How changes to how the Census counts people has implications for democracy and inequality

The US Census Bureau recently announced that it will be changing the demographics it measures and how it counts people. Hannah L. Walker and Rebecca U. Thorpe argue that the Bureau's revisions are an important opportunity to correct current practices of counting prisoners as residents where they are incarcerated rather than in their home communities. Such practices distort democratic representation and influence benefits and state aid

Investigating the role of Cten in metastatic colorectal cancer

Cten is upregulated in a number of tumour types and in colorectal cancer (CRC), expression is associated with advanced stage, poor prognosis and distant metastasis. Cten appears to regulate cell motility and it can confer features of stemness although, the knowledge of underlying signalling mechanisms is sparse. Cten is localised at focal adhesions and in the nucleus. It may promote cell motility through the regulation of cell adhesion and it may confer stemness through gene activation. To determine the biological activity of Cten in CRC, this thesis investigated three areas of Cten signalling. Nuclear expression of Cten is more prevalent in liver metastasis than the primary tumour. In the nucleus, Cten binds to β-catenin, however, the relevance of this is not known. To investigate the function of Cten in the nucleus, CRC cell lines were transfected with nuclear targeted Cten (NLSCten) and cell proliferation, migration and colony formation efficiency assessed. Expression profiling was performed to identify the underlying molecular mechanisms and additionally, the effect of Cten on β-catenin transcriptional activity was explored. Nuclear localised Cten was associated with increased cell migration and colony formation efficiency however it was found likely that Cten did not induce this activity through the regulation of β-catenin transcriptional activity. Activation of Epidermal growth factor receptor (EGFR) signalling in breast cell lines stimulates cell motility and upregulates Cten expression whilst simultaneously downregulating the expression of Tensin 3, known as the Tensin switch. Activity is mediated through signalling downstream to Deleted in liver cancer 1 (DLC1). This pathway was tested in CRC. Stimulation of CRC cell lines with recombinant Epidermal growth factor (EGF) and knockdown of Kirsten rat sarcoma viral oncogene homolog (Kras) resulted in up and downregulation of Cten respectively. A Tensin switch was not observed and, unexpectedly, Tensin 3 was stabilised by Cten signalling. Additionally, DLC1 was not expressed in the majority of cell lines investigated. It is possible that these mechanisms are either tissue dependent or different pathways operate in normal and cancer cell lines. Since Cten mediated cell migration was not regulated by a Tensin switch mechanism in CRC, other mechanisms of cell migration were sought. In CRC, Cten signalling downregulates E-cadherin expression. This prompted the investigation of Cten’s role in epithelial to mesenchymal transition (EMT) signalling. An EMT marker panel was investigated following the manipulation of Cten expression. Snail was identified as a novel target of Cten signalling and additionally, Cten was shown to promote the stabilisation of Snail protein. Furthermore, this signalling was functionally relevant and contributed to increased cell invasion and migration. To investigate Cten signalling, expression was manipulated using a dual approach of Cten forced expression using a plasmid expression construct and siRNA mediated knockdown. To develop more refined models, the novel, Clustered regularly interspaced short palindromic repeats – CRISPR associated nuclease 9 (CRISPR-Cas9) genome editing technology was utilised to create a Cten knockout SW620 cell line (SW620CtenKO) thus providing an alternative or supplementary method to interrogate Cten signalling in CRC. This study adds to the ongoing discussion of the role of Cten in cancer. It was confirmed that Cten was regulated by EGFR and Kras signalling but without a Tensin switch, however Cten did promote cell motility through the stabilisation of Snail suggesting that Cten may play a role in EMT processes. Finally, Cten displays enhanced oncogenic activity in the nucleus which may further promote metastasis. Further refinement of these pathways will increase the understanding of the invasion-metastasis cascade

Repurposing emoji for personalised communication::Why [pizza slice] means “I love you”

The use of emoji in digital communication can convey a wealth of emotions and concepts that otherwise would take many words to express. Emoji have become a popular form of communication, with researchers claiming emoji represent a type of “ubiquitous language” that can span different languages. In this paper however, we explore how emoji are also used in highly personalised and purposefully secretive ways. We show that emoji are repurposed for something other than their “intended” use between close partners, family members and friends. We present the range of reasons why certain emoji get chosen, including the concept of “emoji affordance” and explore why repurposing occurs. Normally used for speed, some emoji are instead used to convey intimate and personal sentiments that, for many reasons, their users cannot express in words. We discuss how this form of repurposing must be considered in tasks such as emoji-based sentiment analysis

Cten promotes Epithelial–Mesenchymal Transition (EMT) in colorectal cancer through stabilisation of Src

Cten is an oncogene promoting EMT in many signaling pathways, namely through Snail. We investigated whether Cten function could be mediated through Src. Cten levels were modulated by forced expression in HCT116 and gene knockdown in SW620 CRC (colorectal cancer) cell lines. In all cell lines, Cten was a positive regulator of Src expression. The functional importance of Src was tested by simultaneous Cten overexpression and Src knockdown. This resulted in abrogation of Cten motility-inducing activity and reduction of colony formation ability together with failure to induce Cten targets. In SW620ΔCten reduced Src expression increased following restoration of Cten, also leading to increased cell motility and colony formation, which were lost if Src was concomitantly knocked down. By qRT-PCR we showed modulation of Cten had no effect on Src mRNA. However, a CHX pulse chase assay demonstrated stabilization of Src protein by Cten. Finally, expression of Cten and Src was tested in a series of 84 primary CRCs and there was a significant correlation between them (P = 0.001). We conclude that Src is a novel and functionally important target of the Cten signaling pathway and that Cten protein causes post-transcriptional stabilization of Src in promoting EMT and possibly metastasis in CRC

