An Explanation of the Enactment of Nonconsensual Pornography Policies within States: External and Internal Pressures

Nonconsensual pornography entails the sharing of intimate images, along with personal information and details, within the Internet realm. It is commonly referred to as “revenge porn” because of its vindictive nature. Out of all 50 states, only 27 states have a policy criminalizing the distribution of nonconsensual pornography in effect. For a policy that associates Internet usage with a question of women’s rights, and a theme denoting a sexual connotation, why haven’t more states taken up efforts to enact this particular policy? I argue that the studies of policy diffusion and policy dispersion help explain the enactment of nonconsensual pornography policies. Policy diffusion involves external pressures, such as one government’s policy choices being influenced by the previous choices of other government. Policy diffusion involves internal pressures, such as attitudes of legislators or composition of the state government. In this context, two sets of internal pressures and two sets of external pressures are examined. The internal pressures include characteristics of each individual state and the evaluation of a state score that corresponds to current Internet regulation policies in effect. The external pressures include geographic clustering, which includes diffusion of policies influencing neighboring states, and analyzing the wording that relates to the degree of punishment associated with the act of distributing nonconsensual pornography. Analyzing the wording of the punishment will help draw the effect neighbor-to-neighbor flow had on the policy enactment. Exploring both internal and external pressures affecting each state allows for an in depth study into a topic not widely discussed, nonconsensual pornography, but also a better look at the rate of success in enacting a criminalization policy

Is global ozone recovering?

Thanks to the Montreal Protocol, the stratospheric concentrations of ozone-depleting chlorine and bromine have been declining since their peak in the late 1990s. Global ozone has responded: The substantial ozone decline observed since the 1960s ended in the late 1990s. Since then, ozone levels have remained low, but have not declined further. Now general ozone increases and a slow recovery of the ozone layer is expected. The clearest signs of increasing ozone, so far, are seen in the upper stratosphere and for total ozone columns above Antarctica in spring. These two regions had also seen the largest ozone depletions in the past. Total column ozone at most latitudes, however, does not show clear increases yet. This is not unexpected, because the removal of chlorine and bromine from the stratosphere is three to four times slower than their previous increase. Detecting significant increases in total column ozone, therefore, will require much more time than the detection of its previous decline. The search is complicated by variations in ozone that are not caused by declining chlorine or bromine, but are due, e.g., to transport changes in the global Brewer–Dobson circulation. Also, very accurate observations are necessary to detect the expected small increases. Nevertheless, observations and model simulations indicate that the stratosphere is on the path to ozone recovery. This recovery process will take many decades. As chlorine and bromine decline, other factors will become more important. These include climate change and its effects on stratospheric temperatures, changes in the Brewer–Dobson circulation (both due to increasing CO2), increasing emissions of trace gases like N2O, CH4, possibly large future increases of short-lived substances (like CCl2H2) from both natural and anthropogenic sources, and changes in tropospheric ozone

Age groups that sustain resurging COVID-19 epidemics in the United States

After initial declines, in mid-2020 a resurgence in transmission of novel coronavirus disease (COVID-19) occurred in the United States and Europe. As efforts to control COVID-19 disease are reintensified, understanding the age demographics driving transmission and how these affect the loosening of interventions is crucial. We analyze aggregated, age-specific mobility trends from more than 10 million individuals in the United States and link these mechanistically to age-specific COVID-19 mortality data. We estimate that as of October 2020, individuals aged 20 to 49 are the only age groups sustaining resurgent SARS-CoV-2 transmission with reproduction numbers well above one and that at least 65 of 100 COVID-19 infections originate from individuals aged 20 to 49 in the United States. Targeting interventions-including transmission-blocking vaccines-to adults aged 20 to 49 is an important consideration in halting resurgent epidemics and preventing COVID-19-attributable deaths

Novel insights into the mechanisms mediating the local antihypertrophic effects of cardiac atrial natriuretic peptide: role of cGMP-dependent protein kinase and RGS2

Cardiac atrial natriuretic peptide (ANP) locally counteracts cardiac hypertrophy via the guanylyl cyclase-A (GC-A) receptor and cGMP production, but the downstream signalling pathways are unknown. Here, we examined the influence of ANP on β-adrenergic versus Angiotensin II (Ang II)-dependent (Gs vs. Gαq mediated) modulation of Ca2+i-handling in cardiomyocytes and of hypertrophy in intact hearts. L-type Ca2+ currents and Ca2+i transients in adult isolated murine ventricular myocytes were studied by voltage-clamp recordings and fluorescence microscopy. ANP suppressed Ang II-stimulated Ca2+ currents and transients, but had no effect on isoproterenol stimulation. Ang II suppression by ANP was abolished in cardiomyocytes of mice deficient in GC-A, in cyclic GMP-dependent protein kinase I (PKG I) or in the regulator of G protein signalling (RGS) 2, a target of PKG I. Cardiac hypertrophy in response to exogenous Ang II was significantly exacerbated in mice with conditional, cardiomyocyte-restricted GC-A deletion (CM GC-A KO). This was concomitant to increased activation of the Ca2+/calmodulin-dependent prohypertrophic signal transducer CaMKII. In contrast, β-adrenoreceptor-induced hypertrophy was not enhanced in CM GC-A KO mice. Lastly, while the stimulatory effects of Ang II on Ca2+-handling were absent in myocytes of mice deficient in TRPC3/TRPC6, the effects of isoproterenol were unchanged. Our data demonstrate a direct myocardial role for ANP/GC-A/cGMP to antagonize the Ca2+i-dependent hypertrophic growth response to Ang II, but not to β-adrenergic stimulation. The selectivity of this interaction is determined by PKG I and RGS2-dependent modulation of Ang II/AT1 signalling. Furthermore, they strengthen published observations in neonatal cardiomyocytes showing that TRPC3/TRPC6 channels are essential for Ang II, but not for β-adrenergic Ca2+i-stimulation in adult myocytes

