Modelling the formation of necrotic regions in avascular tumours

The mechanisms underlying the formation of necrotic regions within avascular tumours are not well understood. In this paper, we examine the relative roles of nutrient deprivation and of cell death, from both the proliferating phase of the cell cycle via apoptosis and from the quiescent phase via necrosis, in changing the structure within multicellular tumour spheroids and particularly the accumulation of dead cell material in the centre. A mathematical model is presented and studied that accounts for nutrient diffusion, changes in cell cycling rates, the two different routes to cell death as well as active motion of cells and passive motion of the dead cell material. In studying the accumulation of dead cell matter we do not distinguish between the route by which each was formed. The resulting mathematical model is examined for a number of scenarios. Results show that in many cases the size of the necrotic core is closely correlated with low levels in nutrient concentration. However, in certain cases, particularly where the rate of necrosis is large, the resulting necrotic core can lead to regions of non-negligible nutrient concentration-dependent upon the mode of cell death.

Age relationships beteen low level rock platforms and the high coastal slopes in Jersey and the surrounding area.

Recent research along the coastal cliffs and embayments of Jersey has revealed new aspects of the geomorphology of the rocky shore platform and its relationship with the steep slopes that link it to the island plateau above. Specifically, a rockhead platform meets a 10-30 m high, near vertical cliff at approximately 8-10 m above Jersey Datum (J.D.= ±0 m Ordnance Datum; likewise Guernsey Datum: G.D.), slopes down-towards mid-tide levels becoming ever more deeply dissected. Generalised contours of this platform show it to be distinct from a lower tidal rockhead platform which is comparatively smooth over large areas as it undergoes continuing contemporary abrasion. This lower platform is generally separated from the higher one by low cliffs, less than a metre high at mid-tidal levels, but two to three metres at the base of the backing cliffs. Both of these platforms are shown to antedate the Last Cold Stage (Devensian) head at a number of localities and this relationship is taken to represent the general situation, not only in Jersey, but throughout the other Channel Islands and adjacent coasts of Armorica. Whether either, or both, of these two platforms are older than Marine Oxygen Isotope Substage (MOIS) 5e (Ipswichian) as well is not known. However the considerable age of the numerous and wide intertidal shore platforms of the Channel Islands and adjacent coasts of Amorica makes a greater age quite possible.

Variation in 16S-23S rRNA intergenic spacer regions in Photobacterium damselae: a mosaic-like structure

Phenotypically, Photobacterium damselae subsp. piscicida and P. damselae subsp. damselae are easily distinguished. However, their 16S rRNA gene sequences are identical, and attempts to discriminate these two subspecies by molecular tools are hampered by their high level of DNA-DNA similarity. The 16S-23S rRNA internal transcribed spacers (ITS) were sequenced in two strains of Photobacterium damselae subsp. piscicida and two strains of P. damselae subsp. damselae to determine the level of molecular diversity in this DNA region. A total of 17 different ITS variants, ranging from 803 to 296 bp were found, some of which were subspecies or strain specific. The largest ITS contained four tRNA genes (tDNAs) coding for tRNA(Glu(UUC)), tRNA(LyS(UUU)), tRNA(Val(UAC)), and tRNA(Ala(GGC)). Five amplicons contained tRNA(Glu(UUC)) combined with two additional tRNA genes, including tRNA(Lys(UUU)), tRNA(Val(UAC)), or tRNA(Ala(UGC)). Five amplicons contained tRNA(Ile(GAU)) and tRNA(Ala(UGC)). Two amplicons contained tRNA(Glu(UUC)) and tRNA(Val(UGC)). Two different isoacceptor tRNA(Ala) genes (GGC and UGC anticodons) were found. The five smallest amplicons contained no tRNA genes. The tRNA-gene combinations tRNA(Glu(UUC)) -tRNA(Val(UAC)) -tRNA(Ala(UGC)) and tRNA(Glu(UUC)) -tRNA(Ala(UGC)) have not been previously reported in bacterial ITS regions. The number of copies of the ribosomal operon (rrn) in the P. damselae chromosome ranged from at least 9 to 12. For ITS variants coexisting in two strains of different subspecies or in strains of the same subspecies, nucleotide substitution percentages ranged from 0 to 2%. The main source of variation between ITS variants was due to different combinations of DNA sequence blocks, constituting a mosaic-like structure.

