A standard of care for individuals with PIK3CA ‐related disorders: an international expert consensus statement

Growth promoting variants in PIK3CA cause a spectrum of developmental disorders, depending on the developmental timing of the mutation and tissues involved. These phenotypically heterogeneous entities have been grouped as PIK3CA-Related Overgrowth Spectrum disorders (PROS). Deep sequencing technologies have facilitated detection of low-level mosaic, often necessitating testing of tissues other than blood. Since clinical management practices vary considerably among healthcare professionals and services across different countries, a consensus on management guidelines is needed. Clinical heterogeneity within this spectrum leads to challenges in establishing management recommendations, which must be based on patient-specific considerations. Moreover, as most of these conditions are rare, affected families may lack access to the medical expertise that is needed to help address the multi-system and often complex medical issues seen with PROS. In March 2019, macrocephaly-capillary malformation (M-CM) patient organizations hosted an expert meeting in Manchester, United Kingdom, to help address these challenges with regards to M-CM syndrome. We have expanded the scope of this project to cover PROS and developed this consensus statement on the preferred approach for managing affected individuals based on our current knowledge

From Stimulus to Behavioral Decision-Making

International audienc

Runoff measurement methodology on vineyard plots in the mediterranean region

International audienc

Serine-threonine kinases and transcription factors active in signal transduction are detected at high levels of phosphorylation during mitosis in preimplantation embryos and trophoblast stem cells

Serine-threonine kinases and transcription factors play important roles in the G1-S phase progression of the cell cycle. Assays that use quantitative fluorescence by immunocytochemical means, or that measure band strength during Western blot analysis, may have confused interpretations if the intention is to measure G1-S phase commitment of a small subpopulation of phosphorylated proteins, when a larger conversion of the same population of proteins can occur during late G2 and M phases. In mouse trophoblast stem cells (TSC), a human placental cell line (HTR), and/or mouse preimplantation embryos, 8/19 serine-threonine and tyrosine kinases, 3/8 transcription factors, and 8/14 phospho substrate and miscellaneous proteins were phosphorylated at higher levels in M phase than in interphase. Most phosphoproteins appeared to associate with the spindle complex during M phase, but one (p38MAPK) associated with the spindle pole and five (Cdx2, MEK1, 2, p27, and RSK1) associated with the DNA. Phosphorylation was detected throughout apparent metaphase, anaphase and telophase for some proteins, or for only one of these segments for others. The phosphorylation was from 2.1- to 6.2-fold higher during M phase compared with interphase. These data suggest that, when planning and interpreting quantitative data and perturbation experiments, consideration must be given to the role of serine-threonine kinases and transcription factors during decision making in M phase as well as in G1-S phase

Spark plasma sintering of commercial alumina powder and comparison with hot pressing

International audienc