Erythroid Kruppel-like factor directly activates the basic Kruppel-like factor gene in erythroid cells

The Sp/Kriippel-like factor (Sp/KIf) family is comprised of around 25 zinc finger transcription factors that recognize CACCC boxes and GC-rich elements. We have investigated basic Kruppel-like factor (Bklf/Klf3) and show that in erythroid tissues its expression is highly dependent on another family member, erythroid Kruppel-like factor (Eklf/Kif1). We observe that Bklf mRNA is significantly reduced in erythroid tissues from Eklf-null murine embryos. We find that Bklf is driven primarily by two promoters, a ubiquitously active GC-rich upstream promoter, la, and an erythroid downstream promoter, 1b. Transcripts from the two promoters encode identical proteins. Interestingly, both the ubiquitous and the erythroid promoter are dependent on Eklf in erythroid cells. Eklf also activates both promoters in transient assays. Experiments utilizing an inducible form of Eklf demonstrate activation of the endogenous Bklf gene in the presence of an inhibitor of protein synthesis. The kinetics of activation are also consistent with Bklf being a direct Eklf target. Chromatin immunoprecipitation assays confirm that Eklf associates with both Bklf promoters. Eklf is typically an activator of transcription, whereas Bklf is noted as a repressor. Our results support the hypothesis that feedback cross-regulation occurs within the Sp/Klf family in vivo

Genome sequence of Burkholderia pseudomallei NCTC 13392

Here, we describe the draft genome sequence of Burkholderia pseudomallei NCTC 13392. This isolate has been distributed as K96243, but distinct genomic differences have been identified. The genomic sequence of this isolate will provide the genomic context for previously conducted functional studies

Three-dimensional reconstruction of cell nuclei, internalized quantum dots and sites of lipid peroxidation

BACKGROUND: The purpose of the study was to develop and illustrate three-dimensional (3-D) reconstruction of nuclei and intracellular lipid peroxidation in cells exposed to oxidative stress induced by quantum dots. Programmed cell death is characterized by multiple biochemical and morphological changes in different organelles, including nuclei, mitochondria and lysosomes. It is the dynamics of the spatio-temporal changes in the signalling and morphological adaptations which will ultimately determine the 'shape' and fate of the cell. RESULTS: We present new approaches to the 3-D reconstruction of organelle morphology and biochemical changes in confocal live-cell images. We demonstrate the 3-D shapes of nuclei, the 3-D intracellular distributions of QDs and the accompanying lipid-membrane peroxidation, and provide methods for quantification. CONCLUSION: This study provides an approach to 3-D organelle and nanoparticle visualization in the context of cell death; however, this approach is also applicable more generally to investigating changes in organelle morphology in response to therapeutic interventions, stressful stimuli and internalized nanoparticles. Moreover, the approach provides quantitative data for such changes, which will help us to better integrate compartmentalization of subcellular events and to link morphological and biochemical changes with physiological outcomes

The degraded concept representation system in semantic dementia:damage to pan-modal hub, then visual spoke

The core clinical feature of semantic dementia is a progressive yet selective degradation of conceptual knowledge. Understanding the cognitive and neuroanatomical basis for this deficit is a key challenge for both clinical and basic science. Some researchers attribute the deficit to damage to pan-modal conceptual representations that are independent of any particular sensory-motor modality and are represented in the ventrolateral anterior temporal lobes. Others claim that damage to modality-specific visual feature representations in the occipitotemporal 'ventral stream' is responsible. In the present study, we tested the hypothesis that concept degradation in semantic dementia involves a combination of these pan-modal and modality-specific elements. We investigated factors influencing knowledge of object concepts by analysing 43 sets of picture-naming data from patients with semantic dementia. We found a strong influence of two pan-modal factors: highly familiar and typical items were named more accurately than less familiar/atypical items at all stages of the disorder. Items associated with rich sensory-motor information were also named more successfully at all stages, and this effect was present for sound/motion knowledge and tactile/action knowledge when these modalities were studied separately. However, there was no advantage for items rich in visual colour/form characteristics; instead, this factor had an increasingly negative impact in the later stages of the disorder. We propose that these results are best explained by a combination of (i) degradation of modality-independent conceptual representations, which is present throughout the disorder and is a consequence of atrophy focused on the ventrolateral anterior temporal lobes; and (ii) a later additional deficit for concepts that depend heavily on visual colour/form information, caused by the spreading of atrophy to posterior ventral temporal regions specialized for representing this information. This explanation is consistent with a graded hub-and-spoke model of conceptual knowledge, in which there is a gradual convergence of information along the temporal lobes, with visual attributes represented in the posterior cortex giving way to pan-modal representations in the anterior areas. © 2012 The Author