Motor brain regions are involved in the encoding of delayed intentions: a fMRI study

In studies of prospective memory, recall of the content of delayed intentions is normally excellent, probably because they contain actions that have to be enacted at a later time. Action words encoded for later enactment are more accessible from memory than those encoded for later verbal report [Freeman, J.E., and Ellis, J.A. 2003a. The representation of delayed intentions: A prospective subject-performed task? Journal of Experimental Psychology: Learning, Memory, and Cognition, 29, 976-992.]. As this higher assessibility is lost when the intended actions have to be enacted during encoding, or when a motor interference task is introduced concurrent to intention encoding, Freeman and Ellis suggested that the advantage of to-be-enacted actions is due to additional preparatory motor operations during encoding. Accordingly, in a fMRI study with 10 healthy young participants, we investigated whether motor brain regions are differentially activated during verbal encoding of actions for later enactment with the right hand in contrast to verbal encoding of actions for later verbal report. We included an additional condition of verbal encoding of abstract verbs for later verbal report to investigate whether the semantic motor information inherent in action verbs in contrast to abstract verbs activates motor brain regions different from those involved in the verbal encoding of actions for later enactment. Differential activation for the verbal encoding of to-be-enacted actions in contrast to to-be-reported actions was found in brain regions known to be involved in covert motor preparation for hand movements, i.e. the postcentral gyrus, the precuneus, the dorsal and ventral premotor cortex, the posterior middle temporal gyrus and the inferior parietal lobule. There was no overlap between these brain regions and those differentially activated during the verbal encoding of actions in contrast to abstract verbs for later verbal report. Consequently, the results of this fMRI study suggest the presence of preparatory motor operations during the encoding of delayed intentions requiring a future motor response, which cannot be attributed to semantic information inherent to action verbs. (c) 2006 Elsevier B.V. All rights reserved.

‘Once a miner, always a miner’: Poverty and livelihood diversification in Akwatia, Ghana

This paper offers an alternative viewpoint on why people choose to engage in artisanal mining – the low tech mineral extraction and processing of mainly precious metals and stones – for extended periods in sub-Saharan Africa. Drawing upon experiences from Akwatia, Ghana’s epicentre of diamond production since the mid-1920s, the analysis challenges the commonly-held view that the region’s people are drawn to artisanal mining solely because of a desire ‘to get rich quick’. A combination of events, including the recent closure of Ghana Consolidated Diamonds Ltd’s industrial-scale operation and decreased foreign investment in the country’s diamond industry over concerns of it potentially harbouring ‘conflict’ stones from neighbouring Coˆte D’Ivoire, has had a debilitating economic impact on Akwatia. In an attempt to alleviate their hardships, many of the town’s so-called ‘lifetime’ diamond miners have managed to secure employment in neighbouring artisanal gold mining camps. But their decision has been condemned by many of the country’s policymakers and traditional leaders, who see it solely as a move to secure ‘fast money’. It is argued here, however, that these people pursue work in surrounding artisanal gold mining communities mainly because of poverty, and that their decision has more to do with a desire to immerse in activities with which they are familiar, that offer stable employment and consistent salaries, and provide immediate debt relief. Misdiagnosis of cases such as Akwatia underscores how unfamiliar policymakers and donors are with the dynamics of ASM in sub-Saharan Africa.

Gene expression profiling of human hibernating myocardium: Increased expression of B-type natriuretic peptide and proenkephalin in hypocontractile vs normally-contracting regions of the heart

A greater understanding of the molecular basis of hibernating myocardium may assist in identifying those patients who would most benefit from revascularization. Paired heart biopsies were taken from hypocontractile and normally-contracting myocardium (identified by cardiovascular magnetic resonance) from 6 patients with chronic stable angina scheduled for bypass grafting. Gene expression profiles of hypocontractile and normally-contracting samples were compared using Affymetrix microarrays. The data for patients with confirmed hibernating myocardium were analysed separately and a different, though overlapping, set (up to 380) of genes was identified which may constitute a molecular fingerprint for hibernating myocardium. The expression of B-type natriuretic peptide (BNP) was increased in hypocontractile relative to normally-contracting myocardium. The expression of BNP correlated most closely with the expression of proenkephalin and follistatin 3, which may constitute additional heart failure markers. Our data illustrate differential gene expression in hypocontractile and/hibernating myocardium relative to normally-contracting myocardium within individual human hearts. Changes in expression of these genes, including increased relative expression of natriuretic and other factors, may constitute a molecular signature for hypocontractile and/or hibernating myocardium.

