Differential Hox expression in murine embryonic stem cell models of normal and malignant hematopoiesis

The Hox family are master transcriptional regulators of developmental processes, including hematopoiesis. The Hox regulators, caudal homeobox factors (Cdx1-4), and Meis1, along with several individual Hox proteins, are implicated in stem cell expansion during embryonic development, with gene dosage playing a significant role in the overall function of the integrated Hox network. To investigate the role of this network in normal and aberrant, early hematopoiesis, we employed an in vitro embryonic stem cell differentiation system, which recapitulates mouse developmental hematopoiesis. Expression profiles of Hox, Pbx1, and Meis1 genes were quantified at distinct stages during the hematopoietic differentiation process and compared with the effects of expressing the leukemic oncogene Tel/PDGFR;2. During normal differentiation the Hoxa cluster, Pbx1 and Meis1 predominated, with a marked reduction in the majority of Hox genes (27/39) and Meis1 occurring during hematopoietic commitment. Only the posterior Hoxa cluster genes (a9, a10, a11, and a13) maintained or increased expression at the hematopoietic colony stage. Cdx4, Meis1, and a subset of Hox genes, including a7 and a9, were differentially expressed after short-term oncogenic (Tel/PDGFR;2) induction. Whereas Hoxa4-10, b1, b2, b4, and b9 were upregulated during oncogenic driven myelomonocytic differentiation. Heterodimers between Hoxa7/Hoxa9, Meis1, and Pbx have previously been implicated in regulating target genes involved in hematopoietic stem cell (HSC) expansion and leukemic progression. These results provide direct evidence that transcriptional flux through the Hox network occurs at very early stages during hematopoietic differentiation and validates embryonic stem cell models for gaining insights into the genetic regulation of normal and malignant hematopoiesis

Rehabilitating mangrove ecosystem services: a case study on the relative benefits of abandoned pond reversion from Panay Island, Philippines

Mangroves provide vital climate change mitigation and adaptation (CCMA) ecosystem services (ES), yet have suffered extensive tropics-wide declines. To mitigate losses, rehabilitation is high on the conservation agenda. However, the relative functionality and ES delivery of rehabilitated mangroves in different intertidal locations is rarely assessed. In a case study from Panay Island, Philippines, using field- and satellite-derived methods, we assess carbon stocks and coastal protection potential of rehabilitated low-intertidal seafront and mid- to upper-intertidal abandoned (leased) fishpond areas, against reference natural mangroves. Due to large sizes and appropriate site conditions, targeted abandoned fishpond reversion to former mangrove was found to be favourable for enhancing CCMA in the coastal zone. In a municipality-specific case study, 96.7% of abandoned fishponds with high potential for effective greenbelt rehabilitation had favourable tenure status for reversion. These findings have implications for coastal zone management in Asia in the face of climate change

A Method for Serial Tissue Processing and Parallel Analysis of Aberrant Crypt Morphology, Mucin Depletion, and Beta-Catenin Staining in an Experimental Model of Colon Carcinogenesis

The use of architectural and morphological characteristics of cells for establishing prognostic indicators by which individual pathologies are assigned grade and stage is a well-accepted practice. Advances in automated micro- and macroscopic image acquisition and digital image analysis have created new opportunities in the field of prognostic assessment; but, one area in experimental pathology, animal models for colon cancer, has not taken advantage of these opportunities. This situation is primarily due to the methods available to evaluate the colon of the rodent for the presence of premalignant and malignant pathologies. We report a new method for the excision and processing of the entire colon of the rat and illustrate how this procedure permitted the quantitative assessment of aberrant crypt foci (ACF), a premalignant colon pathology, for characteristics consistent with progression to malignancy. ACF were detected by methylene blue staining and subjected to quantitative morphometric analysis. Colons were then restained with high iron diamine–alcian blue for assessment of mucin depletion using an image overlay to associate morphometric data with mucin depletion. The subsequent evaluation of ACF for beta-catenin staining is also demonstrated. The methods described are particularly relevant to the screening of compounds for cancer chemopreventive activity

Here's looking at you, kid: attention to infant emotional faces in mothers and non-mothers.

