Review of industry-proposed in-pile thermionic space reactors. Volume I - General

Diode and reactor design and nuclear fuels including uranium carbide alloys, uranium dioxide and uranium dioxide cermets for industry proposed in-pile thermionic space reactor

The abundance of health-associated bacteria is altered in PAH polluted soils-Implications for health in urban areas?

Long-term exposure to polyaromatic hydrocarbons (PAHs) has been connected to chronic human health disorders. It is also well-known that i) PAH contamination alters soil bacterial communities, ii) human microbiome is associated with environmental microbiome, and iii) alteration in the abundance of members in several bacterial phyla is associated with adverse or beneficial human health effects. We hypothesized that soil pollution by PAHs altered soil bacterial communities that had known associations with human health. The rationale behind our study was to increase understanding and potentially facilitate reconsidering factors that lead to health disorders in areas characterized by PAH contamination. Large containers filled with either spruce forest soil, pine forest soil, peat, or glacial sand were left to incubate or contaminated with creosote. Biological degradation of PAHs was monitored using GC-MS, and the bacterial community composition was analyzed using 454 pyrosequencing. Proteobacteria had higher and Actinobacteria and Bacteroidetes had lower relative abundance in creosote contaminated soils than in non-contaminated soils. Earlier studies have demonstrated that an increase in the abundance of Proteobacteria and decreased abundance of the phyla Actinobacteria and Bacteroidetes are particularly associated with adverse health outcomes and immunological disorders. Therefore, we propose that pollution-induced shifts in natural soil bacterial community, like in PAH-polluted areas, can contribute to the prevalence of chronic diseases. We encourage studies that simultaneously address the classic "adverse toxin effect" paradigm and our novel "altered environmental microbiome" hypothesis.Peer reviewe

Emotions in business-to-business service relationships

Emotion in business-to-business service relationships regarding cargo services is explored. The service relationship is characterised by mutual trust and cooperation. Contact is mainly via telephone or e-mail with some face-to-face interactions and participants providing a complex, multi-skilled seamless service. Experience rather than training plays a vital role with long-term service relationships built up and maintained. Emotional sensitivity is acquired partly by experience and a repeat customer base but mainly through a genuine desire to help and get to know others. In contrast to the view of emotional labour bringing managerial control or adverse affects to service staff, the emotion engendered by this work is authentic expression bringing personal satisfaction

Effects of Different Exercise Training Protocols on Gene Expression of Rac1 and PAK1 in Healthy Rat Fast- and Slow-Type Muscles

Purpose Rac1 and its downstream target PAK1 are novel regulators of insulin and exercise-induced glucose uptake in skeletal muscle. However, it is not yet understood how different training intensities affect the expression of these proteins. Therefore, we studied the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on Rac1 and PAK1 expression in fast-type (gastrocnemius, GC) and slow-type (soleus, SOL) muscles in rats after HIIT and MICT swimming exercises. Methods The mRNA expression was determined using qPCR and protein expression levels with reverse-phase protein microarray (RPPA). Results HIIT significantly decreased Rac1 mRNA expression in GC compared to MICT (p = 0.003) and to the control group (CON) (p = 0.001). At the protein level Rac1 was increased in GC in both training groups, but only the difference between HIIT and CON was significant (p = 0.02). HIIT caused significant decrease of PAK1 mRNA expression in GC compared to MICT (p = 0.007) and to CON (p = 0.001). At the protein level, HIIT increased PAK1 expression in GC compared to MICT and CON (by similar to 17%), but the difference was not statistically significant (p = 0.3, p = 0.2, respectively). There were no significant differences in the Rac1 or PAK1 expression in SOL between the groups. Conclusion Our results indicate that HIIT, but not MICT, decreases Rac1 and PAK1 mRNA expression and increases the protein expression of especially Rac1 but only in fast-type muscle. These exercise training findings may reveal new therapeutic targets to treat patients with metabolic diseases