Distributed water ingress and water potential measurements using fibre optics

We report on a distributed moisture detection scheme which uses a cable design based on waterswellable hydrogel polymers. The cable modulates the loss characteristic of light guided within a multi-mode optical fibre in response to relative water potentials in the surrounding environment. Interrogation of the cable using conventional optical time-domain reflectometry (OTDR) instruments allows water ingress points to be identified and located with a spatial resolution of 50 cm. The system has been tested in a simulated tendon duct grouting experiment as a means of mapping the extent of fill along the duct during the grouting process. Voided regions were detected and identified to within 50 cm. A series of salt solutions has been used to determine the sensor behaviour over a range of water potentials. These experiments predict that measurements of soil moisture content can be made over the range 0 to – 1500 kPa. Preliminary data on soil measurements have shown that the sensor can detect water pressure changes with a resolution of 45 kPa. Applications for the sensor include quality assurance of grouting procedures, verification of waterproofing barriers and soil moisture content determination (for load-bearing calculations).

The changing atmospheric water cycle in polar regions in a warmer climate

We have examined the atmospheric water cycle of both Polar Regions, pole wards of 60°N and 60°S, using the ERA-Interim re-analysis and high-resolution simulations with the ECHAM5 model for both the present and future climate based on the IPCC, A1B scenario, representative of the last three decades of the 21st century. The annual precipitation in ERA-Interim amounts to ~17000 km3 and is more or less the same in the Arctic and the Antarctic, but it is composed differently. In the Arctic the annual evaporation is some 8000 km3 but some 3000 km3 less in the Antarctica where the net horizontal transport is correspondingly larger. The net water transport of the model is more intense than in ERA-Interim, in the Arctic the difference is 2.5% and in the Antarctic it is 6.2%. Precipitation and net horizontal transport in the Arctic has a maximum in August and September. Evaporation peaks in June and July. The seasonal cycle is similar in Antarctica with the highest precipitation in the austral autumn. The largest net transport occurs at the end of the major extra-tropical storm tracks in the Northern Hemisphere such as the eastern Pacific and eastern north Atlantic. The variability of the model is virtually identical to that of the re-analysis and there are no changes in variability between the present climate and the climate at the end of the 21st century when normalized with the higher level of moisture. The changes from year to year are substantial with the 20 and 30-year records being generally too short to identify robust trends in the hydrological cycle. In the A1B climate scenario the strength of the water cycle increases by some 25% in the Arctic and by 19% in the Antarctica, as measured by annual precipitation. The increase in the net horizontal transport is 29% and 22% respectively, and the increase in evaporation correspondingly less. The net transport follows closely the Clausius-Clapeyron relation. There is 2 a minor change in the annual cycle of the Arctic atmospheric water cycle with the maximum transport and precipitation occurring later in the year. There is a small imbalance of some 4-6% between the net transport and precipitation minus evaporation. We suggest that this is mainly due to the fact the transport is calculated from instantaneous 6-hourly data while precipitation and evaporation is accumulated over a 6 hour period. The residual difference is proportionally similar for all experiments and hardly varies from year to year.

Patterns of nucleotide substitution in angiosperm cpDNA trnL (UAA)-trnF (GAA) regions

Patterns of substitution in chloroplast encoded trnL_F regions were compared between species of Actaea (Ranunculales), Digitalis (Scrophulariales), Drosera (Caryophyllales), Panicoideae (Poales), the small chromosome species clade of Pelargonium (Geraniales), each representing a different order of flowering plants, and Huperzia (Lycopodiales). In total, the study included 265 taxa, each with > 900-bp sequences, totaling 0.24 Mb. Both pairwise and phylogeny-based comparisons were used to assess nucleotide substitution patterns. In all six groups, we found that transition/transversion ratios, as estimated by maximum likelihood on most-parsimonious trees, ranged between 0.8 and 1.0 for ingroups. These values occurred both at low sequence divergences, where substitutional saturation, i.e., multiple substitutions having occurred at the same (homologous) nucleotide position, was not expected, and at higher levels of divergence. This suggests that the angiosperm trnL-F regions evolve in a pattern different from that generally observed for nuclear and animal mtDNA (transitional/transversion ratio > or = 2). Transition/transversion ratios in the intron and the spacer region differed in all alignments compared, yet base compositions between the regions were highly similar in all six groups. A>-C transversions were significantly less frequent than the other four substitution types. This correlates with results from studies on fidelity mechanisms in DNA replication that predict A<->T and G<->C transversions to be least likely to occur. It therefore strengthens confidence in the link between mutation bias at the polymerase level and the actual fixation of substitutions as recorded on evolutionary trees, and concomitantly, in the neutrality of nucleotide substitutions as phylogenetic markers.