Wound healing in the liver with particular reference to stem cells

The efficiency of liver regeneration in response to the loss of hepatocytes is widely acknowledged, and this is usually accomplished by the triggering of normally proliferatively quiescent hepatocytes into the cell cycle. However, when regeneration is defective, tortuous ductular structures, initially continuous with the biliary tree, proliferate and migrate into the surrounding hepatocyte parenchyma. In humans, these biliary cells have variously been referred to as ductular structures, neoductules and neocholangioles, and have been observed in many forms of chronic liver disease, including cancer. In experimental animals, similar ductal cells are usually called oval cells, and their association with impaired regeneration has led to the conclusion that they are the progeny of facultative stem cells. Oval cells are of considerable biological interest as they may represent a target population for hepatic carcinogens, and they may also be useful vehicles for ex vivo gene therapy for the correction of inborn errors of metabolism. This review proposes that the liver harbours stem cells that are located in the biliary epithelium, that oval cells are the progeny of these stem cells, and that these cells can undergo massive expansion in their numbers before differentiating into hepatocytes. This is a conditional process that only occurs when the regenerative capacity of hepatocytes is overwhelmed, and thus, unlike the intestinal epithelium, the liver is not behaving as a classical, continually renewing, stem cell-fed lineage. We focus on the biliary network, not merely as a conduit for bile, but also as a cell compartment with the ability to proliferate under appropriate conditions and give rise to fully differentiated hepatocytes and other cell types.     

Proliferating cell nuclear antigen (PCNA) immunostaining--a prognostic factor in ovarian cancer?

The measurement of tumour cell proliferation is becoming increasingly recognised in defining prognostic groups. Proliferating cell nuclear antigen (PCNA) immunolocalisation can be used as an index of cell proliferation and may define the extent of departure from normal growth control. The monoclonal antibody PC10 stains PCNA in archival paraffin-embedded tissue. This study investigates its potential as a prognostic marker in early and advanced ovarian cancer. A three-stage immunoperoxidase technique was developed to detect the monoclonal antibody PC10. Archival paraffin-embedded tissue from 19 stage I ovarian tumours (13 malignant and six borderline) and 79 advanced (stage IIb-IV) ovarian tumours (patients entered into the Third North-West Thames Ovarian Cancer Trial) was immunostained with PC10. PC10 immunostaining was performed successfully in 91.8% of cases. The PC10 labelling index (PC10 LI) ranged from 1.5% to 88% with a mean value of 47.4%. Stage I borderline tumours had significantly lower PCNA labelling indexes than stage I malignant tumours (P < 0.048). In advanced disease there was an inverse correlation between PC10 and overall survival, and in those patients who underwent good debulking surgery (37 patients with disease < 2 cm diameter) a low PC10 value (< 36.5%) correlated with improved survival (log-rank trend test for survival, chi 2 = 5.75, P = 0.017). PCNA immunostaining defines a good prognostic subgroup in adequately debulked patients with ovarian cancer.     

Information-seeking and maternal self-definition during the transition to motherhood.

The self-definitional processes accompanying the transition to motherhood were examined in this study. A cross-sectional sample of more than 600 women who were planning to get pregnant within 2 years, pregnant, or in the postpartum stage completed extensive questionnaires pertaining to their experiences of pregnancy and motherhood. On the basis of the assumption of the "self-socialization" perspective that individuals actively construct their identities in response to life transitions, our analyses focused on the role of information-seeking in the developing self-definitions of women becoming mothers. As predicted, (a) women actively sought information in anticipation of a first birth, (b) they used this information to construct identities incorporating motherhood, and (c) after the birth the determinants of their self-definitions shifted from indirect sources of information to direct experiences with child care. Hence, consistent with the self-socialization perspective, information-seeking did play an important role in the women's developing self-conceptions during this life transition. Mechanisms by which information gathered may alter self-conception are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Infants' intermodal knowledge about gender.

The aim of this study was to seek evidence of intermodal knowledge about gender in infants that would provide direct evidence of the existence of gender categories during the 1st yr of life. In Exp 1, 20 9- and 24 12-mo-olds were presented with pairs of male and female pictures with a female or male voice presented simultaneously. Ss spent significantly more time looking at the pictures matching the voices than at the same pictures paired with mismatching voices, but only in the case of female stimuli. Comparison to chance level performance suggested that the matching effect was more consistent in older Ss. In Exp 2, 20 9-mo-olds were tested with a set of highly stereotypical faces and distinctive male and female voices. Ss showed a preference for the faces matching the voices, but this effect was again restricted to female stimuli. Results of both studies suggest that intermodal knowledge about gender develops during the 2nd half of the 1st yr. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cell proliferation in the prostate complex of the castrate mouse

