Expression Of Oct4, Cdx2 And Yap1 During Blastocyst Formation In The Marsupial, Monodelphis Domestica

The marsupial blastocyst first forms as a simple epithelium securely adherent to the zona pellucida. It has no inner cell mass (ICM), which in the eutherian (mouse) blastocyst contains the embryonic stem cells at this stage. The marsupial ICM equivalent, the pluriblast, is co-planar with the trophoblast. By contrast, the mouse trophoblast encloses the ICM. Oct4, Cdx2 and Yap1 play crucial roles in allocating mouse blastocyst cells to either trophoblast or ICM fates. Because these genes are found in the opossum genome, we hypothesized that they may have a similar role in cell allocation between pluriblast and trophoblast in the opossum blastocyst. In both mouse and opossum, Oct4 is expressed in all embryonic cells prior to blastocyst formation. During mouse blastocyst formation, Cdx2 is upregulated as Oct4 is downregulated in the nascent trophoblast. In the opossum, a patch of cells in the unilaminar blastocyst epithelium (pluriblast) undergoes the same switch in gene expression. In both types of embryos, Yap1 is translocated to the nuclei of putative trophoblast cells but remains in the cytoplasm of cells fated to be ICM or pluriblast. Our results indicate that the roles of Oct4, Cdx2 and Yap1 in allocating cells to the trophoblast lineage are evolutionarily conserved between marsupials and eutherians, despite the topological differences between their blastocysts. Our results also suggest that cell position plays less of a role in mammalian trophoblast differentiation as has been long believed

Digital phenotyping of complex psychological responses to the COVID-19 pandemic

Background: The novel coronavirus disease 2019 (COVID-19) has negatively impacted mortality, economic conditions, and mental health. A large scale study on psychological reactions to the pandemic to inform ongoing population-level symptom tracking and response to treatment is currently lacking. Methods: Average intake scores for standard depression and anxiety symptom scales were tracked from January 1, 2017 to June 9, 2020 for patients seeking treatment from a digital mental health service to gauge the relationship between COVID-19 and self-reported symptoms. We applied natural language processing (NLP) to unstructured therapy transcript data from patients seeking treatment during the height of the pandemic in the United States between March 1, 2020 and June 9, 2020 to identify words associated with COVID-19 mentions. This analysis was used to identify symptoms that were present beyond those assessed by standard depression and anxiety measures. Results: Depression and anxiety symptoms reported by 169,889 patients between January 1, 2017 and June 9, 2020 were identified. There was no detectable change in intake depression symptom scores. Intake anxiety symptom scores increased 1.42 scale points [95% CI: 1.18, 1.65] between March 15, 2020 and April 1, 2020, when scores peaked. In the transcript data of these 169,889 patients, plus an expanded sample of 49,267 patients without symptom reports, term frequency-inverse document frequency (tf-idf) identified 2,377 positively correlated and 661 negatively correlated terms that were significantly (FDR<.01) associated with mentions of the virus. These terms were classifiable into 24 symptoms beyond those included in the diagnostic criteria for anxiety or depression. Conclusions: The COVID-19 pandemic may have increased intake anxiety symptoms for individuals seeking digital mental health treatment. NLP analyses suggest that standard symptom scales for depression and anxiety alone are inadequate to fully assess and track psychological reactions to the pandemic. Symptoms of grief, trauma, obsession-compulsion, agoraphobia, hypochondriasis, panic, and non- suicidal self-injury should be monitored as part of a new COVID-19 Syndrome category

Complex psychological responses to the COVID-19 pandemic: Digital phenotyping evidence from a large telemental health platform (Preprint)

BackgroundThe novel COVID-19 disease has negatively impacted mortality, economic conditions, and mental health. These impacts are likely to continue after the COVID-19 pandemic ends. There are no methods for characterizing the mental health burden of the COVID-19 pandemic, and differentiating this burden from that of the prepandemic era. Accurate illness detection methods are critical for facilitating pandemic-related treatment and preventing the worsening of symptoms.ObjectiveWe aimed to identify major themes and symptom clusters in the SMS text messages that patients send to therapists. We assessed patients who were seeking treatment for pandemic-related distress on Talkspace, which is a popular telemental health platform.MethodsWe used a machine learning algorithm to identify patients' pandemic-related concerns, based on their SMS text messages in a large, digital mental health service platform (ie, Talkspace). This platform uses natural language processing methods to analyze unstructured therapy transcript data, in parallel with brief clinical assessment methods for analyzing depression and anxiety symptoms.ResultsOur results show a significant increase in the incidence of COVID-19-related intake anxiety symptoms (P<.001), but no significant differences in the incidence of intake depression symptoms (P=.79). During our transcript analyses, we identified terms that were related to 24 symptoms outside of those included in the diagnostic criteria for anxiety and depression.ConclusionsOur findings for Talkspace suggest that people who seek treatment during the pandemic experience more severe intake anxiety than they did before the COVID-19 outbreak. It is important to monitor the symptoms that we identified in this study and the symptoms of anxiety and depression, to fully understand the effects of the COVID-19 pandemic on mental health

Expression patterns of Oct4, Cdx2, Tead4, and Yap1 proteins during blastocyst formation in embryos of the marsupial, Monodelphis domestica Wagner

The marsupial blastocyst forms in an entirely different manner from its eutherian counterpart, involving cell–zona rather than cell–cell adhesion during the 8- to-16-cell transition. While the eutherian blastocyst consists of a spherical trophoblast completely enveloping a pluripotent inner cell mass, or pluriblast, the marsupial blastocyst forms initially as a bowl-shaped monolayer of cells lining the zona pellucida at the embryonic pole (ep). This monolayer contains a small patch of centrally positioned pluriblast cells edged with trophoblast cells that later coalesce at the abembryonic pole. Using immunocytochemistry, we examined the localization of the proteins Oct4, Cdx2, Tead4, Sox2, and Yap1 in opossum embryos to determine if their temporal expression pattern differed from that in the mouse, given the important differences in cell behavior preceding blastocyst formation in these mammals. Our results indicate that these proteins are expressed in similar temporal patterns despite the topological differences between mouse and opossum cleavage-stage embryos and blastocysts. That the Hippo-pathway protein Yap1 localized specifically around the approximately 128-cell stage to opossum trophoblast nuclei but remained in the cytoplasm of pluriblast cells suggests that this transcriptional regulator participates in allocating cells to the trophoblast lineage, as it does in mouse. Interestingly, in both mouse and opossum embryos, expression of the pluripotency marker Oct4 persisted after Cdx2, which signals trophoblast specification, began to be expressed in trophoblast cells. This and the observation that Cdx2 is present in opossum embryos well before blastomere–zona adhesion even occurs suggests that the proteins studied may have other roles in early mammalian embryonic development