Irresponsible contagions: Propagating harmful behavior through imitation

‘Monkey see, monkey do’ is an old saying referring to imitating another\u27s actions without necessarily understanding the underlying motivations or being concerned about consequences, such as propagating harmful behaviors. This study examines the likelihood of firms imitating and proliferating others’ unethical, irresponsible practices thereby exacerbating harmful effects among even more firms; in doing so, irresponsible contagions can rapidly spread more broadly, negatively affecting even more consumers. Building upon rivalry- and information-based imitation theories, we examine if harmful behaviors of others, in combination with misbehavior of referent firms, influences the likelihood of a firm to engage in irresponsible consumer-related practices. After examining 25,824 firm-year observations over 12 years, our findings suggest that imitation of harmful product-related behavior occurs; with size an important factor related to proliferation of harmful behaviors. Testing the model against a holdout sample finds 94% accuracy. Implications for scholars, managers, and policy makers are explored

Preorganized tridentate analogues of mixed hydroxyoxime/carboxylate nickel extractants

Simple tridentate ligands can operate as Ni-extractants in the pH-dependent process: 2LHorg + NiSO4 ⇌ [(L)2Ni]org + H2SO4.</p

Glioma-derived exosomes drive the differentiation of neural stem cells to astrocytes

Exosomes appear to be effective inter-cellular communicators delivering several types of molecules, such as proteins and RNAs, suggesting that they could influence neural stem cell (NSC) differentiation. Our RNA sequencing studies demonstrated that the RNAs related to cell proliferation and astrocyte differentiation were upregulated in human mesenchymal stem cells (hMSC) when co-cultured with exosomes obtained from the culture medium of human glioma cells (U87). Metallothionein 3 and elastin genes, which are related to cell proliferation, increased 10 and 7.2 fold, respectively. Expression of genes for astrocyte differentiation, such as tumor growth factor alpha, induced protein 3 of the NOTCH1 family, colony stimulating factor and interleukin 6 of the STAT3 family and Hes family bHLH transcription factor 1 also increased by 2.3, 10, 4.7 and 2.9 fold, respectively. We further examined the effects of these exosomes on rat fetal neural stem cell (rNSC) differentiation using the secreted exosomes from U87 glioma cells or exosomes from U87 cells that were stimulated with interleukin 1β (IL-1β). The rNSCs, extracted from rat brains at embryonic day 14 (E14), underwent a culture protocol that normally leads to predominant (∼90%) differentiation to ODCs. However, in the presence of the exosomes from untreated or IL-1β-treated U87 cells, significantly more cells differentiated into astrocytes, especially in the presence of exosomes obtained from the IL-1β-challenged glioma cells. Moreover, glioma-derived exosomes appeared to inhibit rNSC differentiation into ODCs or astrocytes as indicated by a significantly increased population of unlabeled cells. A portion of the resulting astrocytes coexpressed both CD133 and glial fibrillary acidic protein (GFAP) suggesting that exosomes from U87 cells could promote astrocytic differentiation of NSCs with features expected from a transformed cell. Our data clearly demonstrated that exosomes secreted by human glioma cells provide a strong driving force for rat neural stem cells to differentiate into astrocytes, uncovering potential pathways and therapeutic targets that might control this aggressive tumor type

Accurate mitochondrial DNA sequencing using off-target reads provides a single test to identify pathogenic point mutations.

PURPOSE: Mitochondrial disorders are a common cause of inherited metabolic disease and can be due to mutations affecting mitochondrial DNA or nuclear DNA. The current diagnostic approach involves the targeted resequencing of mitochondrial DNA and candidate nuclear genes, usually proceeds step by step, and is time consuming and costly. Recent evidence suggests that variations in mitochondrial DNA sequence can be obtained from whole-exome sequence data, raising the possibility of a comprehensive single diagnostic test to detect pathogenic point mutations. METHODS: We compared the mitochondrial DNA sequence derived from off-target exome reads with conventional mitochondrial DNA Sanger sequencing in 46 subjects. RESULTS: Mitochondrial DNA sequences can be reliably obtained using three different whole-exome sequence capture kits. Coverage correlates with the relative amount of mitochondrial DNA in the original genomic DNA sample, heteroplasmy levels can be determined using variant and total read depths, and-providing there is a minimum read depth of 20-fold-rare sequencing errors occur at a rate similar to that observed with conventional Sanger sequencing. CONCLUSION: This offers the prospect of using whole-exome sequence in a diagnostic setting to screen not only all protein coding nuclear genes but also all mitochondrial DNA genes for pathogenic mutations. Off-target mitochondrial DNA reads can also be used to assess quality control and maternal ancestry, inform on ethnic origin, and allow genetic disease association studies not previously anticipated with existing whole-exome data sets

TP53 mutant MDM2-amplified cell lines selected for resistance to MDM2-p53 binding antagonists retain sensitivity to ionizing radiation

