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Background Type 2 diabetes and obesity may be inversely associated with amyotrophic lateral sclerosis (ALS), but the evidence is controversial. Methods Using Danish, nationwide registries (1980-2016), we identified patients with a diagnosis of type 2 diabetes (N = 295,653) and patients with a diagnosis of obesity (N = 312,108). Patients were matched (1:3) to persons from the general population on birth year and sex. We computed incidence rates and Cox regression derived hazard ratios (HRs) of a diagnosis of ALS. In multivariable analyses, HRs were controlled for sex, birth year, calendar year, and comorbidities. Results We observed 168 incident cases of ALS (0.7 [95% confidence interval (CI): 0.6–0.8] per 10,000 person-years) among patients with type 2 diabetes and 859 incident cases of ALS (0.9 [95% CI: 0.9–1.0] per 10,000 person-years) among matched comparators. The adjusted HR was 0.87 (95% CI: 0.72–1.04). The association was present among men (adjusted HR: 0.78 [95% CI: 0.62–0.99]) but not women (adjusted HR: 1.03 [95% CI: 0.78–1.37]), and among those aged ≥60 years (adjusted HR: 0.75 [95% CI: 0.59–0.96]) but not younger. We observed 111 ALS events (0.4 [95% CI: 0.4–0.5] per 10,000 person-years) among obesity patients and 431 ALS events (0.5 [95% CI: 0.5–0.6] per 10,000 person-years) among comparators. The adjusted HR was 0.88 (95% CI: 0.70–1.11). Conclusions Diagnoses of type 2 diabetes and obesity were associated with a reduced rate of ALS compared with general population comparators, particularly among men and patients aged 60 years or above. However, absolute rate differences were small., Background: Type 2 diabetes and obesity may be inversely associated with amyotrophic lateral sclerosis (ALS), but the evidence is controversial. Methods: Using Danish, nationwide registries (1980-2016), we identified patients with a diagnosis of type 2 diabetes (N = 295,653) and patients with a diagnosis of obesity (N = 312,108). Patients were matched (1:3) to persons from the general population on birth year and sex. We computed incidence rates and Cox regression derived hazard ratios (HRs) of a diagnosis of ALS. In multivariable analyses, HRs were controlled for sex, birth year, calendar year, and comorbidities. Results: We observed 168 incident cases of ALS (0.7 [95% confidence interval (CI): 0.6–0.8] per 10,000 person-years) among patients with type 2 diabetes and 859 incident cases of ALS (0.9 [95% CI: 0.9–1.0] per 10,000 person-years) among matched comparators. The adjusted HR was 0.87 (95% CI: 0.72–1.04). The association was present among men (adjusted HR: 0.78 [95% CI: 0.62–0.99]) but not women (adjusted HR: 1.03 [95% CI: 0.78–1.37]), and among those aged ≥60 years (adjusted HR: 0.75 [95% CI: 0.59–0.96]) but not younger. We observed 111 ALS events (0.4 [95% CI: 0.4–0.5] per 10,000 person-years) among obesity patients and 431 ALS events (0.5 [95% CI: 0.5–0.6] per 10,000 person-years) among comparators. The adjusted HR was 0.88 (95% CI: 0.70–1.11). Conclusions: Diagnoses of type 2 diabetes and obesity were associated with a reduced rate of ALS compared with general population comparators, particularly among men and patients aged 60 years or above. However, absolute rate differences were small.

