Prostitution Policy: Ending the World\u27s Oldest Profession

When it comes to prostitution, “a prostitute treats herself like a chair for someone to sit on. Her mind goes blank. She just lies there. You become just an object…After a while, it becomes just a normal thing.” As the “world’s oldest profession,” prostitution 1 permeates all countries and cultures. So for centuries, women have endured this “chair” reality, an object to service men. Most societies would point to sex work as a black mark on society, but even that is up for debate. It is unusual for any social practice to have the kind of longevity and breadth of prostitution across the globe. The magnitude and stamina of prostitution worldwide are alarming. In this paper I will look at prostitution as a whole, in order to comprehensibly understand why it is a relevant area of study. Then two drastically different policies —legalization and criminalization—will be compared in order to understand the effectiveness of each. Along with these two policies, the countries of the Netherlands and Sweden will be looked at to provide a concrete comparison of how the policies play out in reality. After a comprehensive analysis, criminalizing the demand for prostitution is a more appropriate response to prostitution than legalization, but with a few caveats. As a result of the lack of clarity from a statistical standpoint, the paper will then transition to an analysis of why prostitution in society is so harmful, looking specifically at the exploitive and inequality-promoting aspects. Overall, this paper will determine practical policy applications for prostitution in the United States, as well as prove why this Farley, “Bad for the Body”, 1106. 11 2 is a problem that needs to be addressed, and why it ought to be addressed in accordance with the policy recommendation

Social information changes stress hormone receptor expression in the songbird brain

Social information is used by many vertebrate taxa to inform decision-making, including resource-mediated movements, yet the mechanisms whereby social information is integrated physiologically to affect such decisions remain unknown. Social information is known to influence the physiological response to food reduction in captive songbirds. Red crossbills (Loxia curvirostra) that were food reduced for several days showed significant elevations in circulating corticosterone (a “stress” hormone often responsive to food limitation) only if their neighbors were similarly food restricted. Physiological responses to glucocorticoid hormones are enacted through two receptors that may be expressed differentially in target tissues. Therefore, we investigated the influence of social information on the expression of the mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNA in captive red crossbill brains. Although the role of MR and GR in the response to social information may be highly complex, we specifically predicted social information from food-restricted individuals would reduce MR and GR expression in two brain regions known to regulate hypothalamic-pituitary-adrenal (HPA) activity - given that reduced receptor expression may lessen the efficacy of negative feedback and release inhibitory tone on the HPA. Our results support these predictions - offering one potential mechanism whereby social cues could increase or sustain HPA-activity during stress. The data further suggest different mechanisms by which metabolic stress versus social information influence HPA activity and behavioral outcomes

The rapid development of a novel kidney-specific digital intervention for self-management of physical activity and emotional well-being during the COVID-19 pandemic and beyond: Kidney Beam

King's College Hospital; Kidney Research UK; Beam; National Institute for Health Research (NIHR) under (NIHR301893), (NIHR301593), and (ICA-CL-2017-03-020)

Plinabulin, an inhibitor of tubulin polymerization, targets KRAS signaling through disruption of endosomal recycling

Constitutive activation of Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most common oncogenic event in certain types of human cancer and is associated with poor patient survival. Small molecule signaling inhibitors have improved the clinical outcomes of patients with various cancer types but attempts to target KRAS have been unsuccessful. Plinabulin represents a novel class of agents that inhibit tubulin polymerization with a favorable safety profile in clinical trials. In the present study, the potency of plinabulin to inhibit tubulin polymerization and growth of KRAS-driven cancer cells was characterized. efficacy of plinabulin was tested in two different mouse models; one being the RCAS/t-va gene transfer system and the other being a xenograft model. cell culture tubulin polymerization assays were used to complement the mouse models. There was improved survival in a KRAS-driven mouse gene transfer glioma model, but lack of benefit in a similar model, without constitutively active KRAS, which supports the notion of a KRAS-specific effect. This survival benefit was mediated, at least in part, by the ability of plinabulin to inhibit tubulin polymerization and disrupt endosomal recycling. It was proposed a mechanism of compromised endosomal recycling of displaced KRAS through targeting microtubules that yields inhibition of protein kinase B, but not extracellular signal regulated kinase (ERK) signaling, therefore lending rationale to combination treatments of tubulin- and ERK-targeting agents in KRAS-driven cancer

Diversity and Complexity of the Large Surface Protein Family in the Compacted Genomes of Multiple Pneumocystis Species

