Recycling process development with integrated life cycle assessment - a case study on oxygen transport membrane material

The transformation towards a circular economy based on sustainable technologies requires future-oriented materials development, which considers materials recycling with a minimum environmental impact (EI). This demands a holistic approach towards materials design, including a combined assessment of functional and environmental performance. Scientific methods for environmental assessment, e.g., life cycle assessment (LCA), are well established but rarely integrated into the chemical process development at early stages. Consequently, sustainability claims often lack scientific verification. Here, we test the approach of integrating a screening LCA into the development of a chemical (recycling) process. As a relevant use case, we selected the recently developed oxygen transport membrane (OTM) material (La0.9Ca0.1)2Ni0.75Cu0.25O4±δ (LCNC). An initial LCA identified the consumption of primary metal nitrates as a major contributor to the EI of the primary synthesis. To address this issue, a Pechini-based chemical recycling process for LCNC was developed, which involves microwave-heated dissolution and subsequent re-gelation. Experimental results demonstrate the synthesis of recycled LCNC powder with primary-like properties, similar reaction behaviour, and >96% yield. Based on the LCA results, the EI of recycling is reduced by up to 76% compared to the primary synthesis in 12 of 14 impact categories. Measures for the simultaneous improvement of the process functionality and environmental performance were identified. The approach of integrating LCA in chemical process development is discussed critically based on the given use case. The results strongly encourage the integration of LCA as a standard method into the future development of sustainable chemical processes

Deep Sequencing of MYC DNA-Binding Sites in Burkitt Lymphoma

BACKGROUND: MYC is a key transcription factor involved in central cellular processes such as regulation of the cell cycle, histone acetylation and ribosomal biogenesis. It is overexpressed in the majority of human tumors including aggressive B-cell lymphoma. Especially Burkitt lymphoma (BL) is a highlight example for MYC overexpression due to a chromosomal translocation involving the c-MYC gene. However, no genome-wide analysis of MYC-binding sites by chromatin immunoprecipitation (ChIP) followed by next generation sequencing (ChIP-Seq) has been conducted in BL so far. METHODOLOGY/PRINCIPAL FINDINGS: ChIP-Seq was performed on 5 BL cell lines with a MYC-specific antibody giving rise to 7,054 MYC-binding sites after bioinformatics analysis of a total of approx. 19 million sequence reads. In line with previous findings, binding sites accumulate in gene sets known to be involved in the cell cycle, ribosomal biogenesis, histone acetyltransferase and methyltransferase complexes demonstrating a regulatory role of MYC in these processes. Unexpectedly, MYC-binding sites also accumulate in many B-cell relevant genes. To assess the functional consequences of MYC binding, the ChIP-Seq data were supplemented with siRNA- mediated knock-downs of MYC in BL cell lines followed by gene expression profiling. Interestingly, amongst others, genes involved in the B-cell function were up-regulated in response to MYC silencing. CONCLUSION/SIGNIFICANCE: The 7,054 MYC-binding sites identified by our ChIP-Seq approach greatly extend the knowledge regarding MYC binding in BL and shed further light on the enormous complexity of the MYC regulatory network. Especially our observations that (i) many B-cell relevant genes are targeted by MYC and (ii) that MYC down-regulation leads to an up-regulation of B-cell genes highlight an interesting aspect of BL biology

Movement from the double object construction is not fully symmetrical

A movement asymmetry arises in some languages that are otherwise symmetrical for both A- and A-bar movement in the double object construction (DOC), including Norwegian, North-West British English, and a range of Bantu languages including Zulu and Lubukusu: a Theme object can be A-bar-moved out of a Recipient (Goal) passive, but not vice versa. Our explanation of this asymmetry is based on phase theory, more specifically a stricter version of the Phase Interpretability Condition proposed by Chomsky (2001). The effect is that, in a Theme passive, a Recipient object destined for the C-domain gets trapped within the lower V-related phase by movement of the Theme. The same effect is observed in Italian, a language in which only Theme passives are possible. Moreover, a similar effect is also found in some Bantu languages in connection with object marking/agreement: object agreement with the Theme in a Recipient passive is possible, but not vice versa. We show that this, too, can be understood within the theory that we articulate

Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium

Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest P value 3.87 × 10 -12 for SNP rs634990 in Caucasians, and 9.65 × 10 -4 for rs8032019 in Asians. The overall meta-analysis provided P value 9.20 × 10 -23 for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95 % CI 1.64, 2.16, P < 0.001) for homozygous carriers of the risk allele at the top SNP rs634990, and OR 1.33 (95 % CI 1.19, 1.49, P < 0.001) for heterozygous carriers. SNPs at locus 15q25 did not replicate significantly (P value 5.81 × 10 -2 for top SNP rs939661). We conclude that common variants at chromosome 15q14 influence susceptibility for myopia in Caucasian and Asian populations world-wide. © The Author(s) 2012

