Mouse models of neurodegenerative disease: preclinical imaging and neurovascular component.

Neurodegenerative diseases represent great challenges for basic science and clinical medicine because of their prevalence, pathologies, lack of mechanism-based treatments, and impacts on individuals. Translational research might contribute to the study of neurodegenerative diseases. The mouse has become a key model for studying disease mechanisms that might recapitulate in part some aspects of the corresponding human diseases. Neurode- generative disorders are very complicated and multifacto- rial. This has to be taken in account when testing drugs. Most of the drugs screening in mice are very di cult to be interpretated and often useless. Mouse models could be condiderated a ‘pathway models’, rather than as models for the whole complicated construct that makes a human disease. Non-invasive in vivo imaging in mice has gained increasing interest in preclinical research in the last years thanks to the availability of high-resolution single-photon emission computed tomography (SPECT), positron emission tomography (PET), high eld Magnetic resonance, Optical Imaging scanners and of highly speci c contrast agents. Behavioral test are useful tool to characterize di erent ani- mal models of neurodegenerative pathology. Furthermore, many authors have observed vascular pathological features associated to the di erent neurodegenerative disorders. Aim of this review is to focus on the di erent existing animal models of neurodegenerative disorders, describe behavioral tests and preclinical imaging techniques used for diagnose and describe the vascular pathological features associated to these diseases

Gender-Specific Occupational Segregation, Glass Ceiling Effects, and Earnings in Managerial Positions: Results of a Fixed Effects Model

The study analyses the gender pay gap in private-sector management positions based on the German Socio-Economic Panel Study (SOEP) for the years 2001-2008. It focuses on occupational gender segregation, and on the effects of this inequality on earnings levels and gender wage differentials in management positions. Our paper is, to our knowledge, the first in Germany to use time-constant unobserved heterogeneity and gender-specific promotion probabilities to estimate wages and wage differentials for persons in managerial positions. The results of the fixed-effects model show that working in a more female job, as opposed to a more male job, affects only women's wages negatively. This result remains stable after controlling for human capital endowments and other effects. Mechanisms of the devaluation of jobs not primarily held by men also negatively affect pay in management positions (evaluative discrimination) and are even more severe for women (allocative discrimination). However, the effect is non-linear; the wage penalties for women occur only in integrated (more equally male/female) jobs as opposed to typically male jobs, and not in typically female jobs. The devaluation of occupations that are not primarily held by men becomes even more evident when promotion probabilities are taken into account. An Oaxaca/Blinder decomposition of the wage differential between men and women in management positions shows that the full model explains 65 percent of the gender pay gap. In other words: Thirty-five percent remain unexplained; this portion reflects, for example, time-varying social and cultural conditions, such as discriminatory policies and practices in the labor market

Activation of the Wnt/β-catenin signaling cascade after traumatic nerve injury.

Recent data have shown that preservation of the neuromuscular junction (NMJ) after traumatic nerve injury helps to improve functional recovery with surgical repair via matrix metalloproteinase-3 (MMP3) blockade. As such, we sought to explore additional pathways that may augment this response. Wnt3a has been shown to inhibit acetylcholine receptor (AChR) clustering via β-catenin-dependent signaling in the development of the NMJ. Therefore, we hypothesized that Wnt3a and β-catenin are associated with NMJ destabilization following traumatic denervation. A critical size nerve defect was created by excising a 10-mm segment of the sciatic nerve in mice. Denervated muscles were then harvested at multiple time points for immunofluorescence staining, quantitative real-time PCR, and western blot analysis for Wnt3a and β-catenin levels. Moreover, a novel Wnt/β-catenin transgenic reporter mouse line was utilized to support our hypothesis of Wnt activation after traumatic nerve injury. The expression of Wnt3a mRNA was significantly increased by 2 weeks post-injury and remained upregulated for 2 months. Additionally, β-catenin was activated at 2 months post-injury relative to controls. Correspondingly, immunohistochemical analysis of denervated transgenic mouse line TCF/Lef:H2B-GFP muscles demonstrated that the number of GFP-positive cells was increased at the motor endplate band. These collective data support that post-synaptic AChRs destabilize after denervation by a process that involves the Wnt/β-catenin pathway. As such, this pathway serves as a potential therapeutic target to prevent the motor endplate degeneration that occurs following traumatic nerve injury

Use of radar data for characterizing extreme precipitation at fine scales and short durations

Extreme precipitation is one of the most devastating forms of atmospheric phenomenon, causing severe damage worldwide, and is likely to intensify in strength and occurrence in a warming climate. This contribution gives an overview of the potential and challenges associated with using weather radar data to investigate extreme precipitation. We illustrate this by presenting radar data sets for Germany, the U.S. and the UK that resolve small-scale heavy rainfall events of just a few km ^2 with return periods of 5 years or more. Current challenges such as relatively short radar records and radar-based QPE uncertainty are discussed. An example from a precipitation climatology derived from the German weather radar network with spatial resolution of 1 km reveals the necessity of radars for observing short-term (1–6 h) extreme precipitation. Only 17.3% of hourly heavy precipitation events that occurred in Germany from 2001 to 2018 were captured by the rain gauge station network, while 81.8% of daily events were observed. This is underlined by a similar study using data from the UK radar network for 2014. Only 36.6% (52%) of heavy hourly (daily) rain events detected by the radar network were also captured by precipitation gauging stations. Implications for the monitoring of hydrologic extremes are demonstrated over the U.S. with a continental-scale radar-based reanalysis. Hydrologic extremes are documented over ∼1000 times more locations than stream gauges, including in the majority of ungauged basins. This underlines the importance of high-resolution weather radar observations for resolving small-scale rainfall events, and the necessity of radar-based climatological data sets for understanding the small-scale and high-temporal resolution characteristics of extreme precipitation

JESP symposium: climate change and social policy

Climate change is surely one of the most encompassing and egregious threats in Europe today, so it is appropriate that we consider its implications for social policy in Europe. It is true that climate change is a separate agenda, the preserve of a distinct academic and epistemic community, scholarly discourse, policy community, institutional structures and modes of governance; but the linkages between these two issues – climate change and its policy corollaries, and the ‘traditional’ domain of social policies – seem to us so strong and salient that they should be aired in a social policy journal

Latent regeneration abilities persist following recent evolutionary loss in asexual annelids

Regeneration abilities have been repeatedly lost in many animal phyla. However, because regeneration research has focused almost exclusively on highly regenerative taxa or on comparisons between regenerating and nonregenerating taxa that are deeply diverged, virtually nothing is known about how regeneration loss occurs. Here, we show that, following a recent evolutionary loss of regeneration, regenerative abilities can remain latent and still be elicited. Using comparative regeneration experiments and a molecular phylogeny, we show that ancestral head regeneration abilities have been lost three times among naidine annelids, a group of small aquatic worms that typically reproduce asexually by fission. In all three lineages incapable of head regeneration, worms consistently seal the wound but fail to progress to the first stage of tissue replacement. However, despite this coarse-level convergence in regeneration loss, further investigation of two of these lineages reveals marked differences in how much of the regeneration machinery has been abolished. Most notably, in a species representing one of these two lineages, but not in a representative of the other, amputation within a narrow proliferative region that forms during fission can still elicit regeneration of an essentially normal head. Thus, the presence at the wound site of elements characteristic of actively growing tissues, such as activated stem cells or growth factors, may permit blocks to regeneration to be circumvented, allowing latent regeneration abilities to be manifested