Prevalence of tetrahydrobiopterine (BH4)-responsive alleles among Austrian patients with PAH deficiency: comprehensive results from molecular analysis in 147 patients

Phenylketonuria (PKU, MIM 261600) is an autosomal recessive disorder caused by mutations of the phenylalanine hydroxylase gene (PAH, GenBank U49897.1, RefSeq NM_000277). To date more than 560 variants of the PAH gene have been identified. In Europe there is regional distribution of specific mutations. Due to recent progress in chaperone therapy, the prevalence of BH4-responsive alleles gained therapeutic importance. Here we report the mutational spectrum of PAH deficiency in 147 unrelated Austrian families. Overall mutation detection rate was 98.6%. There was a total of 62 disease-causing mutations, including five novel mutations IVS4 + 6T>A, p.H290Y, IVS8-2A>G, p.A322V and p.I421S. The five most prevalent mutations found in patients were p.R408W, IVS12 + 1G>A, p.R261Q, p.R158Q and IVS2 + 5G>C. Neonatal phenylalanine levels before treatment were available in 114/147 patients. Prediction of BH4-responsiveness in patients with full genotypes was exclusively made according to published data. Among the 133 patients needing dietary treatment, 28.4% are expected to be BH4 "non-responsive", 4.5% are highly likely BH4-responsive, 35.8% are probably BH4-responsive while no interpretation was possible for 31.3%. The mutation data reflect the population history of Austria and provide information on the likely proportion of Austrian PKU patients that may benefit from BH4-therap

3D Bioprinting in Microgravity: Opportunities, Challenges, and Possible Applications in Space

: 3D bioprinting has developed tremendously in the last couple of years and enables the fabrication of simple, as well as complex, tissue models. The international space agencies have recognized the unique opportunities of these technologies for manufacturing cell and tissue models for basic research in space, in particular for investigating the effects of microgravity and cosmic radiation on different types of human tissues. In addition, bioprinting is capable of producing clinically applicable tissue grafts, and its implementation in space therefore can support the autonomous medical treatment options for astronauts in future long term and far-distant space missions. The article discusses opportunities but also challenges of operating different types of bioprinters under space conditions, mainly in microgravity. While some process steps, most of which involving the handling of liquids, are challenging under microgravity, this environment can help overcome problems such as cell sedimentation in low viscous bioinks. Hopefully, this publication will motivate more researchers to engage in the topic, with publicly available bioprinting opportunities becoming available at the International Space Station (ISS) in the imminent future

Focus: Implementing participation - Advancement of social services in analog and digital spaces

Digitale Informations- und Kommunikationstechnologien gewinnen als fester Bestandteil zunehmend Bedeutung in den alltäglichen Lebenswelten einer wachsenden Zahl von Menschen. Ihre Entwicklung und selbstverständliche Nutzung schreiten in einem immer rasanteren Tempo voran; die vielfältigen Anwendungsmöglichkeiten adressieren längst alle Lebensbereiche. Während der Digitalisierung von Kommunikationsprozessen zuweilen demokratisierende Kräfte zugesprochen werden, scheint eine kritische Reflexion möglicher Potentiale und Auswirkungen digitaler Informations- und Kommunikationstechnologien auf Teilhabedynamiken in unterschiedlichen Lebensbereichen dringend erforderlich. Die Autorinnen und Autoren möchten mit dieser SI:SO-Schwerpunktausgabe einen Beitrag zu einer kritischen Reflexion digitaler Innovationen und ihrer Auswirkungen auf die zukünftige Gestaltung sozialer Dienste leisten. Mit der zweisprachigen Ausgabe ist zudem die Hoffnung verbunden, diesen Beitrag auch einem europäischen und weltweiten Publikum zugänglich zu machen.Digital information and communications technologies are becoming an increasingly important part in everyday life of a growing number of people. Their development and natural use are progressing even faster with a wide range of possible applications addressing all areas of life. While the digitization of communication processes is sometimes said to have democratizing forces, critical reflection on the potential and impact of digital information and communication technologies on participation dynamics in different areas of life seems urgently needed. The Authors would like to contribute to a critical reflection on digital innovations and their impact on the future design of social services. The bilingual edition further aims to make this contribution accessible to a European and global audience

