Marion Blumenstein

UDP-glucuronosyltransferase activity, expression and cellular localization in human placenta at term

The activity, expression and localization of the UDP-glucuronosyltransferases (UGTs) were investigated in human placenta at term. UGT activity (measured with the substrate 4-methylumbelliferone (4-MU)) was observed in all 25 placentas sampled and maximum velocity (V(max)) ranged 13-fold from 5.1+/-0.9 to 66.9+/-17.5 nmol/min/mg protein (mean+/-SD). Substrate affinity (K(m)) ranged 5-fold from 246+/-24 to 1124+/-422 microM. Using reverse transcriptase-polymerase chain reaction (RT-PCR), expression of the isoforms UGT2B4, 2B7, 2B10, 2B11 and 2B15 was observed in all (12/12) placentas sampled and expression of UGT2B17 was noted in 8/12 placentas. Northern analysis of the UGT2B7 isoform in 12 placentas revealed a 10-fold difference in expression with RT-PCR variability and the 13-fold variation observed in UGT activity. The presence of UGT2B4 and 2B7 proteins (52 and 56kDa, respectively) was demonstrated by Western blotting. The sites of placental UGT2B transcription (in situ hybridization) and protein expression (immunohistochemistry) were located in the syncytium of the placental trophoblasts bordering the placental villi. UGT1A proteins could not be observed with immunohistochemistry or Western blotting and expression could not be observed with RT-PCR. Our discovery of UGT expression and activity at the site of maternal-fetal exchange is consistent with a role for UGTs in detoxification of exogenous and endogenous ligands and the maintenance of placental function through clearance and regulation of steroid hormones.

A proteomic approach identifies early pregnancy biomarkers for preeclampsia: Novel linkages between a predisposition to preeclampsia and cardiovascular disease

Preeclampsia (PE) is a common, potentially life‐threatening pregnancy syndrome triggered by placental factors released into the maternal circulation, resulting in maternal vascular dysfunction along with activated inflammation and coagulation. Currently there is no screening test for PE. We sought to identify differentially expressed plasma proteins in women who subsequently develop PE that may perform as predictive biomarkers. In seven DIGE experiments, we compared the plasma proteome at 20 wk gestation in women who later developed PE with an appropriate birth weight for gestational age baby (n=27) or a small for gestational age baby (n=12) to healthy controls with uncomplicated pregnancies (n=57). Of the 49 differentially expressed spots associated with PE‐appropriate for gestational age, PE‐small for gestational age or both (p<0.05, false discovery rate corrected), 39 were identified by LC‐MS/MS. Two protein clusters that accurately (>90%) classified women at risk of developing PE were identified. Immunoblots confirmed the overexpression of fibrinogen γ chain and α‐1‐antichymotrypsin in plasma prior to PE. The proteins identified are involved in lipid metabolism, coagulation, complement regulation, extracellular matrix remodeling, protease inhibitor activity and acute‐phase responses, indicating novel synergism between pathways involved in the pathogenesis of PE. Our findings are remarkably similar to recently identified proteins complexed to high‐density lipoprotein and linked to cardiovascular disease.

Different for women? The challenges of doctoral studies

This exploratory study investigates gender-specific differences in the challenges of the doctoral experience through the observations of a counsellor working with doctoral students. The article first contextualises the study within the literature investigating doctoral attrition and gender equity, showing that identity transformation over the doctorate is problematic in particular aspects for women. We confirm that cultural expectations regarding women passivity, family nurturance and (at least symbolic) subordination to male authority can cause tensions between womens social relationships and academic performance which values assertiveness, clear communication and confident management of power relationships. We identify various conflicts between the female roles of the social sphere and the academic arena that problematise the identity transition of the doctorate from student to independent researcher.