On the calculation of surface areas of objects reconstructed from serial sections

Abstract This paper concerns certain aspects of the calculation of the surface area of objects reconstructed from serial sections. The main points discussed are (1) the relative importance of the number of sections compared to the number of segments taken around the contour in each section; and (2) the fact that the error in the estimated surface area may actually become worse as the number of sections increases. The number of sections should be made large enough to reproduce the three-dimensional shape of the object, but not too much larger; the number of segments around the contours should then be made large enough that the segment size is similar to or smaller than the section thickness

Use of bioengineered human commensal gut bacteria-derived microvesicles for mucosal plague vaccine delivery and immunization

Plague caused by the Gram-negative bacterium, Yersinia pestis, is still endemic in parts of the world today. Protection against pneumonic plague is essential to prevent the development and spread of epidemics. Despite this, there are currently no licensed plague vaccines in the western world. Here we describe the means of delivering biologically active plague vaccine antigens directly to mucosal sites of plague infection using highly stable microvesicles (outer membrane vesicles; OMVs) that are naturally produced by the abundant and harmless human commensal gut bacterium Bacteroides thetaiotaomicron (Bt). Bt was engineered to express major plague protective antigens in its OMVs, specifically Fraction 1 (F1) in the outer membrane and LcrV (V antigen) in the lumen, for targeted delivery to the gastrointestinal (GI) and respiratory tracts in a non-human primate (NHP) host. Our key findings were that Bt OMVs stably expresses F1 and V plague antigens, particularly the V antigen, in the correct, immunogenic form. When delivered intranasally V-OMVs elicited substantive and specific immune and antibody responses, both in the serum [immunoglobulin (Ig)G] and in the upper and lower respiratory tract (IgA); this included the generation of serum antibodies able to kill plague bacteria. Our results also showed that Bt OMV-based vaccines had many desirable characteristics, including: biosafety and an absence of any adverse effects, pathology or gross alteration of resident microbial communities (microbiotas); high stability and thermo-tolerance; needle-free delivery; intrinsic adjuvanticity; the ability to stimulate both humoral and cell-mediated immune responses; and targeting of primary sites of plague infection

Intergenerational equity in municipal accounting: New Zealand 1910s

Accounting for fixed assets by municipalities has been discussed in the accounting history literature previously. This paper addresses two issues related to accounting for fixed assets not previously discussed; the influence of the principle of intergenerational equity on local government accounting, and the influence of users of accounting information in accounting policy making in government accounting. The paper identifies that users of accounting information have had significant influence in a debate on government accounting policy, and that the principle of intergenerational equity was given a position of high importance in the debate, but not an unchallengeable position. The motivation of the users of accounting information to engage in the debates is identified as a form of civic duty, which is consistent with the ethical imperative in ensuring intergenerational equity

Guidance on clinical research involving infants, children and young people: an update for researchers and research ethics committees

The British Paediatric Association, the forerunner of the Royal College of Paediatrics and Child Health (RCPCH), first published guidance in relation to research involving children in 1980.1 Prior to this time, little clinical research involved children. The 1980 guidance initiated a sea change, stating ‘research involving children is important’, ‘should be supported and encouraged’ and ‘research which involves a child and is of no benefit to that child (non-therapeutic research) is not necessarily either unethical or illegal’. Updated guidance was issued by the RCPCH in 2000.2 Both documents have been cited extensively

Internal accounting practices at Whitbread & Company c.1890-1925

This paper examines internal accounting practices at Whitbread & Company from c. 1890 to 1925. At this time, there was an increasing interest in cost accounting, but there is little detailed extant research on general internal accounting practices of firms. The brewing sector, we suggest, is a potentially fruitful realm to further our knowledge of this time. Drawing on the Whitbread brewery archival records, we chart the internal accounting practices of the company. Our findings reveal a stable set of accounting practices, focused mainly on bookkeeping, although the firm’s auditor produced some reports which may have been useful for management decision-making. We argue these practices were highly institutionalised, and seemingly resistant to external forces present in the company’s environment