Cten promotes epithelial-mesenchymal transition through post-transcriptional stabilization of Snail

Cten promotes cell migration however the knowledge of underlying signalling pathways is sparse. We have shown that Cten downregulates E-cadherin, a feature of epithelial to mesenchymal transition (EMT). This prompted us to investigate whether Cten further contributed to EMT processes to regulate cell motility.The regulation of Snail by Cten was investigated following overexpression, knockdown (by RNA-interference) or knockout of Cten in HCT116, Caco-2 and SW620 colorectal cancer (CRC) cell lines. Subsequently, the cycloheximide (CHX) pulse chase assay was used to investigate changes in Snail protein stability and the functional relevance of Cten-Snail signalling was investigated.Snail was identified as a downstream target of Cten signalling using multiple approaches of Cten expression manipulation. Furthermore, this activity was mediated through the SH2 domain of Cten. The CHX assay confirmed that Cten was regulating Snail at a post transcriptional level and this was through the prevention of Snail degradation. Cell migration, invasion and colony formation efficiency were increased following forced expression of GFP-Cten but subsequently lost when Snail was knocked down, demonstrating a functional Cten-Snail signalling axis.In conclusion, we have described a novel Cten-Snail signaling pathway that contributes to cell motility in CRC, mediated by the stabilization of Snail protein. This finding potentially furthers the understanding of EMT regulatory networks in cancer metastasis

Modulation of sirtuins during monolayer chondrocyte culture influences cartilage regeneration upon transfer to a 3D culture environment

This study examined the role of sirtuins in the regenerative potential of articular chondrocytes. Sirtuins (SIRT1-7) play a key role in regulating cartilage homeostasis. By inhibiting pro-inflammatory pathways responsible for cartilage degradation and promoting the expression of key matrix components, sirtuins have the potential to drive a favourable balance between anabolic and catabolic processes critical to regenerative medicine. When subjected to osmolarity and glucose concentrations representative of the in vivo niche, freshly isolated bovine chondrocytes exhibited increases in SIRT1 but not SIRT3 gene expression. Replicating methods adopted for the in vitro monolayer expansion of chondrocytes for cartilage regenerative therapies, we found that SIRT1 gene expression declined during expansion. Manipulation of sirtuin activity during in vitro expansion by supplementation with the SIRT1-specific activator SRT1720, nicotinamide mononucleotide, or the pan-sirtuin inhibitor nicotinamide, significantly influenced cartilage regeneration in subsequent 3D culture. Tissue mass, cellularity and extracellular matrix content were reduced in response to sirtuin inhibition during expansion, whilst sirtuin activation enhanced these measures of cartilage tissue regeneration. Modulation of sirtuin activity during monolayer expansion influenced H3K27me3, a heterochromatin mark with an important role in development and differentiation. Unexpectedly, treatment of primary chondrocytes with sirtuin activators in 3D culture reduced their matrix synthesis. Thus, modulating sirtuin activity during the in vitro monolayer expansion phase may represent a distinct opportunity to enhance the outcome of cartilage regenerative medicine techniques

Applicant Reactions to Artificial Intelligence in the Selection Process

The use of advanced technology such as artificial intelligence (AI) in the selection process has become an increasingly popular practice within organizations. However, little research has examined how applicants react to these new procedures and how those reactions may affect outcomes such as perceptions of fairness, organizational attraction, and job pursuit intentions. Previous research has suggested that the use of technology in the selection process may lead to more negative outcomes when compared to using traditional selection procedures such as face-to-face interviewing. The purpose of this study is to examine applicant reactions to the use of advanced decision-making technologies in the selection process, such as artificial intelligence systems that make hiring decisions. Determining how applicants react to the use of technology in the selection process serves to help organizations better understand how these practices affect job seekers’ perceptions of the organization. The results of this study may help organizations weigh the pros and cons of using computer information systems to select applicants instead of using a traditional selection procedure

Caesarean section and risk of unexplained stillbirth in subsequent pregnancy

Background Caesarean section is associated with an increased risk of disorders of placentation in subsequent pregnancies, but effects on the rate of antepartum stillbirth are unknown. We aimed to establish whether previous caesarean delivery is associated with an increased risk of antepartum stillbirth. Methods We linked pregnancy discharge data from the Scottish Morbidity Record (1980–98) and the Scottish Stillbirth and Infant Death Enquiry (1985–98). We estimated the relative risk of antepartum stillbirth in second pregnancies using time-to-event analyses. Findings For 120 633 singleton second births, there were 68 antepartum stillbirths in 17 754 women previously delivered by caesarean section (2–39 per 10 000 women per week) and 244 in 102879 women previously delivered vaginally (1·44; p<0·001). Risk of unexplained stillbirth associated with previous caesarean delivery differed significantly with gestational age (p=0·04); the excess risk was apparent from 34 weeks (hazard ratio 2·23 [95% Cl 1·48–3·36]). Risk was not attenuated by adjustment for maternal characteristics or outcome of the first pregnancy (2·74 [1·74–4·30]). The absolute risk of unexplained stillbirth at or after 39 weeks' gestation was 1·1 per 1000 women who had had a previous caesarean section and 0·5 per 1000 in those who had not. The difference was due mostly to an excess of unexplained stillbirths among women previously delivered by caesarean section. Interpretation Delivery by caesarean section in the first pregnancy could increase the risk of unexplained stillbirth in the second. In women with one previous caesarean delivery, the risk of unexplained antepartum stillbirth at or after 39 weeks' gestation is about double the risk of stillbirth or neonatal death from intrapartum uterine rupture