After a sexual assault, survivors have the option of seeking a medical forensic exam, which includes medical evaluation and treatment, as well as forensic evidence collection. Forensic evidence is collected in a sexual assault evidence kit (SAEK) and typically released to police to aid in the investigation and potential prosecution of the assault. However, 20% to 25% of survivors who have a SAEK collected do not report their assault to police at that time and choose instead to have their SAEK stored for possible future use.
View Article and Find Full Text PDFStudy Question: Can the accuracy of timing of luteal phase endometrial biopsies based on urinary ovulation testing be improved by measuring the expression of a small number of genes and a continuous, non-categorical modelling approach?
Summary Answer: Measuring the expression levels of six genes (IL2RB, IGFBP1, CXCL14, DPP4, GPX3 and SLC15A2) is sufficient to obtain substantially more accurate timing estimates and to assess the reliability of timing estimates for each sample.
What Is Known Already: Commercially available endometrial timing approaches based on gene expression require large gene sets and use a categorical approach that classifies samples as pre-receptive, receptive or post-receptive.
Study Design, Size, Duration: Gene expression was measured by RTq-PCR in different sample sets, comprising a total of 664 endometrial biopsies obtained 4-12 days after a self-reported positive home ovulation test.
Decidual remodelling of midluteal endometrium leads to a short implantation window after which the uterine mucosa either breaks down or is transformed into a robust matrix that accommodates the placenta throughout pregnancy. To gain insights into the underlying mechanisms, we established and characterized endometrial assembloids, consisting of gland-like organoids and primary stromal cells. Single-cell transcriptomics revealed that decidualized assembloids closely resemble midluteal endometrium, harbouring differentiated and senescent subpopulations in both glands and stroma.
View Article and Find Full Text PDFFAN1, a DNA structure-specific nuclease, interacts with MLH1, but the repair pathways in which this complex acts are unknown. FAN1 processes DNA interstrand crosslinks (ICLs) and FAN1 variants are modifiers of the neurodegenerative Huntington's disease (HD), presumably by regulating HD-causing CAG repeat expansions. Here, we identify specific amino acid residues in two adjacent FAN1 motifs that are critical for MLH1 binding.
View Article and Find Full Text PDFRAS mutations are the most common oncogenic drivers across human cancers, but there remains a paucity of clinically-validated pharmacological inhibitors of RAS, as druggable pockets have proven difficult to identify. Here, we identify two RAS-binding Affimer proteins, K3 and K6, that inhibit nucleotide exchange and downstream signaling pathways with distinct isoform and mutant profiles. Affimer K6 binds in the SI/SII pocket, whilst Affimer K3 is a non-covalent inhibitor of the SII region that reveals a conformer of wild-type RAS with a large, druggable SII/α3 pocket.
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