Downregulation of DAX-1 Expression via miRNA Overexpression as a Mechanism to Potentiate Breast Cancer

The orphan nuclear receptor DAX-1 (Dosage Sensitive Sex Reversal, Adrenal Hypoplasia Congenita, critical region on the X chromosome, gene 1) plays a key role in mammalian sex determination and steroidogenesis. In addition to these canonical examples, DAX-1 has been shown to play a contradictory role in cancer development. While DAX-1 is overexpressed in lung and prostate cancer, it is downregulated in breast cancer. One of the explanations for the paradoxical role of DAX-1 in cancer development could be microRNA (miRNA) dysregulation. After broadly surveying over 96 miRNAs historically upregulated in MCF7 breast cancer cells, we compared the expression of DAX-1 in MCF7 and MCF10A (normal breast epithelial) cells with the presence of specific miRNA inhibitors. Our primary hypothesis remains that multiple miRNAs negatively regulate the expression of DAX-1 in human breast cancer cells and are not overexpressed in normal breast cells, providing another mechanism of lifting the repression of DAX-1 expression. Quantitative PCR and western blot analysis was performed indicating that miRNA-29b, 100, 199a, and 424 all downregulate DAX-1 expression. Similar techniques were explored to determine that miR-20b and miR-22 inhibition downregulates Estrogen Receptor α expression whereas miR-29b, 29c, and 424 inhibition indicates Cyclin D1 underexpression. Finally, we examined the migratory properties of MCF7 cells following miRNA inhibition via scratch-and-heal assays. This research will allow clinicians to screen for miRNAs that are elevated in BC patients substantially increasing the number of people diagnosed with breast cancer early on, and it will provide another method for diagnosing breast cancer or those who do not have access to preventative care

The Link Between Insecure Attachment and Depression: Two Potential Pathways

A wealth of research demonstrates a strong link between insecure attachment and depressive symptoms. However, thus far no work has discerned different pathways to depression for each of the insecure subtypes: anxious and avoidant attachment. This work looks at the behaviors that couples engage in during a conflict interaction as a potential mediator for the attachment-depression relationship, with different behaviors mediating the link between anxious and avoidant attachment and depression. For anxiously attached individuals, it was predicted that lack of support and response from the partner (actual or perceived) would account for the relationship between their attachment and depressive symptoms. While for avoidant individuals, it was predicted that partners’ hostile behaviors would account for a positive association between attachment and depression, but humor and relationship-enhancing behaviors would account for a negative association between attachment and depression. Results from this work indicated that for anxiously attached women, their perceptions of their partners’ responsiveness and their partners’ actual hostility mediated the link between their attachment and depressive symptoms

Correspondence Between Change in Adult Attachment Patterns and Change in Depression Symptoms in Early Marriage

Countless studies have demonstrated the association between attachment styles and depressive symptoms; however, thus far, none have examined concurrent change. That is, does change in attachment style predict change in depressive symptoms over time? This question was examined in a sample of 229 heterosexual newlywed couples from Western Massachusetts. It was found that changes in attachment avoidance in particular predicted changes in depressive and anxious symptoms over time. Being a parent also played a role in participants\u27 overall attachment styles, depressive symptoms and anxious symptoms on average, with differences observed by gender. Implications and suggestions for future research are discussed

Parents\u27 Value of Play in Early Childhood: A Comparative Study of Spousal Play Beliefs

Play is a vital tool for developmental growth and learning in early childhood. However, with the current focus on academics, there is less emphasis placed on encouraging children to play. The current study investigated parental beliefs on play. The sample consisted of 34 middle-class couples (34 mothers, 34 fathers) co-parenting a preschool-aged child (3-5 years) attending the laboratory school of a large mid-Atlantic university. Participants were surveyed about their beliefs on play. Results revealed mothers\u27 value of play to be higher than fathers\u27. Although significantly different, both mothers and fathers perceived play positively. The findings suggest that early childhood professionals need to further advocate the importance of quality play and its ties with academic achievement to all parents, especially those from lower socioeconomic backgrounds.;Keywords: play, belief, parent, academics, early childhood

Dysfunctional Attitudes and Low Self-Esteem Mediate the Effect of Attachment Anxiety Priming on Depression