Diametrically opposite methylome-transcriptome relationships in high- and low-CpG promoter genes in postmitotic neural rat tissue

DNA methylation can control some CpG-poor genes but unbiased studies have not found a consistent genome-wide association with gene activity outside of CpG islands or shores possibly due to use of cell lines or limited bioinformatics analyses. We performed reduced representation bisulfite sequencing (RRBS) of rat dorsal root ganglia encompassing postmitotic primary sensory neurons (n = 5, r > 0.99; orthogonal validation p < 10−19). The rat genome suggested a dichotomy of genes previously reported in other mammals: low CpG content (< 3.2%) promoter (LCP) genes and high CpG content (≥ 3.2%) promoter (HCP) genes. A genome-wide integrated methylome-transcriptome analysis showed that LCP genes were markedly hypermethylated when repressed, and hypomethylated when active with a 40% difference in a broad region at the 5′ of the transcription start site (p < 10−87 for -6000 bp to -2000 bp, p < 10−73 for -2000 bp to +2000 bp, no difference in gene body p = 0.42). HCP genes had minimal TSS-associated methylation regardless of transcription status, but gene body methylation appeared to be lost in repressed HCP genes. Therefore, diametrically opposite methylome-transcriptome associations characterize LCP and HCP genes in postmitotic neural tissue in vivo

Monthly intravenous methylprednisolone in relapsing-remitting multiple sclerosis - reduction of enhancing lesions, T2 lesion volume and plasma prolactin concentrations

BACKGROUND: Intravenous methylprednisolone (IV-MP) is an established treatment for multiple sclerosis (MS) relapses, accompanied by rapid, though transient reduction of gadolinium enhancing (Gd+) lesions on brain MRI. Intermittent IV-MP, alone or with immunomodulators, has been suggested but insufficiently studied as a strategy to prevent relapses. METHODS: In an open, single-cross-over study, nine patients with relapsing-remitting MS (RR-MS) underwent cranial Gd-MRI once monthly for twelve months. From month six on, they received a single i.v.-infusion of 500 mg methylprednisolone (and oral tapering for three days) after the MRI. Primary outcome measure was the mean number of Gd+ lesions during treatment vs. baseline periods; T2 lesion volume and monthly plasma concentrations of cortisol, ACTH and prolactin were secondary outcome measures. Safety was assessed clinically, by routine laboratory and bone mineral density measurements. Soluble immune parameters (sTNF-RI, sTNF-RII, IL1-ra and sVCAM-1) and neuroendocrine tests (ACTH test, combined dexamethasone/CRH test) were additionally analyzed. RESULTS: Comparing treatment to baseline periods, the number of Gd+ lesions/scan was reduced in eight of the nine patients, by a median of 43.8% (p = 0.013, Wilcoxon). In comparison, a pooled dataset of 83 untreated RR-MS patients from several studies, selected by the same clinical and MRI criteria, showed a non-significant decrease by a median of 14% (p = 0.32). T2 lesion volume decreased by 21% during treatment (p = 0.001). Monthly plasma prolactin showed a parallel decline (p = 0.027), with significant cross-correlation with the number of Gd+ lesions. Other hormones and immune system variables were unchanged, as were ACTH test and dexamethasone-CRH test. Treatment was well tolerated; routine laboratory and bone mineral density were unchanged. CONCLUSION: Monthly IV-MP reduces inflammatory activity and T2 lesion volume in RR-MS

Global Reorganization of Replication Domains During Embryonic Stem Cell Differentiation

DNA replication in mammals is regulated via the coordinate firing of clusters of replicons that duplicate megabase-sized chromosome segments at specific times during S-phase. Cytogenetic studies show that these “replicon clusters” coalesce as subchromosomal units that persist through multiple cell generations, but the molecular boundaries of such units have remained elusive. Moreover, the extent to which changes in replication timing occur during differentiation and their relationship to transcription changes has not been rigorously investigated. We have constructed high-resolution replication-timing profiles in mouse embryonic stem cells (mESCs) before and after differentiation to neural precursor cells. We demonstrate that chromosomes can be segmented into multimegabase domains of coordinate replication, which we call “replication domains,” separated by transition regions whose replication kinetics are consistent with large originless segments. The molecular boundaries of replication domains are remarkably well conserved between distantly related ESC lines and induced pluripotent stem cells. Unexpectedly, ESC differentiation was accompanied by the consolidation of smaller differentially replicating domains into larger coordinately replicated units whose replication time was more aligned to isochore GC content and the density of LINE-1 transposable elements, but not gene density. Replication-timing changes were coordinated with transcription changes for weak promoters more than strong promoters, and were accompanied by rearrangements in subnuclear position. We conclude that replication profiles are cell-type specific, and changes in these profiles reveal chromosome segments that undergo large changes in organization during differentiation. Moreover, smaller replication domains and a higher density of timing transition regions that interrupt isochore replication timing define a novel characteristic of the pluripotent state