Early steps in neural induction

Neural induction is the instructive interaction whereby signals emitted from the organizer direct cells in the ectoderm to a neural fate and thereby to form the neural plate. Recent work in many labs has suggested that it involves a hierarchy of molecular events. Here, I investigate the earliest steps in the neural induction cascade and the signals that define them. Many genes expressed during the neural induction cascade have been shown to be regulated by FGF. However the signals that induce three of the genes, Bert, TrkC and Obelix, are unknown. I therefore tested candidate signalling molecules by misexpression analysis. While Obelix is also regulated by FGF, none of many factors tested, including FGF, retinoic acid, somatostatin, noggin, insulin, and increasing intracellular calcium were able to induce expression of TrkC or Bert. BMP also plays an important role in neural induction, I therefore studied how cells may integrate TGFβ signalling through Smad1 and Smad2. I used a BiFCo approach to investigate Smad protein binding interactions in culture and in vivo, however this did not turn out to be a useful method for this question. Finally I investigated the ground-state of the epiblast at the start of the neural induction cascade. Culture of early epiblast explants showed, unexpectedly, that cells initially enter a state similar to that of the neural plate border, confirmed by their subsequent differentiation into lens. This correlates with the finding that BMP signalling in vivo only affects cells of the neural plate border region and suggests why explants can be neuralized by BMP. Overall, the experiments reveal a hitherto unknown importance of a neural border cell-state, and suggest that lens is the ground state at the start of the neural induction cascade

A Rare Cause of Scrotal Swelling: Transitional Cell Carcinoma of the Bladder Presenting as a Testicular Metastasis

A 72-year-old Caucasian male who presented with haematuria in July of 2000 was found to have a large left-sided bladder tumour. He underwent a transurethral resection of the tumour and surveillance program. In October 2008 he underwent a transurethral resection of the prostate (TURP). Histology of the prostatic chippings showed poorly differentiated TCC with prostatic invasion. A CT of his chest abdomen and pelvis revealed no lymph node involvement or metastatic spread. He therefore underwent a cystoprostato-urethrectomy with ileal conduit formation, in December 2008. In May 2010 the decision was made to perform a left inguinal orchidectomy as he presented with a craggy mass of his left testis, and there were clinical concerns that this was a tumour. Histology revealed that the left testis had been wholly replaced by a tumour. Taking into account his previous urological history, the features of this tumour are consistent with metastatic TCC, which is very rare

The effect of pumping water from wells in an aquifer

Groundwater is sensitive to the climate change and agricultural activities in arid and semi-arid areas. Over the past several decades, human activities, such as groundwater extraction for irrigation, have resulted in aquifer overdraft and disrupted the natural equilibrium in these areas. This study reports research on the effect of pumping water from several wells in a given aquifer. We have considered, for simplicity, an idealized one layer aquifer which has been discretized into 49 identical blocks studied on the middle horizontal row of blocks. We have developed a numerical simulating model by discretizing the equation of continuity which we have converted into computer codes. A program has then been written. This program has successfully generated both hydraulic head and velocity profile distributions. The results reveal that there are less hydraulic head losses on pumpage from blocks which are far apart, the velocities being least in blocks which are far from the pumpage blocks. The results obtained have a high correlation with those from the well-known Theis equation for drawdown. The results would greatly help in limiting the usage of a given aquifer with respect to the maximum number of wells permissible in the aquifer as well as predict the levels of groundwater in a particular aquifer.Key words: Aquifer, piezometric height, velocity profiles and simulatio

In vitro modelling of epithelial and stromal interactions in non-malignant and malignant prostates

To study the effects of stromal epithelial cell interactions on prostate cancer metastasis, we have used primary human prostatic stromal cells derived from malignant and non-malignant tissues and established epithelial cell lines from normal (PNT1a and PNT2-C2) and tumour (PC-3, DU145 and LNCaP) origins. The effects of stromal cells on epithelial cell growth were studied in direct and indirect (using culture inserts) co-culture and by exposure to stromal cell-conditioned medium (assessed by MTT assay). The influence of stromal cells on epithelial cell invasion was measured using matrigel invasion chambers and on epithelial cell motility using time lapse microscopy. Results indicated that epithelial cell line growth was similarly unaffected or inhibited by stromal cells derived from malignant (n = 8) or non-malignant tissue (n = 8). In contrast, PNT2-C2 and PC-3 cells were found to be the least and the most invasive and motile epithelia respectively. Stromal cultures enhanced the invasion of both epithelial cells, but no differences were observed between the use of malignant and non-malignant tissues. All stromal cultures modestly stimulated PNT2-C2 motility but displayed a greater stimulation of PC-3 cell motility, while stromal cells derived from malignant tissue stimulated PNT2-C2 and PC-3 cell motility more than stromal cultures from non-malignant tissues. © 2000 Cancer Research Campaig

