Loss of Magel2, a Candidate Gene for Features of Prader-Willi Syndrome, Impairs Reproductive Function in Mice

Background: MAGEL2 is one of several genes typically inactivated in the developmental obesity disorder Prader-Willi syndrome (PWS). The physiological consequences of loss of MAGEL2, but without the concurrent loss of other PWS genes, are not well understood. Gene-targeted mutation of Magel2 in mice disrupts circadian rhythm and metabolism causing reduced total activity, reduced weight gain before weaning, and increased adiposity after weaning. Principal Findings: We now show that loss of Magel2 in mice causes reduced fertility in both males and females through extended breeding intervals and early reproductive decline and termination. Female Magel2-null mice display extended and irregular estrous cycles, while males show decreased testosterone levels, and reduced olfactory preference for female odors. Conclusions: Our results suggest that loss of MAGEL2 contributes to the reproductive deficits seen in people with PWS, and further highlights the role of normal circadian rhythm in the maintenance of fertility

Coagulation and coagulation signalling in fibrosis

AbstractFollowing tissue injury, a complex and coordinated wound healing response comprising coagulation, inflammation, fibroproliferation and tissue remodelling has evolved to nullify the impact of the original insult and reinstate the normal physiological function of the affected organ. Tissue fibrosis is thought to result from a dysregulated wound healing response as a result of continual local injury or impaired control mechanisms. Although the initial insult is highly variable for different organs, in most cases, uncontrolled or sustained activation of mesenchymal cells into highly synthetic myofibroblasts leads to the excessive deposition of extracellular matrix proteins and eventually loss of tissue function. Coagulation was originally thought to be an acute and transient response to tissue injury, responsible primarily for promoting haemostasis by initiating the formation of fibrin plugs to enmesh activated platelets within the walls of damaged blood vessels. However, the last 20years has seen a major re-evaluation of the role of the coagulation cascade following tissue injury and there is now mounting evidence that coagulation plays a critical role in orchestrating subsequent inflammatory and fibroproliferative responses during normal wound healing, as well as in a range of pathological contexts across all major organ systems. This review summarises our current understanding of the role of coagulation and coagulation initiated signalling in the response to tissue injury, as well as the contribution of uncontrolled coagulation to fibrosis of the lung, liver, kidney and heart. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease

Compton Scattering in Ultra-Strong Magnetic Fields: Numerical and Analytical Behavior in the Relativistic Regime

This paper explores the effects of strong magnetic fields on the Compton scattering of relativistic electrons. Recent studies of upscattering and energy loss by relativistic electrons that have used the non-relativistic, magnetic Thomson cross section for resonant scattering or the Klein-Nishina cross section for non-resonant scattering do not account for the relativistic quantum effects of strong fields ($> 4 \times 10^{12}$ G). We have derived a simplified expression for the exact QED scattering cross section for the broadly-applicable case where relativistic electrons move along the magnetic field. To facilitate applications to astrophysical models, we have also developed compact approximate expressions for both the differential and total polarization-dependent cross sections, with the latter representing well the exact total QED cross section even at the high fields believed to be present in environments near the stellar surfaces of Soft Gamma-Ray Repeaters and Anomalous X-Ray Pulsars. We find that strong magnetic fields significantly lower the Compton scattering cross section below and at the resonance, when the incident photon energy exceeds $m_ec^2$ in the electron rest frame. The cross section is strongly dependent on the polarization of the final scattered photon. Below the cyclotron fundamental, mostly photons of perpendicular polarization are produced in scatterings, a situation that also arises above this resonance for sub-critical fields. However, an interesting discovery is that for super-critical fields, a preponderance of photons of parallel polarization results from scatterings above the cyclotron fundamental. This characteristic is both a relativistic and magnetic effect not present in the Thomson or Klein-Nishina limits.Comment: AASTeX format, 31 pages included 7 embedded figures, accepted for publication in The Astrophysical Journa

Do Situational and Personality Factors Interact to Produce Boredom?