Pneumocystis, a major opportunistic pathogen in patients with a broad range of immunodeficiencies, contains abundant surface proteins encoded by a multicopy gene family, termed the major surface glycoprotein (Msg) gene superfamily. This superfamily has been identified in all Pneumocystis species characterized to date, highlighting its important role in Pneumocystis biology. In this report, through a comprehensive and in-depth characterization of 459 msg genes from 7 Pneurnocystis species, we demonstrate, for the first time, the phylogeny and evolution of conserved domains in Msg proteins and provide a detailed description of the classification, unique characteristics, and phylogenetic relatedness of five Msg families. We further describe, for the first time, the relative expression levels of individual msg families in two rodent Pneumocystis species, the substantial variability of the msg repertoires in P. coda from laboratory and wild rats, and the distinct features of the expression site for the classic msg genes in Pneumocystis from 8 mammalian host species. Our analysis suggests multiple functions for this superfamily rather than just conferring antigenic variation to allow immune evasion as previously believed. This study provides a rich source of information that lays the foundation for the continued experimental exploration of the functions of the Msg superfamily in Pneumocystis biology. IMPORTANCE Pneumocystis continues to be a major cause of disease in humans with immunodeficiency, especially those with HIV/AIDS and organ transplants, and is being seen with increasing frequency worldwide in patients treated with immunode-pleting monoclonal antibodies. Annual health care associated with Pneumocystis pneumonia costs similar to$475 million dollars in the United States alone. In addition to causing overt disease in immunodeficient individuals, Pneumocystis can cause subclinical infection or colonization in healthy individuals, which may play an important role in species preservation and disease transmission. Our work sheds new light on the diversity and complexity of the msg superfamily and strongly suggests that the versatility of this superfamily reflects multiple functions, including antigenic variation to allow immune evasion and optimal adaptation to host environmental conditions to promote efficient infection and transmission. These findings are essential to consider in developing new diagnostic and therapeutic strategies.Peer reviewe

Evaluating the effect of a digital health intervention to enhance physical activity in people with chronic kidney disease (Kidney BEAM): a multicentre, randomised controlled trial in the UK

BACKGROUND: Remote digital health interventions to enhance physical activity provide a potential solution to improve the sedentary behaviour, physical inactivity, and poor health-related quality of life that are typical of chronic conditions, particularly for people with chronic kidney disease. However, there is a need for high-quality evidence to support implementation in clinical practice. The Kidney BEAM trial evaluated the clinical effect of a 12-week physical activity digital health intervention on health-related quality of life. METHODS: In a single-blind, randomised controlled trial conducted at 11 centres in the UK, adult participants (aged ≥18 years) with chronic kidney disease were recruited and randomly assigned (1:1) to the Kidney BEAM physical activity digital health intervention or a waiting list control group. Randomisation was performed with a web-based system, in randomly permuted blocks of six. Outcome assessors were masked to treatment allocation. The primary outcome was the difference in the Kidney Disease Quality of Life Short Form version 1.3 Mental Component Summary (KDQoL-SF1.3 MCS) between baseline and 12 weeks. The trial was powered to detect a clinically meaningful difference of 3 arbitrary units (AU) in KDQoL-SF1.3 MCS. Outcomes were analysed by an intention-to-treat approach using an analysis of covariance model, with baseline measures and age as covariates. The trial was registered with ClinicalTrials.gov, NCT04872933. FINDINGS: Between May 6, 2021, and Oct 30, 2022, 1102 individuals were assessed for eligibility, of whom 340 participants were enrolled and randomly assigned to the Kidney BEAM intervention group (n=173) or the waiting list control group (n=167). 268 participants completed the trial (112 in the Kidney BEAM group and 156 in the waiting list control group). All 340 randomly assigned participants were included in the intention-to treat population. At 12 weeks, there was a significant improvement in KDQoL-SF.13 MCS score in the Kidney BEAM group (from mean 44·6 AU [SD 10·8] at baseline to 47·0 AU [10·6] at 12 weeks) compared with the waiting list control group (from 46·1 AU [10·5] to 45·0 AU [10·1]; between-group difference of 3·1 AU [95% CI 1·8-4·4]; p<0·0001). INTERPRETATION: The Kidney BEAM physical activity platform is an efficacious digital health intervention to improve mental health-related quality of life in patients with chronic kidney disease. These findings could facilitate the incorporation of remote digital health interventions into clinical practice and offer a potential intervention worthy of investigation in other chronic conditions. FUNDING: Kidney Research UK

A systematic map of studies testing the relationship between temperature and animal reproduction