Previous studies regarding the relationship between attachment anxiety and depression and the mediating roles of dysfunctional attitudes and self-esteem have been correlational in nature. The current study used an experimental design to look at these relationships. Attachment style was determined using a shortened version of the Experiences in Close Relationships Scale, and then either secure attachment, anxious attachment, or a control of grocery shopping was primed by instructing participants to write about one of the three scenarios. Dysfunctional attitudes were assessed, followed by state self-esteem and then state depression. Multiple regression analyses revealed that trait attachment anxiety and the anxiety prime predict dysfunctional attitudes, which in turn predict state-self esteem. Finally, state-self esteem predicted state depression and rendered previously significant associations between attachment anxiety, avoidance, anxiety priming, dysfunctional attitudes and depression insignificant when included in the analysis

Diverse response of shallow lake water levels to decadal weather patterns in a heterogeneous glacial Boreal Plains landscape

To examine the relative controls of landscape and climate on spatial variability, we measured water level dynamics of shallow lakes over two decades that represent both the heterogeneity of surficial geology classifications, and thus the potential range in surface and groundwater connectivity, and the long‐term weather patterns of the Boreal Plain hydrogeoclimatic setting. Large ranges in shallow lakes water levels (between 0.25 and 2 m) were observed corresponding to extremes in precipitation relative to the long‐term mean precipitation over the study period. We found low concurrence in water level dynamics among four detailed study lakes that received the same meteorological weather signal, but were located in different surficial geology texture classifications that incorporated important landscape parameters associated with lake water balance and storage. Surficial geology classification alone did not, however, distinguish between different ranges in lake water level measured in a broader synoptic survey of 26 lakes across the region. Thus, simple surficial geology classifications cannot alone be applied to classify Boreal Plain lake water level dynamics and other controls, notably landscape position, must also be considered. We further show that inter‐annual variability in lake water levels was significantly greater than seasonal variability in this hydrogeoclimatic setting. This emphasizes the need for studies of sufficient length to capture weather extremes that include periods of wetting and drying, and demonstrates how observed magnitudes of water level variability, and lake function, can be an artefact of study length and initiation date. These findings provide a foundation to test and calibrate conceptual understanding of the wider controls of lake water levels to form holistic frameworks to mitigate ecological and societal impacts due to hydrological changes under climate and anthropogenic disturbance within and between hydrogeoclimatic settings

Deaths from cardiovascular disease involving anticoagulants: a systematic synthesis of coroners' case reports

Background The global burden of cardiovascular disease (CVD) is forecast to increase, and anticoagulants will remain important medicines for its management. Coroners' Prevention of Future Death reports (PFDs) provide valuable insights that may enable safer and more effective use of these agents. Aim To identify CVD-related PFDs involving anticoagulants. Design & setting Case series of coronial reports in England and Wales between 2013 and 2019. Method A total of 3037 PFDs were screened for eligibility. PFDs were included where CVD and an anticoagulant caused or contributed to the death. Included cases were descriptively analysed and content analysis was used to assess concerns raised by coroners and who had responded to them. Results The study identified 113 CVD-related PFDs involving anticoagulants. Warfarin (36%, n = 41), enoxaparin (11%, n = 12), and rivaroxaban (11%, n = 12) were the most common anticoagulants reported. Concerns most frequently raised by coroners included poor systems (31%), poor communication (25%), and failures to keep accurate medical records (25%). These concerns were most often directed to NHS trusts (29%), hospitals (10%), and general practices (8%). Nearly two-thirds (60%) of PFDs had not received responses from such organisations, which are mandatory under regulation 28 of the Coroners' (Investigations) Regulations 2013. A publicly available tool has been created by the authors (https://preventabledeathstracker.net), which displays coroners’ reports in England and Wales to streamline access, and identify important lessons to prevent future deaths. Conclusion National organisations, healthcare professionals, and prescribers should take actions to address the concerns of coroners in PFDs to improve the safe use of anticoagulants in patients with CVD

Eye Tracking Reveals Impaired Attentional Disengagement Associated with Sensory Response Patterns in Children with Autism

This study used a gap-overlap paradigm to examine the impact of distractor salience and temporal overlap on the ability to disengage and orient attention in 50 children (4–13 years) with ASD, DD and TD, and associations between attention and sensory response patterns. Results revealed impaired disengagement and orienting accuracy in ASD. Disengagement was impaired across all groups during temporal overlap for dynamic stimuli compared to static, but only ASD showed slower disengagement from multimodal relative to unimodal dynamic stimuli. Attentional disengagement had differential associations with distinct sensory response patterns in ASD and DD. Atypical sensory processing and temporal binding appear to be intertwined with development of disengagement in ASD, but longitudinal studies are needed to unravel causal pathways

A complete characterization of phase space measurements

We characterize all the phase space measurements for a non-relativistic particle.Comment: 11 pages, latex, no figures, iopart styl