The Gut Microbiome Is Altered in a Letrozole-Induced Mouse Model of Polycystic Ovary Syndrome.

Women with polycystic ovary syndrome (PCOS) have reproductive and metabolic abnormalities that result in an increased risk of infertility, diabetes and cardiovascular disease. The large intestine contains a complex community of microorganisms (the gut microbiome) that is dysregulated in humans with obesity and type 2 diabetes. Using a letrozole-induced PCOS mouse model, we demonstrated significant diet-independent changes in the gut microbial community, suggesting that gut microbiome dysbiosis may also occur in PCOS women. Letrozole treatment was associated with a time-dependent shift in the gut microbiome and a substantial reduction in overall species and phylogenetic richness. Letrozole treatment also correlated with significant changes in the abundance of specific Bacteroidetes and Firmicutes previously implicated in other mouse models of metabolic disease in a time-dependent manner. Our results suggest that the hyperandrogenemia observed in PCOS may significantly alter the gut microbiome independently of diet

Constitutively active FOXO1 diminishes activin induction of Fshb transcription in immortalized gonadotropes.

In the present study, we investigate whether the FOXO1 transcription factor modulates activin signaling in pituitary gonadotropes. Our studies show that overexpression of constitutively active FOXO1 decreases activin induction of murine Fshb gene expression in immortalized LβT2 cells. We demonstrate that FOXO1 suppression of activin induction maps to the -304/-95 region of the Fshb promoter containing multiple activin response elements and that the suppression requires the FOXO1 DNA-binding domain (DBD). FOXO1 binds weakly to the -125/-91 region of the Fshb promoter in a gel-shift assay. Since this region of the promoter contains a composite SMAD/FOXL2 binding element necessary for activin induction of Fshb transcription, it is possible that FOXO1 DNA binding interferes with SMAD and/or FOXL2 function. In addition, our studies demonstrate that FOXO1 directly interacts with SMAD3/4 but not SMAD2 in a FOXO1 DBD-dependent manner. Moreover, we show that SMAD3/4 induction of Fshb-luc and activin induction of a multimerized SMAD-binding element-luc are suppressed by FOXO1 in a DBD-dependent manner. These results suggest that FOXO1 binding to the proximal Fshb promoter as well as FOXO1 interaction with SMAD3/4 proteins may result in decreased activin induction of Fshb in gonadotropes

A cultural exploration of the social media manipulators

The widespread use of Internet social media sites for the production and dissemination of propaganda continues to grow and gather attention. Social media sites spread information faster and wider than those institutions and methods historically limited to state-affiliated organizations. There are several characteristics that are unique to virtual space and make the production and dissemination of propaganda different; they include the Internet’s global reach, the recipient’s apparent trust placed in information source as well as the information sources, and the low cost of participation. Thus, the use of social media as a method to spread misleading information exploits trust relationships between the reader and the source. Although propaganda is a weapon with a long history in war, in the 21st century, the delivery and distribution of propaganda through the trusted channel of social media is markedly different than what was historically observed. We investigated the relationships among state-affiliated actors who use social media to produce and distribute propaganda along with their national cultural values. Prior research inferred a link between culture and social media usage (Hofstede et al., 2010; Sample & Karamanian 2014). Specifically, Hofstede et al. (2010) contended that cultures that are more masculine use the Internet for information seeking, whereas more feminine-oriented cultures use social media sites for sharing information, seeking to build better “trusting” relationships. We sought to explore whether masculine countries would leverage the trust relationships that are present with social media users to further the reach of state-affiliated propaganda. We built upon Bradshaw & Howard’s (2017) study on propaganda purveyors, which examined preferred social media deployment techniques across 29 different countries. Using previously published methods, we examined associations with culture using Hofestede’s scale. Since masculine countries have previously been associated with information-seeking behaviors, we sought to explore the potential that more masculine cultural values are associated with greater information-shaping and -distributing behaviors compared with more feminine cultural values. The results showed a strong difference in distributions, countries that deployed fake news via social media tended to have more masculine cultural values. Moderate differences were observed in other cultural values, purveyors of social media propaganda exhibited more authoritarianism and uncertainty avoidance. These findings suggest that specific cultural values associate with the distrubtion of fake news, indicating that culturally aware responses may be more effective when responding to these events

Collateral donor artery physiology and the influence of a chronic total occlusion on fractional flow reserve

Background— The presence of a concomitant chronic total coronary occlusion (CTO) and a large collateral contribution might alter the fractional flow reserve (FFR) of an interrogated vessel, rendering the FFR unreliable at predicting ischemia should the CTO vessel be revascularized and potentially affecting the decision on optimal revascularization strategy. We tested the hypothesis that donor vessel FFR would significantly change after percutaneous coronary intervention of a concomitant CTO. Methods and Results— In consecutive patients undergoing percutaneous coronary intervention of a CTO, coronary pressure and flow velocity were measured at baseline and hyperemia in proximal and distal segments of both nontarget vessels, before and after percutaneous coronary intervention. Hemodynamics including FFR, absolute coronary flow, and the coronary flow velocity–pressure gradient relation were calculated. After successful percutaneous coronary intervention in 34 of 46 patients, FFR in the predominant donor vessel increased from 0.782 to 0.810 (difference, 0.028 [0.012 to 0.044]; P=0.001). Mean decrease in baseline donor vessel absolute flow adjusted for rate pressure product: 177.5 to 139.9 mL/min (difference −37.6 [−62.6 to −12.6]; P=0.005), mean decrease in hyperemic flow: 306.5 to 272.9 mL/min (difference, −33.5 [−58.7 to −8.3]; P=0.011). Change in predominant donor vessel FFR correlated with angiographic (%) diameter stenosis severity (r=0.44; P=0.009) and was strongly related to stenosis severity measured by the coronary flow velocity–pressure gradient relation (r=0.69; P<0.001). Conclusions— Recanalization of a CTO results in a modest increase in the FFR of the predominant collateral donor vessel associated with a reduction in coronary flow. A larger increase in FFR is associated with greater coronary stenosis severity

