Autophagic Upregulation Is Cytoprotective in Ischemia/Reperfusion-Injured Retina and Retinal Progenitor Cells

The cytoprotective versus cytotoxic role of macroautophagy in ocular ischemia/reperfusion injuries remains controversial and its effects under hyperglycemia are unclear. We investigated the involvement of autophagy in in vitro and in vivo normoglycemic and hyperglycemic models of retinal ischemia/reperfusion injury. Retinal ischemia (2 h) and reperfusion (2 or 22 h) was induced in wild-type and type I diabetic Ins2^Akita/+ mice using a middle cerebral artery occlusion model. R28 retinal precursor cells were subjected to CoCl₂-induced hypoxia with or without autophagic inhibitor NH₄Cl. Autophagic regulation during ischemia/reperfusion was assessed through immunohistochemical detection and Western blotting of microtubule-associated protein 1A/1B-light chain 3 (LC3) and lysosomal associated membrane protein 1 (LAMP1). Effect of autophagic inhibition on cell viability and morphology under hypoxic conditions was also evaluated. Upregulation of autophagic markers in the inner retinae was seen after two hours reperfusion, with tapering of the response following 22 h of reperfusion in vivo. LC3-II turnover assays confirmed an increase in autophagic flux in our hypoxic in vitro model. Pharmacological autophagic inhibition under hypoxic conditions decreased cell survival and induced structural changes not demonstrated with autophagic inhibition alone. Yet no statistically significant different autophagic responses in ischemia/reperfusion injuries were seen between the two glycemic states.     

A 2.7–6.1 GHz CMOS local oscillator based on frequency multiplication by 3/2

Frequency multiplication by 3/2 is proposed as a means to expand the frequency generation capabilities of a single LC VCO. Fractional frequency multiplication is obtained by cascading a broadband injection locked modulo-two divider and a multiply-by-three circuit based on edge combining. The proposed solution is inductorless, thus very compact. It allows the generation of all frequencies from 2.7 to 6.1 GHz with a performance suitable for cellular standards. It shows a phase noise floor below ?150 dBc/Hz and a spurious level below ?35 dBc. The multiplier by 3/2 consumes 5 mA and the VCO draws 10 mA from a 1.2 V supply. The additional power consumption due to the multiplier trades with the small area penalty and the flexibility of this solution, compared to the use of multiple LC VCOs.     

Temperature dependence of neutron-induced soft errors in SRAMs

We irradiated commercial SRAMs with wide-spectrum neutrons at different temperatures. We observed that, depending on the vendor, the soft error rate either increases or slightly decreases with temperature, even in devices belonging to the same technology node. SPICE simulations were used to investigate the temperature dependence of the cell feedback time and restoring current. The shape and magnitude of the particle-induced transient current is discussed as a function of temperature. The variability in the response is attributed to the balance of contrasting factors, such as cell speed reduction and increased diffusion with increasing temperature.     

Self reported risk taking and risk compensation in skiers and snowboarders are associated with sensation seeking

In alpine skiing, a controversial discussion has been taking place regarding the potential influence of wearing a ski helmet on the individual level of risk taking behaviour. The aim of this study was to evaluate whether self reported risk taking behaviour and self reported risk compensation are associated with the personality trait sensation seeking (SS) in alpine skiing and snowboarding. In total, 683 persons (36% males and 64% females) completed an online-survey about attitudes and use of protective gear in winter sports including the German version of the sensation seeking scale form V. A logistic regression analysis including gender, age, nationality, preferred winter sport, self reported skiing ability, mean skiing time per season, use of ski helmets, and SS total score was used to estimated adjusted odds ratios (ORs) and their 95% confidence intervals (95 CI) for self reported risk taking behaviour. Regression analysis revealed that a more risky behaviour increased with male gender (OR: 2.7), with an age < 25 years (OR: 1.6), with skiing (OR: 1.3), higher skill level (OR: 5.7), and a mean skiing time > 28 days per season (OR: 2.2). In addition, SS total score was significantly higher in more risky compared to more cautious people (23.8 vs. 20.3, p < .001). Ski helmet use was not found to be predictive for a more risky behaviour (p > .05). Also, skiers and snowboarders with self reported risk compensation while wearing a ski helmet had higher SS total scores compared to those who did not report risk compensation (23.8 vs. 20.9, p = .001). In addition, self reported risk compensation in helmet wearers increased with an age < 25 years (OR: 2.2), a higher skill level (OR: 2.5) and a mean skiing time > 28 days per season (OR: 2.1). In conclusion, self reported risk taking and self reported risk compensation are associated with higher sensation seeking total scores. The personality trait sensation seeking, not wearing of a ski helmet, appears to be associated with riskier behaviour on the ski slopes.     