Understanding challenging behaviour as a social construction: exploring the role of pupil-teacher discourse in the secondary classroom

Challenging behaviour continues to be portrayed by the media, politicians and educationalist as a cause for concerns in UK secondary schools (DfE 2015, NASUWT, 2014). In recent years, there has been a shift in thinking amongst some researchers (Graff, 2009, Pomerantz, 2005) about how to view challenging behaviour in the classroom, recognising its idiographic nature. By drawing upon other disciplines, alongside psychology, social constructionist thinking has emerged as a helpful position from which to view challenging behaviour. From this position, challenging behaviour is socially constructed through language and action in the classroom. This study explored challenging verbal behaviour in the secondary classroom from a social constructionist perspective. A series of observations of three Key Stage 3 pupils and their teachers were completed. These observations were supported by audio-recording and qualitative observation records. To analyse the data, two approaches to Discourse Analysis, namely Conversation Analysis and Critical Discourse Analysis, were used to explore pupil-teacher interaction. This analysis focused on the ways micro and macro features of classroom talk created potential for the construction of challenging verbal behaviour. The institutionally defined asymmetry in pupil-teacher roles impacted upon the range and use of linguistic devices used by teachers and pupils. Teachers used a broader range of sophisticated strategies to maintain their authority control of the discourse. Pupils would then seek to address this asymmetry through talk, sometimes impulsively, leading to the construction of situations related to behaviour. As such, challenging verbal behaviour emerged when there was conflict between the pupil and teacher roles in the interactional space in the classroom. This study has several implications for the practice of Educational Psychologists and teachers. It highlighted the importance of considering the micro-level features of pupil-teacher talk in the classroom, recognising their idiographic nature. Dominant discourses, power and institutional talk can make certain things ‘thinkable’ and ‘sayable’ therefore highlighting the importance of reflexivity and criticality around the language that is used when talking about challenging behaviour. Finally, the potential value of Discourse Analysis and social constructionist thinking in understanding challenging behaviour was also identified as a possible way forward, both for the evidence base and for practice

Understanding challenging behaviour as a social construction: exploring the role of pupil-teacher discourse in the secondary classroom

Challenging behaviour continues to be portrayed by the media, politicians and educationalist as a cause for concerns in UK secondary schools (DfE 2015, NASUWT, 2014). In recent years, there has been a shift in thinking amongst some researchers (Graff, 2009, Pomerantz, 2005) about how to view challenging behaviour in the classroom, recognising its idiographic nature. By drawing upon other disciplines, alongside psychology, social constructionist thinking has emerged as a helpful position from which to view challenging behaviour. From this position, challenging behaviour is socially constructed through language and action in the classroom. This study explored challenging verbal behaviour in the secondary classroom from a social constructionist perspective. A series of observations of three Key Stage 3 pupils and their teachers were completed. These observations were supported by audio-recording and qualitative observation records. To analyse the data, two approaches to Discourse Analysis, namely Conversation Analysis and Critical Discourse Analysis, were used to explore pupil-teacher interaction. This analysis focused on the ways micro and macro features of classroom talk created potential for the construction of challenging verbal behaviour. The institutionally defined asymmetry in pupil-teacher roles impacted upon the range and use of linguistic devices used by teachers and pupils. Teachers used a broader range of sophisticated strategies to maintain their authority control of the discourse. Pupils would then seek to address this asymmetry through talk, sometimes impulsively, leading to the construction of situations related to behaviour. As such, challenging verbal behaviour emerged when there was conflict between the pupil and teacher roles in the interactional space in the classroom. This study has several implications for the practice of Educational Psychologists and teachers. It highlighted the importance of considering the micro-level features of pupil-teacher talk in the classroom, recognising their idiographic nature. Dominant discourses, power and institutional talk can make certain things ‘thinkable’ and ‘sayable’ therefore highlighting the importance of reflexivity and criticality around the language that is used when talking about challenging behaviour. Finally, the potential value of Discourse Analysis and social constructionist thinking in understanding challenging behaviour was also identified as a possible way forward, both for the evidence base and for practice