Generation of mouse oocytes defective in cAMP synthesis and degradation: Endogenous cyclic AMP is essential for meiotic arrest

AbstractAlthough it is established that cAMP accumulation plays a pivotal role in preventing meiotic resumption in mammalian oocytes, the mechanisms controlling cAMP levels in the female gamete have remained elusive. Both production of cAMP via GPCRs/Gs/adenylyl cyclases endogenous to the oocyte as well as diffusion from the somatic compartment through gap junctions have been implicated in maintaining cAMP at levels that preclude maturation. Here we have used a genetic approach to investigate the different biochemical pathways contributing to cAMP accumulation and maturation in mouse oocytes. Because cAMP hydrolysis is greatly decreased and cAMP accumulates above a threshold, oocytes deficient in PDE3A do not resume meiosis in vitro or in vivo, resulting in complete female infertility. In vitro, inactivation of Gs or downregulation of the GPCR GPR3 causes meiotic resumption in the Pde3a null oocytes. Crossing of Pde3a−/− mice with Gpr3−/− mice causes partial recovery of female fertility. Unlike the complete meiotic block of the Pde3a null mice, oocyte maturation is restored in the double knockout, although it occurs prematurely as described for the Gpr3−/− mouse. The increase in cAMP that follows PDE3A ablation is not detected in double mutant oocytes, confirming that GPR3 functions upstream of PDE3A in the regulation of oocyte cAMP. Metabolic coupling between oocytes and granulosa cells was not affected in follicles from the single or double mutant mice, suggesting that diffusion of cAMP is not prevented. Finally, simultaneous ablation of GPR12, an additional receptor expressed in the oocyte, does not modify the Gpr3−/− phenotype. Taken together, these findings demonstrate that Gpr3 is epistatic to Pde3a and that fertility as well as meiotic arrest in the PDE3A-deficient oocyte is dependent on the activity of GPR3. These findings also suggest that cAMP diffusion through gap junctions or the activity of additional receptors is not sufficient by itself to maintain the meiotic arrest in the mouse oocyte

Inefficiently Automated Law Enforcement

Article published in the Michigan State Law Review

Checklist for One Health Epidemiological Reporting of Evidence (COHERE).

One Health is defined as the intersection and integration of knowledge regarding humans, animals, and the environment, yet as the One Health scientific literature expands, there is considerable heterogeneity of approach and quality of reporting in One Health studies. In addition, many researchers who publish such studies do not include or integrate data from all three domains of human, animal, and environmental health. This points to a critical need to unify guidelines for One Health studies. This report details the Checklist for One Health Epidemiological Reporting of Evidence (COHERE) to guide the design and publication format of future One Health studies. COHERE was developed by a core writing team and international expert review group that represents multiple disciplines, including human medicine, veterinary medicine, public health, allied professionals, clinical laboratory science, epidemiology, the social sciences, ecohealth and environmental health. The twin aims of the COHERE standards are to 1) improve the quality of reporting of observational or interventional epidemiological studies that collect and integrate data from humans, animals and/or vectors, and their environments; and 2) promote the concept that One Health studies should integrate knowledge from these three domains. The 19 standards in the COHERE checklist address descriptions of human populations, animal populations, environmental assessment, spatial and temporal relationships of data from the three domains, integration of analyses and interpretation, and inclusion of expertise in the research team from disciplines related to human health, animal health, and environmental health

Beyond sunglasses and spray paint: A taxonomy of surveillance countermeasures

Surveillance and privacy are seeming locked in a continual game of one-upmanship. In the security context, adversarial relationships exist where an attacker exploits a vulnerability and the defender responds with countermeasures to prevent future attack or exploitation. From there, the cycle continues, with new vulnerabilities and better exploits, against improved countermeasures. In the privacy context, many have feared the government as a highly empowered threat actor who would invasively and ubiquitously violate privacy, perhaps best personified by DARPA\u27s Total Information Awareness Initiative or Orwell\u27s 1984. However, commercial companies today offer enticing free products and services in return for user information, examples include search social networking, email, and collaborative word processing, among myriad other offerings, leading to instrumentation, data collection, and retention on an unprecedented scale. End users, small business, and local governments themselves are often complicit by supporting, enabling, and conducting such activities. Whether a dystopia exists in our future remains to be seen, although we argue panopticon-like environments exist in today\u27s authoritarian regimes and increasingly surveillance is becoming embedded in the fabric of Western society to thwart terrorism, increase business efficiency, monitor physical fitness, track driving behavior, provide free web search, and many other compelling incentives

Methodological and Practical Considerations in Rapid Qualitative Research: Lessons Learned From a Team-Based Global Study During COVID-19 Pandemic

Rapid qualitative research (RQR) studies are increasingly employed to inform decision-making in public health emergencies. Despite this trend, there remains a lack of clarity around what these studies actually involve in terms of methodological processes and practical considerations or challenges. Our team conducted a global RQR study during the COVID-19 pandemic. In this article, we provide a detailed account of our methodological processes and decisions taken related to ethics, study design, and analysis. We describe how we navigated limitations on time and resources. We draw attention to several elements that operated as facilitators to the rapid launch and completion of this study. Rendering methodological considerations and rationales for specific RQR studies explicit and available for consideration by others can contribute to the validity of RQR, support further discussion and development of RQR methods, and make findings for particular studies more credible

Deconstructing the Relationship Between Privacy and Security [Viewpoint]

From a government or law-enforcement perspective, one common model of privacy and security postulates that security and privacy are opposite ends of a single continuum. While this model has appealing properties, it is overly simplistic. The relationship between privacy and security is not a binary operation in which one can be traded for the other until a balance is found. One fallacy common in privacy and security discourse is that trade-offs are effective or even necessary. Consider the remarks of New York Police Department Commissioner Ray Kelly shortly after the Boston Marathon bombing, “I\u27m a major proponent of cameras. I think the privacy issue has really been taken off the table” [1]. Poorly-designed security measures can consume significant resources without achieving either security or privacy; others can increase security at the expense of privacy. However, with careful consideration, there are solutions that benefit privacy and security