3D Bioprinting in Microgravity: Opportunities, Challenges, and Possible Applications in Space

3D bioprinting has developed tremendously in the last couple of years and enables the fabrication of simple, as well as complex, tissue models. The international space agencies have recognized the unique opportunities of these technologies for manufacturing cell and tissue models for basic research in space, in particular for investigating the effects of microgravity and cosmic radiation on different types of human tissues. In addition, bioprinting is capable of producing clinically applicable tissue grafts, and its implementation in space therefore can support the autonomous medical treatment options for astronauts in future long term and far-distant space missions. The article discusses opportunities but also challenges of operating different types of bioprinters under space conditions, mainly in microgravity. While some process steps, most of which involving the handling of liquids, are challenging under microgravity, this environment can help overcome problems such as cell sedimentation in low viscous bioinks. Hopefully, this publication will motivate more researchers to engage in the topic, with publicly available bioprinting opportunities becoming available at the International Space Station (ISS) in the imminent future

Flow-field in the vicinity of high-pressure-drop ball valve

Peer reviewed: YesNRC publication: Ye

General scheme for oxidative quenching of a copper bis-phenanthroline photosensitizer for light-driven hydrogen production

A new, general reaction scheme for photocatalytic hydrogen production is presented based on oxidative quenching of a homoleptic copper(I) bis-1,10-phenanthroline photosensitizer (PS) by 1-methyl-4-phenyl-pyridinium (MPP(+) ) as the electron relay and subsequent regeneration of the so formed copper(II) complex by a sacrificial electron donor. Electron transfer from the relay to various cobalt based water reduction catalysts and subsequent H2 production was shown to close the catalytic cycle. Transient absorption experiments unambiguously confirmed the proposed pathway, both the oxidative quenching and subsequent regeneration of oxidized PS. Photocatalytic test runs further confirmed the role of MPP(+) and up to 10 turnovers were achieved in the relay. The performance limiting factor of the system was shown to be the decomplexation of the copper PS. Quantum yields of the system were 0.03 for H2 production, but 0.6 for MPP(.) formation, clearly indicating that unproductive pathways still prevail

SnIVMetalloporphyrin/CoIII Complex: An All-Abundant-Element System for the Photocatalytic Production of H2 in Aqueous Solution

A new, molecular system for the light-driven production of hydrogen in aqueous solution was developed by combining a water-soluble tin porphyrin ([SnIVCl2TPPC], A) acting as photosensitizer with a cobalt-based proton-reduction catalyst ([CoIIICl(dmgH)2(py)], C). Under visible light illumination and with triethanolamine (TEOA) as electron source, the system evolves H2 for hours and is clearly catalytic in both dye and catalyst. A detailed analysis of the relevant redox potentials in combination with time-resolved spectroscopy resulted in the development of a Z-scheme type model for the flow of electrons in this system. Key intermediates of the proposed mechanism for the pathway leading to H2 are the porphyrin dye’s highly oxidizing singlet excited state 1A* (E ∼ +1.3 V vs NHE), its strongly reducing isobacteriochlorin analogue (E ∼ +0.95 V), and the CoI form of C (E ∼ −0.8 V), acting as catalyst for H2 formation. Among other results, the suggested reaction sequence is supported by the detection of a shortened excited-state lifetime for singlet 1A* (τ ∼ 1.75 ns) in the presence of TEOA and the ultraviolet–visible detection of the SnIV isobacteriochlorin intermediate at λ = 610 nm. Thus, a molecular, conceptually biomimetic, and precious-metal-free reaction chain was found which photocatalytically generates H2 in a 100% aqueous system from an electron donor with a high oxidation potential (E(TEOA) ∼ +1.1 V). On the other hand, at identical conditions, this photoreaction chain yields H2 markedly slower than a system using the photosensitizer [ReI(CO)3(bpy) (py)]+, probably due to the much longer excited-state lifetime (τ ∼ 120 ns) of the rhenium dye and better electron-transfer rates caused by its simple single-electron photoreduction chemistry