Infant facial cues play a critical role in eliciting care and nurturance from an adult caregiver. Using an attentional capture paradigm we investigated attentional processing of adult and infant emotional facial expressions in a sample of mothers (n = 29) and non-mothers (n = 37) to determine whether infant faces were associated with greater task interference. Responses to infant target stimuli were slower than adult target stimuli in both groups. This effect was modulated by parental status, such that mothers compared to non-mothers showed longer response times to infant compared to adult faces. Both groups also responded more slowly to emotional faces, an effect that was more marked for infant emotional faces. Finally, it was found that greater levels of mothers' self-reported parental distress was associated with less task interference when processing infant faces. These findings indicate that for adult women, infant faces in general and emotional infant faces in particular, preferentially engage attention compared to adult faces. However, for mothers, infant faces appear to be more salient in general. Therefore, infant faces may constitute a special class of social stimuli. We suggest that alterations in attentional processing in motherhood may constitute an adaptive behavioural change associated with becoming a parent

New times, new politics: history and memory during the final years of the CPGB

This article examines the relationship between collective memory, historical interpretation and political identity. It focuses on the dissolution of the Communist Party of Great Britain (CPGB) as constructed through collective narrative memory, and on Marxist interpretations of history. The divisions within the party and the wider Marxist community, stretching from 1956 until 1991, were often framed around questions of historical interpretation. The events of 1989–1991 created an historical and mnemonic crisis for CPGB members who struggled to reconcile their past identities with their present situation. Unlike the outward-facing revisionism of other political parties, this was an intensely personal affair. The solution for many was to emphasise the need to find new ways to progress socialist aims, without relying on a discredited grand narrative. In contrast, other Communist parties, such as the Communist Party of Britain, which had been established (or ‘re-established’) in 1988, fared rather better. By adhering to the international party line of renewal and continued struggle, the party was able to hold its narrative together, condemning the excesses of totalitarian regimes, while reaffirming the need for international class struggle

Fetal Sex and RHD Genotyping with Digital PCR Demonstrates Greater Sensitivity than Real-time PCR.

BACKGROUND: Noninvasive genotyping of fetal RHD (Rh blood group, D antigen) can prevent the unnecessary administration of prophylactic anti-D to women carrying RHD-negative fetuses. We evaluated laboratory methods for such genotyping. METHODS: Blood samples were collected in EDTA tubes and Streck® Cell-Free DNA™ blood collection tubes (Streck BCTs) from RHD-negative women (n = 46). Using Y-specific and RHD-specific targets, we investigated variation in the cell-free fetal DNA (cffDNA) fraction and determined the sensitivity achieved for optimal and suboptimal samples with a novel Droplet Digital™ PCR (ddPCR) platform compared with real-time quantitative PCR (qPCR). RESULTS: The cffDNA fraction was significantly larger for samples collected in Streck BCTs compared with samples collected in EDTA tubes (P < 0.001). In samples expressing optimal cffDNA fractions (≥4%), both qPCR and digital PCR (dPCR) showed 100% sensitivity for the TSPY1 (testis-specific protein, Y-linked 1) and RHD7 (RHD exon 7) assays. Although dPCR also had 100% sensitivity for RHD5 (RHD exon 5), qPCR had reduced sensitivity (83%) for this target. For samples expressing suboptimal cffDNA fractions (<2%), dPCR achieved 100% sensitivity for all assays, whereas qPCR achieved 100% sensitivity only for the TSPY1 (multicopy target) assay. CONCLUSIONS: qPCR was not found to be an effective tool for RHD genotyping in suboptimal samples (<2% cffDNA). However, when testing the same suboptimal samples on the same day by dPCR, 100% sensitivity was achieved for both fetal sex determination and RHD genotyping. Use of dPCR for identification of fetal specific markers can reduce the occurrence of false-negative and inconclusive results, particularly when samples express high levels of background maternal cell-free DNA

