Magnetic resonance imaging in the prenatal diagnosis of neural tube defects

OBJECTIVE: To assess the role of magnetic resonance imaging (MRI) in the prenatal diagnosis of neural tube defects (NTDs). BACKGROUND: NTDs comprise a heterogeneous group of congenital anomalies that derive from the failure of the neural tube to close. Advances in ultrasonography and MRI have considerably improved the diagnosis and treatment of NTDs both before and after birth. Ultrasonography is the first technique in the morphological study of the fetus, and it often makes it possible to detect or suspect NTDs. Fetal MRI is a complementary technique that makes it possible to clear up uncertain ultrasonographic findings and to detect associated anomalies that might go undetected at ultrasonography. The progressive incorporation of intrauterine treatments makes an accurate diagnosis of NTDs essential to ensure optimal perinatal management. The ability of fetal MRI to detect complex anomalies that affect different organs has been widely reported, and it can be undertaken whenever NTDs are suspected. CONCLUSION: We describe the normal appearance of fetal neural tube on MRI, and we discuss the most common anomalies involving the structures and the role of fetal MRI in their assessment. KEY POINTS: • To learn about the normal anatomy of the neural tube on MRI • To recognise the MR appearance of neural tube defects • To understand the value of MRI in assessing NTD

Dose Dependent Effects on Cell Cycle Checkpoints and DNA Repair by Bendamustine

Bendamustine (BDM) is an active chemotherapeutic agent approved in the U. S. for treating chronic lymphocytic leukemia and non-Hodgkin lymphoma. Its chemical structure suggests it may have alkylator and anti-metabolite activities; however the precise mechanism of action is not well understood. Here we report the concentration-dependent effects of BDM on cell cycle, DNA damage, checkpoint response and cell death in HeLa cells. Low concentrations of BDM transiently arrested cells in G2, while a 4-fold higher concentration arrested cells in S phase. DNA damage at 50, but not 200 µM, was efficiently repaired after 48 h treatment, suggesting a difference in DNA repair efficiency at the two concentrations. Indeed, perturbing base-excision repair sensitized cells to lower concentrations of BDM. Timelapse studies of the checkpoint response to BDM showed that inhibiting Chk1 caused both the S- and G2-arrested cells to prematurely enter mitosis. However, whereas the cells arrested in G2 (low dose BDM) entered mitosis, segregated their chromosomes and divided normally, the S-phase arrested cells (high dose BDM) exhibited a highly aberrant mitosis, whereby EM images showed highly fragmented chromosomes. The vast majority of these cells died without ever exiting mitosis. Inhibiting the Chk1-dependent DNA damage checkpoint accelerated the time of killing by BDM. Our studies suggest that BDM may affect different biological processes depending on drug concentration. Sensitizing cells to killing by BDM can be achieved by inhibiting base-excision repair or disrupting the DNA damage checkpoint pathway

Climate-induced changes in grapevine yield and must sugar content in Franconia (Germany) between 1805 and 2010

When attempting to estimate the impacts of future climate change it is important to reflect on information gathered during the past. Understanding historical trends may also aid in the assessment of likely future agricultural and horticultural changes. The timing of agricultural activities, such as grape harvest dates, is known to be influenced by climate and weather. However, fewer studies have been carried out on grapevine yield and quality. In this paper an analysis is undertaken of long-term data from the period 1805-2010 on grapevine yield (hl/ha) and must sugar content (°Oe) and their relation to temperature. Monthly mean temperatures were obtained for the same time period. Multiple regression was used to relate the viticulture variables to temperature, and long-term trends were calculated. Overall, the observed trends over time are compatible with results from other long term studies. The findings confirm a relationship between yield, must sugar content and temperature data; increased temperatures were associated with higher yields and higher must sugar content. However, the potential increase in yield is currently limited by legislation, while must sugar content is likely to further increase with rising temperatures

Genomic and functional regulation of TRIB1 contributes to prostate cancer pathogenesis

Prostate cancer is the most frequent malignancy in European men and the second worldwide. One of the major oncogenic events in this disease includes amplification of the transcription factor cMYC. Amplification of this oncogene in chromosome 8q24 occurs concomitantly with the copy number increase in a subset of neighboring genes and regulatory elements, but their contribution to disease pathogenesis is poorly understood. Here we show that TRIB1 is among the most robustly upregulated coding genes within the 8q24 amplicon in prostate cancer. Moreover, we demonstrate that TRIB1 amplification and overexpression are frequent in this tumor type. Importantly, we find that, parallel to its amplification, TRIB1 transcription is controlled by cMYC. Mouse modeling and functional analysis revealed that aberrant TRIB1 expression is causal to prostate cancer pathogenesis. In sum, we provide unprecedented evidence for the regulation and function of TRIB1 in prostate cancer