The microscopic origin of thermal cracking in rocks: An investigation by simultaneous time-of-flight neutron diffraction and acoustic emission monitoring

We demonstrate that neutron diffraction measurements make it possible to quantify elastic strains within the interior of solid samples, and thus have great potential for addressing a wide range of problems connected with the characterization of the mechanical properties of geological materials. We use the time-of-flight neutron diffraction technique, in combination with acoustic emission monitoring, to study the evolution of thermal strain within the interior of samples of a pure quartzite during slow heating, and the onset of the associated thermal cracking. Thermal cracking commences around 180 degreesC when the thermal strain deficit along the a-axes of quartz grains induces a thermal stress that is close to the bulk tensile strength of the rock

‘Free’ inhibin α subunit is expressed by bovine ovarian theca cells and its knockdown suppresses androgen production

Inhibins are ovarian dimeric glycoprotein hormones that suppress pituitary FSH production. They are synthesised by follicular granulosa cells as α plus βA/βB subunits (encoded by INHA, INHBA, INHBB, respectively). Inhibin concentrations are high in follicular fluid (FF) which is also abundant in ‘free’ α subunit, presumed to be of granulosal origin, but its role(s) remains obscure. Here, we report the unexpected finding that bovine theca cells show abundant INHA expression and ‘free’ inhibin α production. Thus, theca cells may contribute significantly to the inhibin α content of FF and peripheral blood. In vitro, knockdown of thecal INHA inhibited INSL3 and CYP17A1 expression and androgen production while INSL3 knockdown reduced INHA and inhibin α secretion. These findings suggest a positive role of thecal inhibin α on androgen production. However, exogenous inhibin α did not raise androgen production. We hypothesised that inhibin α may modulate the opposing effects of BMP and inhibin on androgen production. However, this was not supported experimentally. Furthermore, neither circulating nor intrafollicular androgen concentrations differed between control and inhibin α-immunized heifers, casting further doubt on thecal inhibin α subunit having a significant role in modulating androgen production. Role(s), if any, played by thecal inhibin α remain elusive

New evidence on Allyn Young's style and influence as a teacher

This paper publishes the hitherto unpublished correspondence between Allyn Abbott Young's biographer Charles Blitch and 17 of Young's former students or associates. Together with related biographical and archival material, the paper shows the way in which this adds to our knowledge of Young's considerable influence as a teacher upon some of the twentieth century's greatest economists. The correspondents are as follows: James W Angell, Colin Clark, Arthur H Cole, Lauchlin Currie, Melvin G de Chazeau, Eleanor Lansing Dulles, Howard S Ellis, Frank W Fetter, Earl J Hamilton, Seymour S Harris, Richard S Howey, Nicholas Kaldor, Melvin M Knight, Bertil Ohlin, Geoffrey Shepherd, Overton H Taylor, and Gilbert Walker

Pedigree analysis of Czech Holstein calves with schistosoma reflexum

<p>Abstract</p> <p>Background</p> <p>Schistosoma reflexum (SR) is congenital syndrome briefly characterized by visceral eventration, severe dorsoflexion and ankylosis of the spine and arthrogryposis. A genetic etiology has been proposed, but conclusive evidence has not yet been provided.</p> <p>Methods</p> <p>Pedigree analysis was carried out in 29 cases of SR in Czech Holsteins and Holstein crosses. Genetic relationship was evaluated and inbreeding coefficients calculated. Pedigrees of 15 Czech Holsteins fathering non-SR affected calves were used for comparison.</p> <p>Results</p> <p>Twenty-one cases occurred in one pedigree founded by three sires while three SR calves occurred in another pedigree with a common grandfather. The sex ratio between affected males and females was 11:6. Affected calves shared common ancestors different from those shared by the unaffected calves. The inbreeding coefficient in the SR affected calves was not increased compared to unaffected calves.</p> <p>Conclusions</p> <p>The findings are consistent with SR being inherited autosomal recessively. Further studies are however needed to confirm this and therefore a breeding trial is recommended where a suspected heterozygous sire is mated to closely related females.</p