A Comparison of the Characteristic Traits of Learning Theories in the Three Synoptic Gospels by Thematic Narrative Analysis

Many writers have discussed aspects of pedagogy in connection with the books of the New Testament but few have related pedagogical elements observable in the Gospels to current theories of how people learn and the consequent teaching methods. I perform, here, a thematic narrative analysis of the synoptic gospel texts, with the focus of contemporary approaches to learning and teaching. The project aims to identify traits of pedagogic themes throughout these gospels, with a view to establishing if it is appropriate to describe any of them as characterised by one or other of the commonly recognised theories of learning. While such a characterisation is not expected to be perfect across any one Synoptic, it could prove possible to demonstrate sufficient correlation with some theoretical learning model to argue that the gospel is typified by that pedagogy. This thesis also compares and contrasts the three synoptic gospels, in respect of their emphasis on those themes. The thesis outlines the salient features of the currently prominent learning and teaching approaches and considers the applicability of each model to this investigation. The three approaches found most useful for the analysis are: that referred to as behaviourism in teaching; a cognitive, constructivist pedagogic model; and the strongly situated learning theory. The synoptic gospels are examined for aspects of those themes, where possible, as a series of parallel passages, each regarded as a bounded text segment. Special Lukan material is also considered, separately. Any reader’s interpretation of such a narrative is constructed from within their own pre-existing framework for understanding it. My reading of the Gospels here is, therefore, a personal response to the text, which has arisen from my experience working in adult education and training. The conclusion of this work is that all three synoptic gospels exhibit textual features corresponding to a specific teaching and learning model sufficiently consistently to regard them as substantially informed by it. Furthermore, the Synoptics each exemplify a different pedagogical approach. Matthew’s gospel portrays a predominantly behaviourist pedagogy, the Gospel of Mark a generally cognitivist, constructivist approach to learning and teaching and Luke the characteristics of a strongly situative learning theory. It is anticipated that the comparison presented here will provide a new contribution to the discussion of the differences between the otherwise parallel accounts evident within the first three gospels

A compendium of multi-omics data illuminating host responses to lethal human virus infections

Human infections caused by viral pathogens trigger a complex gamut of host responses that limit disease, resolve infection, generate immunity, and contribute to severe disease or death. Here, we present experimental methods and multi-omics data capture approaches representing the global host response to infection generated from 45 individual experiments involving human viruses from the Orthomyxoviridae, Filoviridae, Flaviviridae, and Coronaviridae families. Analogous experimental designs were implemented across human or mouse host model systems, longitudinal samples were collected over defined time courses, and global multi-omics data (transcriptomics, proteomics, metabolomics, and lipidomics) were acquired by microarray, RNA sequencing, or mass spectrometry analyses. For comparison, we have included transcriptomics datasets from cells treated with type I and type II human interferon. Raw multi-omics data and metadata were deposited in public repositories, and we provide a central location linking the raw data with experimental metadata and ready-to-use, quality-controlled, statistically processed multi-omics datasets not previously available in any public repository. This compendium of infection-induced host response data for reuse will be useful for those endeavouring to understand viral disease pathophysiology and network biology

Teaching Psychological Principles to Cybersecurity Students

This paper will discuss our observations gained from teaching psychological principles and methods to undergraduate and postgraduate cybersecurity students. We will draw on and extend our previous work encouraging the teaching of psychology in computing and cybersecurity education. We pay special attention to the consideration of characteristics of cybersecurity students in terms of teaching psychology in a way that will be accessible and engaging. We then discuss the development and use of an online training tool which draws on psychology to help educators and companies to raise awareness of cybersecurity risks in students and employees. Finally, we offer some practical suggestions to incorporate psychology into the cybersecurity curriculum

Modeling the OH-Initiated Oxidation of Mercury in the Global Atmosphere Without Violating Physical Laws

In 2005, Calvert and Lindberg wrote that the use of laboratory-derived rate constants for OH + Hg(0) “…to determine the extent of Hg removal by OH in the troposphere will greatly over-estimate the importance of Hg removal by this reaction.” The HOHg• intermediate formed from OH + Hg will mostly fall apart in the atmosphere before it can react. By contrast, in laboratory experiments, Calvert and Lindberg expected HOHg• to react with radicals (whose concentrations are much higher than in the atmosphere). Yet almost all models of oxidation of Hg(0) ignore the argument of Calvert and Lindberg. We present a way for modelers to include the OH + Hg reaction while accounting quantitatively for the dissociation of HOHg•. We use high levels of quantum chemistry to establish the HO-Hg bond energy as 11.0 kcal/mole, and calculate the equilibrium constant for OH + Hg = HOHg•. Using the measured rate constant for association of OH with Hg, we determine the rate constant for HOHg• dissociation. Theory is also used to demonstrate that HOHg• forms stable compounds, HOHgY, with atmospheric radicals (Y = NO2, HOO•, CH3OO•, and BrO). We then present rate constants for use in in modeling OH-initiated oxidation of Hg(0). We use this mechanism to model the global oxidation of Hg(0) in the period 2013-2015 using the GEOS-Chem 3D model of atmospheric chemistry. Because of the rapid dissociation of HOHg•, OH accounts fo