Flux compactifications and supersymmetry breaking in 6D gauged supergravity

We review on a recent construction of the on-shell supersymmetric brane action for the codimension-two branes with nonzero tension in the flux compactification of a 6D chiral gauged supergravity. On dimesionally reducing on 4D gauged supergravity for a new supersymmetric unwarped background with conical branes, we consider the modulus stabilization for determining the soft masses of the scalars localized on the branes and show that the bulk U(1)_R provides a new mechanism for mediating the SUSY breaking.Comment: 12 pages, no figures, Invited review for Modern Physics Letters A, Published versio

TBX5 and NuRD Divide the Heart

In this issue of Developmental Cell, Waldron et al. (2016) identify an interaction between a master regulator of heart development, TBX5, and the NuRD complex and describe how mutations affecting the interaction may contribute to congenital heart disease. Furthermore, these interactions may have contributed to the evolution of cardiac septation

Fluorescence-enhanced surgical navigation : towards tailored tumor detection

Fluorescence imaging is a technique that can be used to selectively highlight certain structures during surgery. This includes structures that need to be spared (bile ducts, ureters) as well as structures that need to be resected (tumor tissue, sentinel lymph nodes). During the last decades, the focus has shifted towards development and clinical testing of novel tutor-specific fluorescent tracers. This thesis first focuses on exploring indications of fluorescence-guidance during HPB surgery. Subsequently, novel tutor-targeted tracers are tested in preclinical studies and tailored tumor detection is evaluated. Finally, clinical studies with novel tutor-targeted tracers are presented.CHDRLUMC / Geneeskund

Manganese-oxidizing bacteria mediate the degradation of 17α-ethinylestradiol

Manganese (II) and manganese-oxidizing bacteria were used as an efficient biological system for the degradation of the xenoestrogen 17 alpha-ethinylestradiol (EE2) at trace concentrations. Mn(2+)-derived higher oxidation states of Mn (Mn(3+), Mn(4+)) by Mn(2+)-oxidizing bacteria mediate the oxidative cleavage of the polycyclic target compound EE2. The presence of manganese (II) was found to be essential for the degradation of EE2 by Leptothrix discophora, Pseudomonas putida MB1, P. putida MB6 and P. putida MB29. Mn(2+)-dependent degradation of EE2 was found to be a slow process, which requires multi-fold excess of Mn(2+) and occurs in the late stationary phase of growth, implying a chemical process taking place. EE2-derived degradation products were shown to no longer exhibit undesirable estrogenic activity

Tbx20 Is Required in Mid-Gestation Cardiomyocytes and Plays a Central Role in Atrial Development.

RationaleMutations in the transcription factor TBX20 (T-box 20) are associated with congenital heart disease. Germline ablation of Tbx20 results in abnormal heart development and embryonic lethality by embryonic day 9.5. Because Tbx20 is expressed in multiple cell lineages required for myocardial development, including pharyngeal endoderm, cardiogenic mesoderm, endocardium, and myocardium, the cell type-specific requirement for TBX20 in early myocardial development remains to be explored.ObjectiveHere, we investigated roles of TBX20 in midgestation cardiomyocytes for heart development.Methods and resultsAblation of Tbx20 from developing cardiomyocytes using a doxycycline inducible cTnTCre transgene led to embryonic lethality. The circumference of developing ventricular and atrial chambers, and in particular that of prospective left atrium, was significantly reduced in Tbx20 conditional knockout mutants. Cell cycle analysis demonstrated reduced proliferation of Tbx20 mutant cardiomyocytes and their arrest at the G1-S phase transition. Genome-wide transcriptome analysis of mutant cardiomyocytes revealed differential expression of multiple genes critical for cell cycle regulation. Moreover, atrial and ventricular gene programs seemed to be aberrantly regulated. Putative direct TBX20 targets were identified using TBX20 ChIP-Seq (chromatin immunoprecipitation with high throughput sequencing) from embryonic heart and included key cell cycle genes and atrial and ventricular specific genes. Notably, TBX20 bound a conserved enhancer for a gene key to atrial development and identity, COUP-TFII/Nr2f2 (chicken ovalbumin upstream promoter transcription factor 2/nuclear receptor subfamily 2, group F, member 2). This enhancer interacted with the NR2F2 promoter in human cardiomyocytes and conferred atrial specific gene expression in a transgenic mouse in a TBX20-dependent manner.ConclusionsMyocardial TBX20 directly regulates a subset of genes required for fetal cardiomyocyte proliferation, including those required for the G1-S transition. TBX20 also directly downregulates progenitor-specific genes and, in addition to regulating genes that specify chamber versus nonchamber myocardium, directly activates genes required for establishment or maintenance of atrial and ventricular identity. TBX20 plays a previously unappreciated key role in atrial development through direct regulation of an evolutionarily conserved COUPT-FII enhancer

Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy

Purpose: Adjuvant chemotherapy for breast cancer can have adverse effects on cognition shortly after administration. Whether chemotherapy has any long-term effects on cognition is largely unknown, yet it becomes increasingly relevant because of the widespread use of chemotherapy for early-stage breast cancer and the improved survival. We investigated whether cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy for breast cancer is associated with worse cognitive performance more than 20 years after treatment. Patients and Methods: This case-cohort study compared the cognitive performance of patients with breast cancer who had a history of adjuvant CMF chemotherapy treatment (six cycles; average time since treatment, 21 years; n = 196) to that of a population-based sample of women never diagnosed with cancer (n = 1,509). Participants were between 50 and 80 years of age. Exclusion criteria were ever use of adjuvant endocrine therapy, secondary malignancy, recurrence, and/or metastasis. Results: The women exposed to chemotherapy performed significantly worse than the reference group on cognitive tests of immediate (P = .015) and delayed verbal memory (P = .002), processing speed (P < .001), executive functioning (P = .013), and psychomotor speed (P = .001). They experienced fewer symptoms of depression (P < .001), yet had significantly more memory complaints on two of three measures that could not be explained by cognitive test performance. Conclusion: Survivors of breast cancer treated with adjuvant CMF chemotherapy more than 20 years ago perform worse, on average, than random population controls on neuropsychological tests. The pattern of cognitive problems is largely similar to that observed in patients shortly after cessation of chemotherapy. This study suggests that cognitive deficits following breast cancer diagnosis and subsequent CMF chemotherapy can be long lasting