may be an acceptable alternative to traditional hospital admission in appropriately selected patients who use drugs.

CONCLUSIONS AND RELEVANCE: In this cohort study of females who underwent BRCA1 or BRCA2 testing, the lifetime cancer risk varied substantially across BRCA test result groups and was further modified by family history. Elevated breast cancer risk among individuals with VUS or negative results highlights the need for individualized risk assessment and management beyond genetic test results alone.

Tioxazafen is an effective nematicide whose commercialization was halted because handlers reportedly developed rashes after working with seeds coated with a tioxazafen-laced cocktail. Here, we show that tioxazafen is bioactivated into toxic products by nematode and human cytochrome P450s. Through systematic analyses, we found that bioactivated tioxazafen disrupts proteasome function, leading to the accumulation of the NRF1 transcription factor ortholog SKN-1A in the nematode C. elegans, and a...

Vision symptoms are frequent after concussion and can often persist and be disabling. Most studies on concussion with persisting concussion symptoms (PCS) provide limited attention to vision symptoms. Vision symptoms occur in 69-82% of patients with PCS and commonly include photophobia, blurred vision, and computer screen intolerance (CSI) - a syndrome induced by viewing electronic screens including computer, cell phone, tablet, or TV screens. We discuss the vision symptoms that may arise and...

Sequence variants in ARID1B, a subunit of the BRG1 (BRM)-associated factors (BAF) complex, are often challenging to classify clinically due to the broad phenotypic spectrum of ARID1B-related disorders (ARID1B-RD). Our previous work has shown that pathogenic variants in epigenetic regulatory genes are associated with DNA methylation (DNAm) signatures, which have proven diagnostic utility for variant classification. Given the role of ARID1B in chromatin remodeling, we profiled whole-blood DNAm for...

CONCLUSIONS AND RELEVANCE: Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

Migrant agricultural workers (MAWs), predominantly individuals from countries in the Global South, play a vital role in maintaining Canadian food security. Employed in low-income positions across the country, they often face workplace hazards and numerous occupational health and safety (OHS) challenges related to long working hours, limited access to OHS information, gaps in knowledge, structural power imbalances with employers, and language and cultural barriers. This pilot study explored the...

Self-fertilization reduces genetic diversity compared to outcrossing and hypothetically decreases the ability to adapt to diverse environments. Among Caenorhabditis nematodes, self-fertilization evolved three times independently in Caenorhabditis elegans, Caenorhabditis briggsae, and the more recently discovered Caenorhabditis tropicalis. To survey C. tropicalis genetic relatedness, the influence of geography and niche on species-wide variation, and the signatures of selection, we collected 785...

CONCLUSION: Using a rat model, our study demonstrates estrogen dependent ERE expression in pre-invasive ER^(+)FOXA1^(+) mammary tumor cells and in circulating immune cells, activation of innate immune responses, and the inhibitory effects of 3TC. ERE RNAs and proteins are also highly expressed in human ER^(+)FOXA1^(+) breast cancers, warranting further investigation into their functions and a potential use of 3TC as a preventive strategy for reducing a risk of cancer progression, especially in...

Spontaneous calcium (Ca^(2+)) waves play a critical role as internal stimuli in the early developing auditory system before the onset of sensory experiences. However, neither the spatiotemporal control of spontaneous Ca^(2+) waves nor their impacts on auditory development are well understood. Here we report that a lateral array of inner supporting cells (ISCs) beneath the inner hair cells displays a spontaneous ultra-long, ultra-fast, transient Ca^(2+) flash, termed "Ca^(2+) lightning", which...

No abstract