Non-genotoxic reactivation of the p53 pathway by MDM2-p53 binding antagonists is an attractive treatment strategy for wild-type TP53 cancers. To determine how resistance to MDM2/p53 binding antagonists might develop, SJSA-1 and NGP cells were exposed to growth inhibitory concentrations of chemically distinct MDM2 inhibitors, Nutlin-3 and MI-63, and clonal resistant cell lines generated. The p53 mediated responses of parental and resistant cell lines were compared. In contrast to the parental cell lines, p53 activation by Nutlin-3, MI-63 or ionizing radiation was not observed in either the SJSA-1 or the NGP derived cell lines. An identical TP53 mutation was subsequently identified in both of the SJSA-1 resistant lines, whilst one out of three identified mutations was common to both NGP derived lines. Mutation specific PCR revealed these mutations were present in parental SJSA-1 and NGP cell populations at a low frequency. Despite cross-resistance to a broad panel of MDM2/p53 binding antagonists, these MDM2-amplified and TP53 mutant cell lines remained sensitive to ionizing radiation (IR). These results indicate that MDM2/p53 binding antagonists will select for p53 mutations present in tumours at a low frequency at diagnosis, leading to resistance, but such tumours may nevertheless remain responsive to alternative therapies, including IR

Clinical and cost-effectiveness of a diabetes education and behavioural weight management programme versus a diabetes education programme in adults with a recent diagnosis of type 2 diabetes: study protocol for the Glucose Lowering through Weight management (GLoW) randomised controlled trial

Introduction: People with type 2 diabetes (T2D) can improve glycaemic control or even achieve remission through weight loss and reduce their use of medication and risk of cardiovascular disease. The Glucose Lowering through Weight management (GLoW) trial will evaluate whether a tailored diabetes education and behavioural weight management programme (DEW) is more effective and cost-effective than a diabetes education (DE) programme in helping people with overweight or obesity and a recent diagnosis of T2D to lower their blood glucose, lose weight and improve other markers of cardiovascular risk. Methods and analysis: This study is a pragmatic, randomised, single-blind, parallel group, two-arm, superiority trial. We will recruit 576 adults with body mass index>25 kg/m2 and diagnosis of T2D in the past 3 years and randomise them to a tailored DEW or a DE programme. Participants will attend measurement appointments at a local general practitioner practice or research centre at baseline, 6 and 12 months. The primary outcome is 12-month change in glycated haemoglobin. The effect of the intervention on the primary outcome will be estimated and tested using a linear regression model (analysis of covariance) including randomisation group and adjusted for baseline value of the outcome and the randomisation stratifiers. Participants will be included in the group to which they were randomised, under the intention-to-treat principle. Secondary outcomes include 6-month and 12-month changes in body weight, body fat percentage, systolic and diastolic blood pressure and lipid profile; probability of achieving good glycaemic control; probability of achieving remission from diabetes; probability of losing 5% and 10% body weight and modelled cardiovascular risk (UKPDS). An intention-to-treat within-trial cost-effectiveness analysis will be conducted from NHS and societal perspectives using participant-level data. Qualitative interviews will be conducted with participants to understand why and how the programme achieved its results and how participants manage their weight after the programme ends. Ethics and dissemination: Ethical approval was received from East of Scotland Research Ethics Service on 15 May 2018 (18/ES/0048). This protocol (V.3) was approved on 19 June 2019. Findings will be published in peer-reviewed scientific journals and communicated to other stakeholders as appropriate. Trial registration number: ISRCTN18399564

Forgiveness-Reconciliation and Communication-Conflict-Resolution Interventions Versus Retested Controls in Early Married Couples

The first 6 months of marriage are optimal for marriage enrichment interventions. The Hope-Focused Approach to couple enrichment was presented as two 9-hr interventions--(a) Handling Our Problems Effectively (HOPE), which emphasized communication and conflict resolution, and (b) Forgiveness and Reconciliation through Experiencing Empathy (FREE). HOPE and FREE were compared with repeated assessment controls. Couples were randomly assigned and were assessed at pretreatment (t1); 1 month posttreatment (t2) and at 3- (t3), 6- (t4), and 12-month (t5) follow-ups using self-reports. In addition to self-report measures, couples were assessed at t1, t2, and t5 using salivary cortisol, and behavioral coding of decision making. Of 179 couples who began the study, 145 cases were analyzed. Both FREE and HOPE produced lasting positive changes on self-reports. For cortisol reactivity, HOPE and FREE reduced reactivity at t2, but only HOPE at t5. For coded behaviors, control couples deteriorated; FREE and HOPE did not change. Enrichment training was effective regardless of the focus of the training

JWST Imaging of the Cartwheel Galaxy Reveals Dust Associated with SN 2021afdx

We present near- and mid-infrared (0.9-18 $\mu$m) photometry of supernova (SN) 2021afdx, which was imaged serendipitously with the James Webb Space Telescope (JWST) as part of its Early Release Observations of the Cartwheel Galaxy. Our ground-based optical observations show it is likely to be a Type IIb SN, the explosion of a yellow supergiant, and its infrared spectral energy distribution (SED) $\approx$200 days after explosion shows two distinct components, which we attribute to hot ejecta and warm dust. By fitting models of dust emission to the SED, we derive a dust mass of $(3.8_{-0.3}^{+0.5}) \times 10^{-3}\ M_\odot$, which is the highest yet observed in a Type IIb SN but consistent with other Type II SNe observed by the Spitzer Space Telescope. We also find that the radius of the dust is significantly larger than the radius of the ejecta, as derived from spectroscopic velocities during the photospheric phase, which implies that we are seeing an infrared echo off of preexisting dust in the progenitor environment, rather than dust newly formed by the SN. Our results show the power of JWST to address questions of dust formation in SNe, and therefore the presence of dust in the early universe, with much larger samples than have been previously possible.Comment: updated to match accepted versio