Aberrant Processing of Plasma Vitronectin and High-Molecular-Weight Kininogen Precedes the Onset of Preeclampsia

To date, there is no reliable test to identify women in early pregnancy at risk of developing preeclampsia. Difference gel electrophoresis (DIGE) identified the plasma proteins vitronectin (VN) and high-molecular-weight kininogen (HK) in association with preeclampsia. In a longitudinal proteomics study, the plasma of preeclamptic patients (n = 6) was compared to healthy control participants (n = 6) before the onset of preeclampsia (week 20) and at the time of presentation with clinical disease (weeks 33-36). The 75-kd single-chain VN molecule increased 1.6- to 1.9-fold in preeclampsia, whereas the 65-kd moiety of the 2-chain VN molecule decreased 1.5- to 1.7-fold compared to healthy controls (P < .05). Immunoblots revealed differences in proteolytic processing of VN and/or HK in women who develop preeclampsia or preeclampsia further complicated by small-for-gestational-age. Vitronectin and HK may prove to be useful as early markers of fibrinolytic activity and neutrophil activation, which are known to be associated with preeclampsia.

Plasma clusterin increased prior to Small for Gestational Age (SGA) associated with preeclampsia and decreased prior to SGA in normotensive pregnancies

In our search for early biomarkers for the pregnancy complicationssmall for gestational age (SGA) and preeclampsia (PE) we analysed plasma from 19-21 weeks gestation in women recruited into the SCOPE study, a prospective cohort of nulliparous women, by differential in gel electrophoresis (DIGE). DIGE revealed the differential expression of clusterin levels and its isoforms in top6-depleted plasma of women who delivered an SGA infant but remained normotensive (SGA-NT; N = 8) compared to healthy women with an uncomplicated pregnancy outcome (Controls, N = 8). Immunosorbent enzyme-linked assay (ELISA) showed that compared to plasma clusterin levels from healthy controls [71.1 (SD 12.4) µg/mL, n = 39], clusterin was decreased in SGA-NT [58.3 (SD 11.7), N = 20, P < 0.0001], increased in women with SGA and PE [81.5 (SD 14.8), N = 20, P < 0.01], but similar in PE alone [71.2 (SD 9.4)g/ml, P = 1.0]. Screening for clusterin levels and/or its different isoformsmay be useful in mid-pregnancy to identify women who subsequently develop SGA but remain normotensive or who develop preeclampsia with SGA.

Seven Ways of Looking at a Data Set

A literary theorist, a biologist, an historian, a writing studies scholar, and a poet walk into a wine bar. The poet says, “I’ve got a stack of 1,223 handwritten questionnaire responses here in my bag; would you like to have a look?” The others reply, “Sure. Let’s see what we can learn here.” Descending from their respective disciplinary perches, they all gather around a table and start sifting through the questionnaires, which chronicle the writing background, habits, and emotions of PhD students and faculty in 15 countries. In this single corpus of data, each researcher sees something different, and from the other researchers’ responses, each learns new ways of seeing. What counts as an appropriate data analysis? What, for that matter, counts as data? We invite you to grab a drink and join our conversation.

The generic-discipline dilemma: learning advising in quantitative literacy

– This paper aims to provide insights into the experiences of and challenges confronting higher degree research students and learning advisors (LAs) regarding data analysis support. The ability to handle data and use numerical evidence systematically is an important transferable skill and essential for the successful completion of a quantitative research thesis. , – A combination of qualitative and quantitative data was used, enabling a convergence of findings: the questionnaire and one-on-one advisory sessions feedback gathered information on the student experience, while semi-structured interviews provided data on the LAs’ perspective. , – Phenomenographic analysis of interviews revealed many challenges associated with centralised learning support provision. Learning advisors recognised not only different disciplinary needs but also the tensions associated with working centrally and cross-disciplinary. Students identified a need for more practice-orientated training opportunities in data analysis during their postgraduate and doctoral research. , – Understanding gained from students’ and LAs’ experiences are essential for changes of university-wide teaching and learning strategies. The collection of “bottom-up” data on the student experience combined with data on learning thresholds provided by faculty and student learning support units would allow a coordinated, institution-wide approach to identified learning needs. , – Developing a community of practice concerned with quantitative literacy means that staff with expert knowledge, regardless of discipline affiliation, can provide an environment in which students are able to develop their analytical skills further and can participate in ongoing discussions on real-life research and data analysis issues.