Endoscopic placental laser coagulation in dichorionic and monochorionic triplet pregnancies

Objective: To report outcome of monochorionic (MC) and dichorionic (DC) triamniotic (TA) triplet pregnancies treated with endoscopic laser coagulation of communicating placental vessels for severe fetofetal transfusion syndrome (FFTS) and selective fetal growth restriction (sFGR). Methods: Laser surgery was performed at 18 (15-24) weeks gestation in 11 MCTA and 33 DCTA pregnancies complicated by FFTS and 14 DCTA pregnancies complicated by sFGR. Data from our study and previous reports were pooled using meta-analytic techniques. Results: Survival of at least one baby and survival among all fetuses was 97.0% and 72.7% in DCTA pregnancies with FFTS, 78.6% and 52.4% in DCTA pregnancies with sFGR and 81.8% and 39.4% in MCTA pregnancies with FFTS. In the combined data from our study and previous reports, the pooled survival rates in 132 DCTA pregnancies with FFTS were 94.4% and 76.1% and in 29 MCTA pregnancies with FFTS were 80.6% and 57.5%. Conclusions: Survival after laser surgery is higher in DC triplets with FFTS than those with sFGR and in DC than MC triplets with FFTS

A simple remark on a flat projective morphism with a Calabi-Yau fiber

If a K3 surface is a fiber of a flat projective morphisms over a connected noetherian scheme over the complex number field, then any smooth connected fiber is also a K3 surface. Observing this, Professor Nam-Hoon Lee asked if the same is true for higher dimensional Calabi-Yau fibers. We shall give an explicit negative answer to his question as well as a proof of his initial observation.Comment: 8 pages, main theorem is generalized, one more remark is added, mis-calculation and typos are corrected etc

Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

<p>Abstract</p> <p>Background</p> <p>Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID) mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL). However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential.</p> <p>Results</p> <p>Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel <it>in silico </it>and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation.</p> <p>Conclusions</p> <p>We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy <it>in vivo</it>.</p

The fate of oxidative strand breaks in mitochondrial DNA

Mitochondrial DNA (mtDNA) is particularly vulnerable to somatic mutagenesis. Potential mechanisms include DNA polymerase γ (POLG) errors and the effects of mutagens, such as reactive oxygen species. Here, we studied the effects of transient hydrogen peroxide (H(2)O(2) pulse) on mtDNA integrity in cultured HEK 293 cells, applying Southern blotting, ultra-deep short-read and long-read sequencing. In wild-type cells, 30 min after the H(2)O(2) pulse, linear mtDNA fragments appear, representing double-strand breaks (DSB) with ends characterized by short GC stretches. Intact supercoiled mtDNA species reappear within 2–6 h after treatment and are almost completely recovered after 24 h. BrdU incorporation is lower in H(2)O(2)-treated cells compared to non-treated cells, suggesting that fast recovery is not associated with mtDNA replication, but is driven by rapid repair of single-strand breaks (SSBs) and degradation of DSB-generated linear fragments. Genetic inactivation of mtDNA degradation in exonuclease deficient POLG p.D274A mutant cells results in the persistence of linear mtDNA fragments with no impact on the repair of SSBs. In conclusion, our data highlight the interplay between the rapid processes of SSB repair and DSB degradation and the much slower mtDNA re-synthesis after oxidative damage, which has important implications for mtDNA quality control and the potential generation of somatic mtDNA deletions

Betti numbers for numerical semigroup rings

We survey results related to the magnitude of the Betti numbers of numerical semigroup rings and of their tangent cones.Comment: 22 pages; v2: updated references. To appear in Multigraded Algebra and Applications (V. Ene, E. Miller Eds.

Estrogen directly activates AID transcription and function

The immunological targets of estrogen at the molecular, humoral, and cellular level have been well documented, as has estrogen's role in establishing a gender bias in autoimmunity and cancer. During a healthy immune response, activation-induced deaminase (AID) deaminates cytosines at immunoglobulin (Ig) loci, initiating somatic hypermutation (SHM) and class switch recombination (CSR). Protein levels of nuclear AID are tightly controlled, as unregulated expression can lead to alterations in the immune response. Furthermore, hyperactivation of AID outside the immune system leads to oncogenesis. Here, we demonstrate that the estrogen–estrogen receptor complex binds to the AID promoter, enhancing AID messenger RNA expression, leading to a direct increase in AID protein production and alterations in SHM and CSR at the Ig locus. Enhanced translocations of the c-myc oncogene showed that the genotoxicity of estrogen via AID production was not limited to the Ig locus. Outside of the immune system (e.g., breast and ovaries), estrogen induced AID expression by >20-fold. The estrogen response was also partially conserved within the DNA deaminase family (APOBEC3B, -3F, and -3G), and could be inhibited by tamoxifen, an estrogen antagonist. We therefore suggest that estrogen-induced autoimmunity and oncogenesis may be derived through AID-dependent DNA instability