Genome-wide association and functional follow-up reveals new loci for kidney function

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

Case report: subacute tetraplegia in an immunocompromised patient

Background: Clinical reasoning in Neurology is based on general associations which help to deduce the site of the lesion. However, even “golden principles” may occasionally be deceptive. Here, we describe the case of subacute flaccid tetraparesis due to motor cortical lesions. To our knowledge, this is the first report to include an impressive illustration of nearly symmetric motor cortical involvement of encephalitis on brain MRI. Case presentation: A 51 year old immunocompromized man developed a high-grade pure motor flaccid tetraparesis over few days. Based on clinical presentation, critical illness polyneuromyopathy was suspected. However, brain MRI revealed symmetrical hyperintensities strictly limited to the subcortical precentral gyrus. An encephalitis, possibly due to CMV infection, turned out to be the most likely cause. Conclusion: While recognition of basic clinical patterns is indispensable in neurological reasoning, awareness of central conditions mimicking peripheral nervous disease may be crucial to detect unsuspected, potentially treatable conditions

All that seems green might be a smokescreen – a case study on microwave-integrated process development of oxygen transport membrane material

To pursue genuine sustainability in materials development, it is essential to incorporate environmental impact assessment right from the outset of the development process. Our case study involving an oxygen transport membrane material illustrates the significance of this coupling. It reveals that, despite bearing products of equivalent functionality, incorporating a commonly perceived green technology may not necessarily result in the expected environmental benefits

Kombinationswirkungen umweltrelevanter Metallverbindungen in Lungenzellen

Zusammenfassung Gesamtziel des Projektes ist die Abklärung der Genotoxizität von löslichen und partikulären, umweltrelevanten Metallverbindungen in menschlichen Lungenzellen als Zielzellen der metallinduzierten Kanzerogenese sowie Kombinationswirkungen mit Benzo[a]pyren als wichtigem Umweltmutagen. Bisher konnte gezeigt werden, dass sowohl lösliches NiCl2 als auch partikuläres schwarzes NiO im nicht-zytotoxischen Bereich in A549 Zellen lediglich eine geringe Anzahl an oxidativen DNA-Schäden induzieren, wohingegen sie die Reparatur von BPDE-induzierten DNA-Addukten in diesem Bereich erheblich hemmen. Die intrazelluläre Verteilung von Nickel, die oftmals für die Unterschiede in der Kanzerogenität von löslichen und partikulären Nickelverbindungen verantwortlich gemacht wird, wurde mit Hilfe der AAS untersucht. Erste Ergebnisse zeigen, dass Nickel entgegen anders lautenden Vermutungen in der Literatur auch nach Inkubation mit löslichen Nickelverbindungen in den Zellkern gelangt, was für die Risikobewertung von großer Bedeutung ist. Zur Zeit untersuchen wir die Induktion von oxidativen DNA Schäden durch lösliche und partikuläre Cadmiumverbindungen und Kombinationswirkungen der entsprechenden Cadmiumverbindungen mit Benzo[a]pyren. Zusätzlich wurde auch die Induktion oxidativer DNA-Schäden durch Arsenit und seine zwei methylierten Metabolite MMA(V) und DMA(V) getestet. Unsere Experimente weisen die Entstehung oxidativer DNA-Basenschäden durch alle drei Verbindungen nach; dies deutet darauf hin, dass es sich bei der Methylierung nicht wie bislang angenommen um eine generelle Detoxifizierung handelt. Summary This project aims to investigate the genotoxicity of soluble and particulate, environmentally relevant metal compounds in human lung cells as primary targets of metal-induced carcinogenicity as well as indirect genotoxic effects in combination with benzo[a]pyrene as an important environmental mutagen. Within this project, we could demonstrate that in A549 cells both soluble NiCl2 and particulate black NiO induce only little oxidative DNA damage in a non-cytotoxic range, whereas they show a pronounced repair inhibition of BPDE-DNA adducts. The intracellular distribution of nickel(II), frequently suggested to be responsible for differences in carcinogenicity of soluble and particulate nickel compounds, has been determined after incubation with different nickel compounds by AAS. First results show that in contrast to the current opinion in literature also soluble nickel(II) reaches the nucleus in significant amounts, a finding of major importance for risk assessment. Currently we investigate the induction of oxidative DNA damage by soluble and particulate cadmium compounds and the combined effects with benzo[a]pyrene. Additionally the induction of oxidative DNA damage by arsenite and its two methylated metabolites MMA(V) and DMA(V) has been examined. Our experiments demonstrate the formation of oxidative DNA modifications by all three compounds, indicating that methylation does not merely resemble detoxification of arsenic compounds