Funding: This work was funded by the European Society for Evolution (which funds a Special Topic Network on Evolutionary Ecology of Thermal Fertility Limits to CF, AB, RRS and TARP), the Natural Environment Research Council (NE/P002692/1 to TARP, AB and RRS, NE/X011550/1 to LRD and TARP), the Biotechnology and \Biological Sciences Research Council (BB/W016753/1 to AB, TARP and RRS) and a Heisenberg fellowship from the German Research Foundation (FR 2973/11-1 to CF).1. Exposure to extreme temperatures can negatively affect animal reproduction, by disrupting the ability of individuals to produce any offspring (fertility), or the number of offspring produced by fertile individuals (fecundity). This has important ecological consequences, because reproduction is the ultimate measure of population fitness: a reduction in reproductive output lowers the population growth rate and increases the extinction risk. Despite this importance, there have been no large‐scale summaries of the evidence for effect of temperature on reproduction. 2. We provide a systematic map of studies testing the relationship between temperature and animal reproduction. We systematically searched for published studies that statistically test for a direct link between temperature and animal reproduction, in terms of fertility, fecundity or indirect measures of reproductive potential (gamete and gonad traits). 3. Overall, we collated a large and rich evidence base, with 1654 papers that met our inclusion criteria, encompassing 1191 species. 4. The map revealed several important research gaps. Insects made up almost half of the dataset, but reptiles and amphibians were uncommon, as were non‐arthropod invertebrates. Fecundity was the most common reproductive trait examined, and relatively few studies measured fertility. It was uncommon for experimental studies to test exposure of different life stages, exposure to short‐term heat or cold shock, exposure to temperature fluctuations, or to independently assess male and female effects. Studies were most often published in journals focusing on entomology and pest control, ecology and evolution, aquaculture and fisheries science, and marine biology. Finally, while individuals were sampled from every continent, there was a strong sampling bias towards mid‐latitudes in the Northern Hemisphere, such that the tropics and polar regions are less well sampled. 5. This map reveals a rich literature of studies testing the relationship between temperature and animal reproduction, but also uncovers substantial missing treatment of taxa, traits, and thermal regimes. This database will provide a valuable resource for future quantitative meta‐analyses, and direct future studies aiming to fill identified gaps.Publisher PDFPeer reviewe

Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma.

Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide association studies (GWAS). This meta-analysis combines 11 GWAS (5 previously unpublished) and a further three stage 2 data sets, totaling 15,990 CMM cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P < 5 × 10(-8)), as did 2 previously reported but unreplicated loci and all 13 established loci. Newly associated SNPs fall within putative melanocyte regulatory elements, and bioinformatic and expression quantitative trait locus (eQTL) data highlight candidate genes in the associated regions, including one involved in telomere biology.[Please see the Supplementary Note for acknowledgments.]This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.337

Cell cycle-independent phospho-regulation of Fkh2 during hyphal growth regulates Candida albicans pathogenesis.

The opportunistic human fungal pathogen, Candida albicans, undergoes morphological and transcriptional adaptation in the switch from commensalism to pathogenicity. Although previous gene-knockout studies have identified many factors involved in this transformation, it remains unclear how these factors are regulated to coordinate the switch. Investigating morphogenetic control by post-translational phosphorylation has generated important regulatory insights into this process, especially focusing on coordinated control by the cyclin-dependent kinase Cdc28. Here we have identified the Fkh2 transcription factor as a regulatory target of both Cdc28 and the cell wall biosynthesis kinase Cbk1, in a role distinct from its conserved function in cell cycle progression. In stationary phase yeast cells 2D gel electrophoresis shows that there is a diverse pool of Fkh2 phospho-isoforms. For a short window on hyphal induction, far before START in the cell cycle, the phosphorylation profile is transformed before reverting to the yeast profile. This transformation does not occur when stationary phase cells are reinoculated into fresh medium supporting yeast growth. Mass spectrometry and mutational analyses identified residues phosphorylated by Cdc28 and Cbk1. Substitution of these residues with non-phosphorylatable alanine altered the yeast phosphorylation profile and abrogated the characteristic transformation to the hyphal profile. Transcript profiling of the phosphorylation site mutant revealed that the hyphal phosphorylation profile is required for the expression of genes involved in pathogenesis, host interaction and biofilm formation. We confirmed that these changes in gene expression resulted in corresponding defects in pathogenic processes. Furthermore, we identified that Fkh2 interacts with the chromatin modifier Pob3 in a phosphorylation-dependent manner, thereby providing a possible mechanism by which the phosphorylation of Fkh2 regulates its specificity. Thus, we have discovered a novel cell cycle-independent phospho-regulatory event that subverts a key component of the cell cycle machinery to a role in the switch from commensalism to pathogenicity