Investigation of the Photocatalytic Hydrogen Production of Semiconductor Nanocrystal-Based Hydrogels

Destabilization of a ligand-stabilized semiconductor nanocrystal solution with an oxidizing agent can lead to a macroscopic highly porous self-supporting nanocrystal network entitled hydrogel, with good accessibility to the surface. The previously reported charge carrier delocalization beyond a single nanocrystal building block in such gels can extend the charge carrier mobility and make a photocatalytic reaction more probable. The synthesis of ligand-stabilized nanocrystals with specific physicochemical properties is possible, thanks to the advances in colloid chemistry made in the last decades. Combining the properties of these nanocrystals with the advantages of nanocrystal-based hydrogels will lead to novel materials with optimized photocatalytic properties. This work demonstrates that CdSe quantum dots, CdS nanorods, and CdSe/CdS dot-in-rod-shaped nanorods as nanocrystal-based hydrogels can exhibit a much higher hydrogen production rate compared to their ligand-stabilized nanocrystal solutions. The gel synthesis through controlled destabilization by ligand oxidation preserves the high surface-to-volume ratio, ensures the accessible surface area even in hole-trapping solutions and facilitates photocatalytic hydrogen production without a co-catalyst. Especially with such self-supporting networks of nanocrystals, the problem of colloidal (in)stability in photocatalysis is circumvented. X-ray photoelectron spectroscopy and photoelectrochemical measurements reveal the advantageous properties of the 3D networks for application in photocatalytic hydrogen production.     

Origin and Evolution of the Human Bcl2-Associated Athanogene-1 (BAG-1)

Molecular chaperones, particularly the 70-kDa heat shock proteins (Hsp70s), are key orchestrators of the cellular stress response. To perform their critical functions, Hsp70s require the presence of specific co-chaperones, which include nucleotide exchange factors containing the BCL2-associated athanogene (BAG) domain. BAG-1 is one of these proteins that function in a wide range of cellular processes, including apoptosis, protein refolding, and degradation, as well as tumorigenesis. However, the origin of BAG-1 proteins and their evolution between and within species are mostly uncharacterized. This report investigated the macro- and micro-evolution of BAG-1 using orthologous sequences and single nucleotide polymorphisms (SNPs) to elucidate the evolution and understand how natural variation affects the cellular stress response. We first collected and analyzed several BAG-1 sequences across animals, plants, and fungi; mapped intron positions and phases; reconstructed phylogeny; and analyzed protein characteristics. These data indicated that BAG-1 originated before the animals, plants, and fungi split, yet most extant fungal species have lost BAG-1. Furthermore, although BAG-1’s structure has remained relatively conserved, kingdom-specific conserved differences exist at sites of known function, suggesting functional specialization within each kingdom. We then analyzed SNPs from the 1000 genomes database to determine the evolutionary patterns within humans. These analyses revealed that the SNP density is unequally distributed within the BAG1 gene, and the ratio of non-synonymous/synonymous SNPs is significantly higher than 1 in the BAG domain region, which is an indication of positive selection. To further explore this notion, we performed several biochemical assays and found that only one out of five mutations tested altered the major co-chaperone properties of BAG-1. These data collectively suggest that although the co-chaperone functions of BAG-1 are highly conserved and can probably tolerate several radical mutations, BAG-1 might have acquired specialized and potentially unexplored functions during the evolutionary process.     

Ethische Aspekte des Alter(n)s im Kontext von Medizin und Gesundheitsversorgung: Problemaufriss und Forschungsperspektiven

Definition of the problem

Due to the individual and societal consequences of demographic change, moral questions regarding old age and elderly persons are moving into the focus of public attention and of ethical debates in medicine, nursing and public health. In many of these debates, however, ageing as a process and old age as a phase of life is primarily considered from the angle of the respective practices, questions and problems discussed. What is missing is a perspective that comprises the different practical contexts, makes the underlying conceptions of age(ing) explicit and reflects their meaning for the ethical debate.

Arguments

The working group “Ageing and Ethics” in the Academy for Ethics in Medicine was established to contribute to such a more comprehensive perspective. This paper gives an overview of the central topics, problems and arguments in the contemporary medical, nursing and public health ethics discourses on age(ing) and marks open questions and desiderates.

Conclusions

A more intensive consideration of age(ing) can not only improve the theoretical basis of the pertaining debates in applied ethics but also shed light on some of the anthropological foundations and normative frameworks of ethical reasoning as such.