Plasma p-tau217 predicts cognitive impairments up to ten years before onset in normal older adults.

Importance: Positron emission tomography (PET) biomarkers are the gold standard for detection of Alzheimer amyloid and tau . Such imaging can identify cognitively unimpaired (CU) individuals who will subsequently develop cognitive impartment (CI). Plasma biomarkers would be more practical than PET or even cerebrospinal fluid (CSF) assays in clinical settings.

Live births in women with recurrent hydatidiform mole and two NLRP7 mutations.

Hydatidiform mole (HM) is an aberrant human pregnancy with abnormal embryonic development and excessive proliferation of the trophoblast. Recessive mutations in NLRP7 are responsible for recurrent HM (RHM). Women with recessive NLRP7 mutations fail to have normal pregnancies from spontaneous conceptions with the exception of three out of 131 reported patients.

Comprehensive genotype-phenotype correlations between NLRP7 mutations and the balance between embryonic tissue differentiation and trophoblastic proliferation.

Background: Hydatidiform mole (HM) is a human pregnancy with excessive trophoblastic proliferation and abnormal embryonic development that may be sporadic or recurrent. In the sporadic form, the HM phenotype is driven by an abnormal ratio of paternal to maternal genomes, whereas in the recurrent form, the HM phenotype is caused by maternal-recessive mutations, mostly in NLRP7, despite the diploid biparental origin of the HM tissues. In this study, we characterised the expression of the imprinted, maternally expressed gene, CDKN1C (p57(KIP2)), the genotype, and the histopathology of 36 products of conception (POC) from patients with two defective alleles in NLRP7 and looked for potential correlations between the nature of the mutations in the patients and the various HM features.

Absence of KHDC3L mutations in Chinese patients with recurrent and sporadic hydatidiform moles.

To date, two maternal-effect genes have been shown to play causal roles in recurrent hydatidiform moles (RHMs). NLRP7, a major gene for this condition, codes for a nucleotide-binding oligomerization domain-like receptor and is mutated in 48 to 60% of patients with RHMs. KHDC3L is a recently identified gene that is mutated in 14% of NLRP7-negative patients.

Report of four new patients with protein-truncating mutations in C6orf221/KHDC3L and colocalization with NLRP7.

To date, two maternal-effect genes have been shown to have causative roles in recurrent hydatidiform moles (RHMs); NLRP7 that is mutated in 48-60% of patients with RHMs and C6orf221 (HUGO-approved nomenclature is now KHDC3L), a recently identified gene, that is mutated in 14% of patients with RHMs who are negative for NLRP7 mutations. We sequenced KHDC3L in 97 patients with RHMs and reproductive loss who are mostly negative for NLRP7 mutations. We identified three unrelated patients, each homozygous for one of the two protein-truncating mutations, a novel 4-bp deletion resulting in a frameshift, c.

Comparative ICE genomics: insights into the evolution of the SXT/R391 family of ICEs.

Integrating and conjugative elements (ICEs) are one of the three principal types of self-transmissible mobile genetic elements in bacteria. ICEs, like plasmids, transfer via conjugation; but unlike plasmids and similar to many phages, these elements integrate into and replicate along with the host chromosome. Members of the SXT/R391 family of ICEs have been isolated from several species of gram-negative bacteria, including Vibrio cholerae, the cause of cholera, where they have been important vectors for disseminating genes conferring resistance to antibiotics.