The Mechanisms of Codon Reassignments in Mitochondrial Genetic Codes

Many cases of non-standard genetic codes are known in mitochondrial genomes. We carry out analysis of phylogeny and codon usage of organisms for which the complete mitochondrial genome is available, and we determine the most likely mechanism for codon reassignment in each case. Reassignment events can be classified according to the gain-loss framework. The gain represents the appearance of a new tRNA for the reassigned codon or the change of an existing tRNA such that it gains the ability to pair with the codon. The loss represents the deletion of a tRNA or the change in a tRNA so that it no longer translates the codon. One possible mechanism is Codon Disappearance, where the codon disappears from the genome prior to the gain and loss events. In the alternative mechanisms the codon does not disappear. In the Unassigned Codon mechanism, the loss occurs first, whereas in the Ambiguous Intermediate mechanism, the gain occurs first. Codon usage analysis gives clear evidence of cases where the codon disappeared at the point of the reassignment and also cases where it did not disappear. Codon disappearance is the probable explanation for stop to sense reassignments and a small number of reassignments of sense codons. However, the majority of sense to sense reassignments cannot be explained by codon disappearance. In the latter cases, by analysis of the presence or absence of tRNAs in the genome and of the changes in tRNA sequences, it is sometimes possible to distinguish between the Unassigned Codon and Ambiguous Intermediate mechanisms. We emphasize that not all reassignments follow the same scenario and that it is necessary to consider the details of each case carefully.Comment: 53 pages (45 pages, including 4 figures + 8 pages of supplementary information). To appear in J.Mol.Evo

Characterization of the molecular mechanisms of silicon uptake in coccolithophores

Coccolithophores are an important group of calcifying marine phytoplankton. Although coccolithophores are not silicified, some species exhibit a requirement for Si in the calcification process. These species also possess a novel protein (SITL) that resembles the SIT family of Si transporters found in diatoms. However, the nature of Si transport in coccolithophores is not yet known, making it difficult to determine the wider role of Si in coccolithophore biology. Here, we show that coccolithophore SITLs act as Na+-coupled Si transporters when expressed in heterologous systems and exhibit similar characteristics to diatom SITs. We find that CbSITL from Coccolithus braarudii is transcriptionally regulated by Si availability and is expressed in environmental coccolithophore populations. However, the Si requirement of C. braarudii and other coccolithophores is very low, with transport rates of exogenous Si below the level of detection in sensitive assays of Si transport. As coccoliths contain only low levels of Si, we propose that Si acts to support the calcification process, rather than forming a structural component of the coccolith itself. Si is therefore acting as a micronutrient in coccolithophores and natural populations are only likely to experience Si limitation in circumstances where dissolved silicon (DSi) is depleted to extreme levels

Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma

BACKGROUND: We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA) directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints. METHODS: From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse < 6 months after first course of chemotherapy). There was evidence of cisplatin resistance in 31 patients from their first ATP-TCA. Response to treatment was assessed by radiology, clinical assessment and tumor marker level (CA 125). RESULTS: The overall response rate was 59% (33/56) per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS) was 6.6 months per course of chemotherapy; median overall survival (OAS) for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9-12.8 months). CONCLUSION: The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centre

Association of a functional microsatellite within intron 1 of the BMP5 gene with susceptibility to osteoarthritis

<p>Abstract</p> <p>Background</p> <p>In a previous study carried out by our group, the genotyping of 36 microsatellite markers from within a narrow interval of chromosome 6p12.3-q13 generated evidence for linkage and for association to female hip osteoarthritis (OA), with the most compelling association found for a marker within intron 1 of the bone morphogenetic protein 5 gene (<it>BMP5</it>). In this study, we aimed to further categorize the association of variants within intron 1 of <it>BMP5 </it>with OA through an expanded genetic association study of the intron and subsequent functional analysis of associated polymorphisms.</p> <p>Methods</p> <p>We genotyped 18 common polymorphisms including 8 microsatellites and 9 single nucleotide polymorphisms (SNPs) and 1 insertion/deletion (INDEL) from within highly conserved regions between human and mouse within intron 1 of <it>BMP5</it>. These markers were then tested for association to OA by a two-stage approach in which the polymorphisms were initially genotyped in a case-control cohort comprising 361 individuals with associated polymorphisms (<it>P </it>≤ 0.05) then genotyped in a second case-control cohort comprising 1185 individuals.</p> <p>Results</p> <p>Two <it>BMP5 </it>intron 1 polymorphisms demonstrated association in the combined case-control cohort of 1546 individuals (765 cases and 781 controls): microsatellite D6S1276 (<it>P </it>= 0.018) and SNP rs921126 (<it>P </it>= 0.013). Functional analyses in osteoblastic, chondrocytic, and adipocytic cell lines indicated that allelic variants of D6S1276 have significant effects on the transcriptional activity of the <it>BMP5 </it>promoter <it>in vitro</it>.</p> <p>Conclusion</p> <p>Variability in gene expression of <it>BMP5 </it>may be an important contributor to OA genetic susceptibility.</p