Cell proliferation during 100 h of continuous androgen challenge was studied in the seminal vesicle and coagulating gland of Balb/c mice castrated 3 days or 14 days prior to the first daily injection of 250 mug testosterone propionate. Continuous labelling with [3H] thymidine indicated that the seminal vesicle was almost totally responsive to androgen, as early as 3 days after castration, whereas the androgen sensitivity of the coagulating gland increased from 30% at 3 days after castration to 85% at 14 days after castration. In both tissues the magnitude of the proliferative reaction could be related to the extent of cell loss prior to stimulation. The duration of the pre-replicative phase in the response of the seminal vesicle to androgen was 20-25 h both at 3 and 14 days after castration. In the coagulating gland the pre-replicative phase was 40 h at 3 days after castration and 20 h at 14 days after castration. The maximum uptake of [7alpha-3H] testosterone administered to mice 3 days after castration was significantly greater (P less than 0-01) in the seminal vesicle compared to the coagulating gland. At 14 days the seminal vesicle and coagulating gland exhibited a similar capacity for uptake. The in vivo metabolism of [7alpha-3H] testosterone was studied by thin layer chromatography 30 min and 120 min after administration. A high proportion of the radioactivity extracted from all the tissues was associated with highly polar steroids. At 3 days after castration, the seminal vesicle, 2 h after administration of radioactive testosterone, retained a much higher proportion of radioactivity associated with dihydrotestosterone than did the coagulating gland. The localization of steroid in mice 3 days after castration was studied by dry-mount autoradiography at intervals up to 2 h after the injection of [1,2,6,7(n)-3H]-testosterone. A heavier deposition of silver grains was observed over autoradiographs of the seminal vesicle. In the seminal vesicle the grains were primarily located over nuclear areas whereas in the coagulating gland the grains were diffusely distributed over both nuclear areas and over cytoplasmic areas.     

AGATHA: Using heuristic search to automate the construction of case law theories

In this paper we describe AGATHA, a program designed to automate the process of theory construction in case based domains. Given a seed case and a number of precedent cases, the program uses a set of argument moves to generate a search space for a dialogue between the parties to the dispute. Each move is associated with a set of theory constructors, and thus each point in the space can be associated with a theory intended to explain the seed case and the other cases in the domain. The space is large and so an heuristic search method is needed. This paper describes two methods based on A* and alpha/beta pruning and also a series of experiments designed to explore the appropriateness of different evaluation functions, the most useful precedents to use as seed cases and the quality of the resulting theories.     

Divided attention during adaptation to visual-motor rotation in an endoscopic surgery simulator

We investigated how cognitive demand affects the acquisition of adaptive hand–eye coordination in a low-fidelity endoscopic simulator. Participants performed a peg transfer task. In the pre-exposure and post-exposure phases participants moved objects between pegs with forceps while directly viewing the pegboard. In the exposure phase participants completed that task while indirectly viewing the pegboard through a camera and monitor with a 90° clockwise visual rotation. A control group completed the experiment as described whereas an experimental group concurrently performed a short-term memory task (digit rehearsal) during the exposure phase. Performance was significantly disrupted during early exposure-phase performance for both groups. The cognitive task caused an additional initial performance decrement for the experimental group, but their performance quickly converged on control-group performance. Both groups performance improved over trials. Competition for attentional resources imposed by memory demands can impair simulator performance, but performers can quickly learn to compensate for the increased attentional demand.     

Dynamical Monte Carlo modelling of organic solar cells: the dependence of internal quantum efficiency on morphology

We present a dynamical Monte Carlo study of the dependence of the internal quantum efficiency (IQE) of an organic bulk heterojunction solar cell on the device morphology. The IQE is found to be strongly sensitive to the scale of phase separation in the morphology, with a peak at approximately 20 nm for the PFB/F8BT system studied. An ordered, checkered morphology exhibits a peak IQE 1.5 times higher than a disordered blend.     

Engineering thermal stability in RNA phage capsids via disulphide bonds

The RNA bacteriophages, a group that includes phages Qbeta and MS2, have a number of potential bionanotechnological applications, including cell specific drug delivery and as substrates for the formation of novel materials. Despite extensive sequence identity between their coat protein subunits, and an almost identical three-dimensional fold, Qbeta and MS2 capsids have dramatically different thermal stabilities. The increased stability of Qbeta has been correlated with the inter-subunit disulphide bonds present in that capsid and not present in MS2. We have tested this hypothesis directly using mass spectrometry. Analysis of the dissociated coat protein subunits suggests that inter-molecular disulphides are formed at the capsid five-fold but may not be at the three-fold axes. This conclusion has been tested by engineering disulphide cross-links into either the five-fold or three-fold positions of the recombinant MS2 capsid. Five-fold cross-linking results in a mutant with stability properties similar to those of Qbeta. Three-fold cross-linking results in a mutant unable to assemble T = 3 shells, implying that five-fold structures are on pathway to capsid assembly in these phages. The results demonstrate how it is possible to redesign the physical properties of phage shells and may be of general relevance to future applications of viruses and virus-like particles.