Boredom can be caused by personality characteristics such as the tendency to become frequently bored. Situational factors such as being in a boring situation can also cause boredom. However, situational and personality factors do not work together in producing boredom. Lastly, some individuals experience boredom more often because of an aspect of their personality, regardless of the environment they are in.Knowledge Mobilization at York - York University’s Knowledge Mobilization Unit provides services for faculty, graduate students, community and government seeking to maximize the impact of academic research and expertise on public policy, social programming, and professional practice. This summary has been supported by the Office of the Vice-President Research and Innovation at York and project funding from SSHRC and CIHR. [email protected] www.researchimpact.c

UNC-98 links an integrin-associated complex to thick filaments in Caenorhabditis elegans muscle

Focal adhesions are multiprotein assemblages that link cells to the extracellular matrix. The transmembrane protein, integrin, is a key component of these structures. In vertebrate muscle, focal adhesion–like structures called costameres attach myofibrils at the periphery of muscle cells to the cell membrane. In Caenorhabditis elegans muscle, all the myofibrils are attached to the cell membrane at both dense bodies (Z-disks) and M-lines. Clustered at the base of dense bodies and M-lines, and associated with the cytoplasmic tail of β-integrin, is a complex of many proteins, including UNC-97 (vertebrate PINCH). Previously, we showed that UNC-97 interacts with UNC-98, a 37-kD protein, containing four C2H2 Zn fingers, that localizes to M-lines. We report that UNC-98 also interacts with the C-terminal portion of a myosin heavy chain. Multiple lines of evidence support a model in which UNC-98 links integrin-associated proteins to myosin in thick filaments at M-lines

Compton Scattering in Ultra-Strong Magnetic Fields: Numerical and Analytical Behavior in the Relativistic Regime

This paper explores the effects of strong magnetic fields on the Compton scattering of relativistic electrons. Recent studies of upscattering and energy loss by relativistic electrons that have used the non-relativistic, magnetic Thomson cross section for resonant scattering or the Klein-Nishina cross section for non-resonant scattering do not account for the relativistic quantum effects of strong fields ($> 4 \times 10^{12}$ G). We have derived a simplified expression for the exact QED scattering cross section for the broadly-applicable case where relativistic electrons move along the magnetic field. To facilitate applications to astrophysical models, we have also developed compact approximate expressions for both the differential and total polarization-dependent cross sections, with the latter representing well the exact total QED cross section even at the high fields believed to be present in environments near the stellar surfaces of Soft Gamma-Ray Repeaters and Anomalous X-Ray Pulsars. We find that strong magnetic fields significantly lower the Compton scattering cross section below and at the resonance, when the incident photon energy exceeds $m_ec^2$ in the electron rest frame. The cross section is strongly dependent on the polarization of the final scattered photon. Below the cyclotron fundamental, mostly photons of perpendicular polarization are produced in scatterings, a situation that also arises above this resonance for sub-critical fields. However, an interesting discovery is that for super-critical fields, a preponderance of photons of parallel polarization results from scatterings above the cyclotron fundamental. This characteristic is both a relativistic and magnetic effect not present in the Thomson or Klein-Nishina limits.Comment: AASTeX format, 31 pages included 7 embedded figures, accepted for publication in The Astrophysical Journa

The Covid Sex Lives Project: Health Messaging, Hooking Up And Dating Among Men Who Have Sex With Men During The UK COVID-19 Pandemic

In the context of the pandemic, government and public health measures to mitigate the spread of coronavirus have been translated into media messaging by organisations that target the health of different groups. Engaging experiences of the minority group, men who have sex with men (MSM), we provide evidence on the approaches and responses to these messages in relation to using digital platforms to connect for sexual purposes. Dating and hookup applications, or apps, are a key area where sex and romance has been negotiated over the past two decades, a trend which continued during the pandemic. MSM are an ideal group to look at the challenges posed here as they have been early adopters of these technologies for a variety of purposes, including the obvious ones related to dating and hooking up as well as for increasing more general sociality and reducing loneliness. Due to this culture of engagement with digital media by MSM, and what is known about their sexual cultures, digital platforms have been engaged by health educators in an attempt to improve the sexual health and wellbeing of this group. The question in the context of a pandemic therefore becomes: how are these sexual cultures affected, and how might health messaging be engaged with, or not