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

Parsing Heterogeneity in the Brain Connectivity of Depressed and Healthy Adults During Positive Mood

There is well-known heterogeneity in affective mechanisms in depression that may extend to positive affect. We used data-driven parsing of neural connectivity to reveal subgroups present across depressed and healthy individuals during positive processing, informing targets for mechanistic intervention

Development and Preliminary Technical Adequacy of Schoolwide Integrated Framework for Transformation Fidelity of Implementation Tool

U.S. public education systems are required to provide free appropriate public education to students with disabilities in least restrictive environments that are appropriate to meet their individual needs. The practice of educating students with disabilities in neighborhood schools in age-appropriate general education classrooms and other school settings to meet this requirement has come to be known as “inclusive education.” The longstanding interest in keeping students with disabilities in the same classrooms with their neighbors and peers has created a need for reform to establish equity in America’s schools. Schoolwide Integrated Framework for Transformation (SWIFT) is a whole-system school reform model provided through a national technical assistance center that addresses core features of inclusive education support for elementary and middle schools, particularly those that are chronically low performing and those serving students with the most extensive needs. We describe the development and preliminary technical adequacy of Schoolwide Integrated Framework for Transformation Fidelity of Implementation Tool (SWIFT-FIT) as a means to document the extent to which schools are implementing inclusive education. Findings provide preliminary support for trained assessors using SWIFT-FIT as a valid and reliable instrument to produce evidence that describes the extent to which schools install, implement, and sustain these evidence-based practices. Researchers and other school personnel can use these data to evaluate the impact of implementation on progress as well as important student and other outcomes

A primordial origin for the atmospheric methane of Saturn's moon Titan

The origin of Titan's atmospheric methane is a key issue for understanding the origin of the Saturnian satellite system. It has been proposed that serpentinization reactions in Titan's interior could lead to the formation of the observed methane. Meanwhile, alternative scenarios suggest that methane was incorporated in Titan's planetesimals before its formation. Here, we point out that serpentinization reactions in Titan's interior are not able to reproduce the deuterium over hydrogen (D/H) ratio observed at present in methane in its atmosphere, and would require a maximum D/H ratio in Titan's water ice 30% lower than the value likely acquired by the satellite during its formation, based on Cassini observations at Enceladus. Alternatively, production of methane in Titan's interior via radiolytic reactions with water can be envisaged but the associated production rates remain uncertain. On the other hand, a mechanism that easily explains the presence of large amounts of methane trapped in Titan in a way consistent with its measured atmospheric D/H ratio is its direct capture in the satellite's planetesimals at the time of their formation in the solar nebula. In this case, the mass of methane trapped in Titan's interior can be up to 1,300 times the current mass of atmospheric methane.Comment: Accepted for publication in Icaru

The Ursinus Weekly, January 10, 1949

Ursinus represented at N.S.A. conference • Clash Dance to feature coming weekend events • New openings made by CCC for jobs in U.S. government • Placement service, reprimands, on list of council\u27s duties • President\u27s speech, Secretary Marshall top news of week • Beardwood\u27s events increase with age • Sensation scored by seniors with Club 49 • Student uncovers recipe for national economic prosperity • Dr. Helen Garrett aids Navy plans at U. of Columbia • What has been your most valuable course? • Open discussion of race equality scheduled by Y • Faculty members attain local honors; Dr. McClure given citizenship award • U.S Medical Corps formed for women • Creager starts chaplain\u27s duties • WSGA holding annual contest to choose May pageant script • Flowers and weeds top Kromka\u27s work • Regional assembly marks anniversary of NSA\u27s 2nd year • Conference delegates reach no conclusion • Future graduates given final notices • French lawyer to speak here tonight • Court lassies open season with Albright on Saturday • Natators commence practice with host of new candidates • Bears break even in league contests • Garnet ties Cadets for division honors • PMC edges Jay-Vees in 35-34 thriller; Cubs bow to Fords in overtime, 47-46 • Jaffe and Reice spark Seeders\u27 five in 47-45 triumph over Main Liners • Cadets open league with 72-50 victory in mid-week gamehttps://digitalcommons.ursinus.edu/weekly/1605/thumbnail.jp