CIP2A Interacts with TopBP1 and Drives Basal-Like Breast Cancer Tumorigenesis

Basal-like breast cancers (BLBC) are characterized by defects in homologous recombination (HR), deficient mitotic checkpoint, and high-proliferation activity. Here, we discover CIP2A as a candidate driver of BLBC. CIP2A was essential for DNA damage-induced initiation of mouse BLBC-like mammary tumors and for survival of HR-defective BLBC cells. CIP2A was dispensable for normal mammary gland development and for unperturbed mitosis, but selectively essential for mitotic progression of DNA damaged cells. A direct interaction between CIP2A and a DNA repair scaffold protein TopBP1 was identified, and CIP2A inhibition resulted in enhanced DNA damage-induced TopBP1 and RAD51 recruitment to chromatin in mammary epithelial cells. In addition to its role in tumor initiation, and survival of BRCA-deficient cells, CIP2A also drove proliferative MYC and E2F1 signaling in basal-like triple-negative breast cancer (BL-TNBC) cells. Clinically, high CIP2A expression was associated with poor patient prognosis in BL-TNBCs but not in other breast cancer subtypes. Small-molecule reactivators of PP2A (SMAP) inhibited CIP2A transcription, phenocopied the CIP2A-deficient DNA damage response (DDR), and inhibited growth of patient-derived BLBC xenograft. In summary, these results demonstrate that CIP2A directly interacts with TopBP1 and coordinates DNAdamage-induced mitotic checkpoint and proliferation, thereby driving BLBC initiation and progression. SMAPs could serve as a surrogate therapeutic strategy to inhibit the oncogenic activity of CIP2A in BLBCs. Significance: These results identify CIP2A as a nongenetic driver and therapeutic target in basal-like breast cancer that regulates DNA damage-induced G2-M checkpoint and proliferative signaling.Peer reviewe

Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution

APOBEC3 enzymes are cytosine deaminases implicated in cancer. Precisely when APOBEC3 expression is induced during cancer development remains to be defined. Here we show that specific APOBEC3 genes are upregulated in breast DCIS, and in pre-invasive lung cancer lesions coincident with cellular proliferation. We observe evidence of APOBEC3-mediated subclonal mutagenesis propagated from TRACERx pre-invasive to invasive NSCLC lesions. We find that APOBEC3B exacerbates DNA replication stress and chromosomal instability through incomplete replication of genomic DNA, manifested by accumulation of mitotic ultrafine bridges and 53BP1 nuclear bodies in the G1 phase of the cell cycle. Analysis of TRACERx NSCLC clinical samples and mouse lung cancer models, revealed APOBEC3B expression driving replication stress and chromosome missegregation. We propose that APOBEC3 is functionally implicated in the onset of chromosomal instability and somatic mutational heterogeneity in pre-invasive disease, providing fuel for selection early in cancer evolution

Apolipoprotein E Genotype and Cardiovascular Diseases in the Elderly

The apolipoprotein E (APOE) genotype is a genetic risk factor for dementia, Alzheimer’s disease, and cardiovascular disease (CVD). It includes three alleles (e2, e3, e4) that are located on chromosome 19q3.2. The e3 allele is the most common and is more common in people of Northern European ancestry and less common in those of Asian ancestry. Those with at least one e4 allele are at increased risk for CVD outcomes. It is well established that the presence of an e4 allele is linked to higher low-density lipoprotein cholesterol levels, even at young ages. Even though most CVD occurs in older people, there are few studies of the effects of APOE on CVD in older people. This review addresses recent research on the links between APOE, CVD, and vascular mechanisms by which APOE may affect CVD in the elderly

Examining the impact of digital technologies on students’ Higher Education outcomes:The case of the Virtual Learning Environment and social media

Digital natives is a term used to describe current higher education (HE) students, whose lives are proliferated by digital technologies. To cater to the needs of this new generation of students, HE institutions increasingly adopt digital tools such as virtual learning environments (VLE) and social media (SM). Little is known, however, about the impact of these digital technologies on students’ HE outcomes. Drawing from service productivity theories, this study aims to address this gap. Through exploratory sequential mixed research methods, we identify five HE outcomes and reveal that Learning-Oriented Outcomes are the most important in HE even when digital technologies are not used; and these outcomes are further enhanced when students use VLE. Learning-Oriented Outcomes, however, are the least important when SM is used in HE; students tend to prioritise outcomes related to Knowledge Transfer instead. Our research findings derive theoretical and practical contributions and open up avenues for future research

Key role for ubiquitin protein modification in TGFβ signal transduction

The transforming growth factor β (TGFβ) superfamily of signal transduction molecules plays crucial roles in the regulation of cell behavior. TGFβ regulates gene transcription through Smad proteins and signals via non-Smad pathways. The TGFβ pathway is strictly regulated, and perturbations lead to tumorigenesis. Several pathway components are known to be targeted for proteasomal degradation via ubiquitination by E3 ligases. Smurfs are well known negative regulators of TGFβ, which function as E3 ligases recruited by adaptors such as I-Smads. TGFβ signaling can also be enhanced by E3 ligases, such as Arkadia, that target repressors for degradation. It is becoming clear that E3 ligases often target multiple pathways, thereby acting as mediators of signaling cross-talk. Regulation via ubiquitination involves a complex network of E3 ligases, adaptor proteins, and deubiquitinating enzymes (DUBs), the last-mentioned acting by removing ubiquitin from its targets. Interestingly, also non-degradative ubiquitin modifications are known to play important roles in TGFβ signaling. Ubiquitin modifications thus play a key role in TGFβ signal transduction, and in this review we provide an overview of known players, focusing on recent advances