Variability of Quasilinear Diffusion Coefficients for Plasmaspheric Hiss

In the outer radiation belt, the acceleration and loss of high‐energy electrons is largely controlled by wave‐particle interactions. Quasilinear diffusion coefficients are an efficient way to capture the small‐scale physics of wave‐particle interactions due to magnetospheric wave modes such as plasmaspheric hiss. The strength of quasilinear diffusion coefficients as a function of energy and pitch angle depends on both wave parameters and plasma parameters such as ambient magnetic field strength, plasma number density, and composition. For plasmaspheric hiss in the magnetosphere, observations indicate large variations in the wave intensity and wave normal angle, but less is known about the simultaneous variability of the magnetic field and number density. We use in situ measurements from the Van Allen Probe mission to demonstrate the variability of selected factors that control the size and shape of pitch angle diffusion coefficients: wave intensity, magnetic field strength, and electron number density. We then compare with the variability of diffusion coefficients calculated individually from colocated and simultaneous groups of measurements. We show that the distribution of the plasmaspheric hiss diffusion coefficients is highly non‐Gaussian with large variance and that the distributions themselves vary strongly across the three phase space bins studied. In most bins studied, the plasmaspheric hiss diffusion coefficients tend to increase with geomagnetic activity, but our results indicate that new approaches that include natural variability may yield improved parameterizations. We suggest methods like stochastic parameterization of wave‐particle interactions could use variability information to improve modeling of the outer radiation belt

The impact of surgery for vulval cancer upon health-related quality of life and pelvic floor outcomes during the first year of treatment: A longitudinal, mixed methods study

© 2015 The Authors.Objective: To measure the long-term impact of surgical treatment for vulval cancer upon health-related quality of life and pelvic floor outcomes during the first year of therapy. Methods: Prospective, longitudinal, mixed-methods study. Twenty-three women aged >18 years with a new diagnosis of vulval cancer were recruited. The EORTC QLQ C30, SF-36 and an electronic pelvic floor assessment questionnaire (ePAQ-PF) were administered at baseline (pre-treatment) and 3, 6, 9 and 12 months post-treatment. Mixed effects repeated measures models (all adjusted for age and BMI) were used to investigate changes over time and differences between cancer stage. Qualitative interviews were carried out with 11 of the women and analysed using a thematic approach. Results: Mean age was 59.9 years (SD=15.3; range=23.8-86.6 yrs). Mean BMI was 30.0 (SD=4.5; range=24.4-38.2). Sixteen women had early (Stage 1 to 2B), and seven women had advanced stage disease (Stage 3 to 4B). Questionnaire scores revealed that physical and social functioning, fatigue, pain and general sex life were significantly worse at 12 months than pre-treatment (p=< 0.05). Qualitative analysis revealed multiple treatment side effects which were perceived as severe and enduring. Women with advanced vulval cancer had significantly worse SF-36 mental health scores at 12 months compared to women with early stage disease (p=0.037). Conclusions: Surgery for vulval cancer has long-term implications which can be persistent 12 months post-treatment. High rates of morbidity relating to lymphoedema and sexual function re-enforce the need for specialist clinics to support women who suffer these complications

Histological analysis of low dose NMU effects in the rat mammary gland

<p>Abstract</p> <p>Background</p> <p>Our objective was to assess the histological changes in mammary glands of the female Wistar-Furth rat as a result of low dose exposure to N-nitrosomethylurea (NMU).</p> <p>Methods</p> <p>Groups of 30–40 virgin female rats of between 49–58 days old received a single injection of 10, 20, 30 or 50 mg NMU/kg body weight (BW). A group of 10 control rats received 0.9% NaCl solution only. The formation of palpable mammary gland tumors was assessed weekly and, upon sacrifice at 12, 22 and 25–30 weeks after treatment, we performed a comprehensive histological analysis of all mammary gland lesions and tumors.</p> <p>Results</p> <p>Alongside the predicted increase in tumor number and decrease in tumor latency with increasing NMU dose, we observed a number of microscopic lesions and other epithelial abnormalities in the mammary glands for all NMU doses. Two types of non-neoplastic histological changes were observed in rats exposed to 10 or 20 mg NMU/kg BW: namely, (i) an increase in the number of acinar structures often accompanied by secretion into the lumen which is normally associated with pregnancy and lactation, and (ii) an increase in the number of epithelial cells sloughed into the lumen of the epithelial ducts.</p> <p>Conclusion</p> <p>This study establishes a baseline for low-dose exposure and defines the histological features in the mammary gland resulting from NMU exposure. Furthermore, this system provides an ideal platform for evaluating the relative susceptibility of animals protected from, or predisposed to, developing cancer through environmental influences.</p