The fundamental connections between the Solar System and exoplanetary science

Over the past several decades, thousands of planets have been discovered outside our Solar System. These planets exhibit enormous diversity, and their large numbers provide a statistical opportunity to place our Solar System within the broader context of planetary structure, atmospheres, architectures, formation, and evolution. Meanwhile, the field of exoplanetary science is rapidly forging onward toward a goal of atmospheric characterization, inferring surface conditions and interiors, and assessing the potential for habitability. However, the interpretation of exoplanet data requires the development and validation of exoplanet models that depend on in situ data that, in the foreseeable future, are only obtainable from our Solar System. Thus, planetary and exoplanetary science would both greatly benefit from a symbiotic relationship with a two way flow of information. Here, we describe the critical lessons and outstanding questions from planetary science, the study of which are essential for addressing fundamental aspects for a variety of exoplanetary topics. We outline these lessons and questions for the major categories of Solar System bodies, including the terrestrial planets, the giant planets, moons, and minor bodies. We provide a discussion of how many of these planetary science issues may be translated into exoplanet observables that will yield critical insight into current and future exoplanet discoveries

Signaling from β1- and β2-adrenergic receptors is defined by differential interactions with PDE4

β1- and β2-adrenergic receptors (βARs) are highly homologous, yet they play clearly distinct roles in cardiac physiology and pathology. Myocyte contraction, for instance, is readily stimulated by β1AR but not β2AR signaling, and chronic stimulation of the two receptors has opposing effects on myocyte apoptosis and cell survival. Differences in the assembly of macromolecular signaling complexes may explain the distinct biological outcomes. Here, we demonstrate that β1AR forms a signaling complex with a cAMP-specific phosphodiesterase (PDE) in a manner inherently different from a β2AR/β-arrestin/PDE complex reported previously. The β1AR binds a PDE variant, PDE4D8, in a direct manner, and occupancy of the receptor by an agonist causes dissociation of this complex. Conversely, agonist binding to the β2AR is a prerequisite for the recruitment of a complex consisting of β-arrestin and the PDE4D variant, PDE4D5, to the receptor. We propose that the distinct modes of interaction with PDEs result in divergent cAMP signals in the vicinity of the two receptors, thus, providing an additional layer of complexity to enforce the specificity of β1- and β2-adrenoceptor signaling

Interpreting response time effects in functional imaging studies

It has been suggested that differential neural activity in imaging studies is most informative if it is independent of response time (RT) differences. However, others view RT as a behavioural index of key cognitive processes, which is likely linked to underlying neural activity. Here, we reconcile these views using the effort and engagement framework developed by Taylor, Rastle, and Davis (2013) and data from the domain of reading aloud. We propose that differences in neural engagement should be independent of RT, whereas, differences in neural effort should co-vary with RT. We illustrate these different mechanisms using data from an fMRI study of neural activity during reading aloud of regular words, irregular words, and pseudowords. In line with our proposals, activation revealed by contrasts designed to tap differences in neural engagement (e.g., words are meaningful and therefore engage semantic representations more than pseudowords) survived correction for RT, whereas activation for contrasts designed to tap differences in neural effort (e.g., it is more difficult to generate the pronunciation of pseudowords than words) correlated with RT. However, even for contrasts designed to tap neural effort, activity remained after factoring out the RT-BOLD response correlation. This may reveal unpredicted differences in neural engagement (e.g., learning phonological forms for pseudowords. >. words) that could further the development of cognitive models of reading aloud. Our framework provides a theoretically well-grounded and easily implemented method for analysing and interpreting RT effects in neuroimaging studies of cognitive processes

Chlamydia trachomatis Incidence and Re-Infection among Young Women – Behavioural and Microbiological Characteristics

This study aimed to estimate rates of chlamydia incidence and re-infection and to investigate the dynamics of chlamydia organism load in prevalent, incident and re-infections among young Australian women.1,116 women aged 16 to 25 years were recruited from primary care clinics in Australia. Vaginal swabs were collected at 3 to 6 month intervals for chlamydia testing. Chlamydia organism load was measured by quantitative PCR.There were 47 incident cases of chlamydia diagnosed and 1,056.34 person years of follow up with a rate of 4.4 per 100 person years (95% CI: 3.3, 5.9). Incident infection was associated with being aged 16 to 20 years [RR = 3.7 (95%CI: 1.9, 7.1)], being employed [RR = 2.4 (95%CI: 1.1, 4.9)] and having two or more new sex partners [RR = 5.5 (95%CI: 2.6, 11.7)]. Recent antibiotic use was associated with a reduced incidence [RR:0.1 (95%CI: 0.0, 0.5)]. There were 14 re-infections with a rate of 22.3 per 100 person years (95%CI: 13.2, 37.6). The median time to re-infection was 4.6 months. Organism load was higher for prevalent than incident infections (p<0.01) and for prevalent than re-infections (p<0.01).Chlamydia is common among young women and a high proportion of women are re-infected within a short period of time, highlighting the need for effective partner treatment and repeat testing. The difference in organism load between prevalent and incident infections suggests prevalent infection may be more important for ongoing transmission of chlamydia