Anticipatory Planning Reveals Segmentation of Cortical Motor Output During Action Observation

It has been argued that the variation in brain activity that occurs when observing another person reflects a representation of actions that is indivisible, and which plays out in full once the intent of the actor can be discerned. We used transcranial magnetic stimulation to probe the excitability of corticospinal projections to 2 intrinsic hand muscles while motions to reach and grasp an object were observed. A symbolic cue either faithfully indicated the required final orientation of the object and thus the nature of the grasp that was required, or was in conflict with the movement subsequently displayed. When the cue was veridical, modulation of excitability was in accordance with the functional role of the muscles in the action observed. If however the cue had indicated that the alternative grasp would be required, modulation of output to first dorsal interosseus was consistent with the action specified, rather than the action observed-until the terminal phase of the motion sequence during which the object was seen lifted. Modulation of corticospinal output during observation is thus segmented-it progresses initially in accordance with the action anticipated, and if discrepancies are revealed by visual input, coincides thereafter with that of the action seen.

Endothelial progenitor cells in diabetic retinopathy

Diabetic retinopathy (DR) is a leading cause of visual impairment worldwide. Patients with DR may irreversibly lose sight as a result of the development of diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR); retinal blood vessel dysfunction and degeneration plays an essential role in their pathogenesis. Although new treatments have been recently introduced for DME, including intravitreal vascular endothelial growth factor inhibitors (anti-VEGFs) and steroids, a high proportion of patients (~40-50%) do not respond to these therapies. Furthermore, for people with PDR, laser photocoagulation remains a mainstay therapy despite this being an inherently destructive procedure. Endothelial progenitor cells (EPCs) are a low-frequency population of circulating cells known to be recruited to sites of vessel damage and tissue ischemia where they promote vascular healing and re-perfusion. A growing body of evidence suggests that the number and function of EPCs are altered in patients with varying degrees of diabetes duration, metabolic control, and in the presence or absence of DR. Although there are no clear-cut outcomes from these clinical studies, there is mounting evidence that some EPC sub-types may be involved in the pathogenesis of DR and may also serve as biomarkers for disease progression and stratification. Moreover, some EPC sub-types have considerable potential as therapeutic modalities for DME and PDR in the context of cell therapy. This study presents basic clinical concepts of DR and combines this with a general insight on EPCs and their relation to future directions in understanding and treating this important diabetic complication.

ARTD1/PARP1 Negatively Regulates Glycolysis by Inhibiting Hexokinase 1 Independent of NAD(+) Depletion

ARTD1 (PARP1) is a key enzyme involved in DNA repair through the synthesis of poly(ADP-ribose) (PAR) in response to strand breaks, and it plays an important role in cell death following excessive DNA damage. ARTD1-induced cell death is associated with NAD(+) depletion and ATP loss; however, the molecular mechanism of ARTD1-mediated energy collapse remains elusive. Using real-time metabolic measurements, we compared the effects of ARTD1 activation and direct NAD(+) depletion. We found that ARTD1-mediated PAR synthesis, but not direct NAD(+) depletion, resulted in a block to glycolysis and ATP loss. We then established a proteomics-based PAR interactome after DNA damage and identified hexokinase 1 (HK1) as a PAR binding protein. HK1 activity is suppressed following nuclear ARTD1 activation and binding by PAR. These findings help explain how prolonged activation of ARTD1 triggers energy collapse and cell death, revealing insight into the importance of nucleus-to-mitochondria communication via ARTD1 activation.

Women's Nightwork :deregulation as a straight road to equality?

The book considers the question whether the traditional prohibition of nightwork for female manual workers could be defended against EU (then: EEC) discrimination law requirements and against the German constitution itself. While I was working on the PhD, German labour law still prohibited manual workers (but not white collar employees, or nurses, or policewomen) from working nights. Just before the thesis was published, the German constitutional court held that the prohibition indeed violates the Constitution, but that it must not be repealed without providing for specific protection against health risks ensuing from night work. The Court thus mainly confirmed the thesis' results. The thesis first considers the history of the legislation (which was based on an ILO convention), and discusses the social and health risks related to night work. It then comes to the conclusion that gender roles imply that women are at a greater risk when working nights, but that there is no biological justification (except during pregnancy of course). The thesis further develops a recommendation, based on the constitutional welfare states principle and the constitutional protection of health, to not just abolish the prohibition, but to provide uplevel equalisation of working conditions for women and men. This was the first time I also tried to work comparatively (not perfect at all), but I have certainly improved since then. An English summary of the thesis was published in the 3rd issue of the Cardozo Women's Law Journal 1996, which was also my first ever publicatin in English

FRP-to-concrete bond-slip behaviour under dynamic loading

Strengthening reinforced concrete (RC) structures by externally bonded FRP composites has been widely used for static loading and seismic retrofitting since 1990s. More recently many studies on strengthening concrete and masonry structures with externally bonded FRP for improved blast and impact resistance in protective engineering have also been conducted. The bond behaviour between the FRP and concrete plays a critical role in a strengthening system with externally bonded FRP. However, the understanding of how the bond between FRP and concrete performs under high strain rate is severely limited. Due to the dynamic characteristics of blast and impact loading, the bond behaviour between FRP and concrete under such loading is very different from that under static loading. This paper presents a study on the dynamic bond-slip behaviour based on both the numerical analysis and test results. A dynamic bond-slip model is proposed in this paper.