Out-of-home care has been linked to excess mortality across the lifespan. We examined whether this association is modified by the age at first out-of-home care placement and the number of placements. In this population-based cohort study, we used register data covering all children born in Denmark between 1 and 1980 and 31 December 1999, totalling 1,111,193 individuals followed until 31 December 2018. We divided participants according to sex, out-of-home care status, age at first placement, and the number of placements. We estimated adjusted hazard ratios and hazard differences per 10,000 person-years for all-cause mortality and mortality due to suicide, accidents, and cancer between ages 18 and 39. 53,015 (4.8%) of the participants were placed in out-of-home care before age 18. The adjusted hazard ratio for all-cause mortality was 3.4 (95% CI 3.1–3.7) for males and 4.7 (4.0–5.4) for females, corresponding to 20.6 (19.0–22.2) and 10.3 (9.1–11.5) additional deaths per 10,000 individuals annually among males and females, respectively. Associations did not vary substantially according to age at first placement or the number of placements. Both males and females with a history of out-of-home care were more likely to die from suicide, accidents, and cancer compared with their peers. We show a markedly higher all-cause and cause-specific mortality among children who have been placed in out-of-home care, but contrary to our hypothesis, age at first placement and the number of placements did not modify this relation. These results warrant further investigation into potential target points for interventions that may prevent premature mortality in this group of disadvantaged individuals, Out-of-home care has been linked to excess mortality across the lifespan. We examined whether this association is modified by the age at first out-of-home care placement and the number of placements. In this population-based cohort study, we used register data covering all children born in Denmark between 1 and 1980 and 31 December 1999, totalling 1,111,193 individuals followed until 31 December 2018. We divided participants according to sex, out-of-home care status, age at first placement, and the number of placements. We estimated adjusted hazard ratios and hazard differences per 10,000 person-years for all-cause mortality and mortality due to suicide, accidents, and cancer between ages 18 and 39. 53,015 (4.8%) of the participants were placed in out-of-home care before age 18. The adjusted hazard ratio for all-cause mortality was 3.4 (95% CI 3.1–3.7) for males and 4.7 (4.0–5.4) for females, corresponding to 20.6 (19.0–22.2) and 10.3 (9.1–11.5) additional deaths per 10,000 individuals annually among males and females, respectively. Associations did not vary substantially according to age at first placement or the number of placements. Both males and females with a history of out-of-home care were more likely to die from suicide, accidents, and cancer compared with their peers. We show a markedly higher all-cause and cause-specific mortality among children who have been placed in out-of-home care, but contrary to our hypothesis, age at first placement and the number of placements did not modify this relation. These results warrant further investigation into potential target points for interventions that may prevent premature mortality in this group of disadvantaged individuals.

Aqueous organic redox flow batteries (AORFBs) have gained increased interest as a promising solution to store energy from sustainable energy sources. Inspired by naturally occurring bio-quinones, we here propose a new electrolyte based on the fungal compound phoenicin. Phoenicin was produced using the filamentous fungus Penicillium atrosanguineum at a concentration of 1.24 g L−1 liquid medium and extracted using ethyl acetate to a purity exceeding 95 %. The fungus may provide a benefit of high scalability of the biosynthesis-based production of the electroactive substance. Here, we demonstrate the performance of biologically produced phoenicin as a negative electrolyte in an RFB against ferro/ferricyanide, as a proof of concept, giving an initial capacity of 11.75 Ah L−1 and a capacity decay of 2.85 % day−1. For a deeper investigation of the battery setup, in situ attenuated total reflection infrared (ATR-IR) spectra of the phoenicin electrolyte were recorded. Symmetric cell cycling was performed to study the stability of this bio-based active material.

Why seek further education when working in the curatorial field? How does practice and theory feed off each other in curatorial work? And what is the status of the white cube? Do we need to move beyond this naturalised institution of exhibition making in order to engage with the urgencies of today? These are the main questions of the conversation between Line Sandvad Mengers and Nanna Balslev Strøjer, curators and graduates of the study programme MA in Curating at Aarhus University, and programme coordinator Trine Friis Sørensen.

Denne gang omhandler delresultaterne en undersøgelse af samtlige peer reviewed publikationer med en medforfatter fra Geocenter Danmark i perioden 2018-2021. Undersøgelsen viser blandt andet, at førsteforfatters køn er afgørende for kønssammensætningen for gruppen af medforfattere, og at langt de fleste publikationer fra Geocenter Danmark har en mandlig førsteforfatter samt en stor andel af mandlige medforfattere. Således viser undersøgelsen, at hele 30% af alle publikationer med en medforfatter fra Geocenter Danmark ikke har en eneste kvindelig medforfatter, mens det kun er 10% af publikationerne, hvor forfattergruppen består af mindst 50% kvindelige medforfattere.

’Kønsbalance på geofagene i Danmark’ er et forskningsprojekt finansieret af Geocenter Danmark. Projektet indsamler og analyserer kønsbaserede data på uddannelser, ansættelser, karrieretrin, publikationer, og fondsansøgninger i de danske geofag over tid. Foreløbige resultater fra forskningsprojektet viser, at der de sidste ti år har været en lige kønsfordeling eller endda en overvægt af kvinder fra bachelorer og helt op til post doc-niveau i de danske geofag. Til gengæld er kønsbalancen tiltagende skæv, des højere man bevæger sig op ad karrierestigen. Mest iøjnefaldende er den skæve kønsfordeling blandt professorer. Her ses det, at den nuværende kønsfordeling er 97-3 pct., hvilket dækker over, at der kun er én kvindelig professor i de danske geofag i dag.

Denne gang omhandler delresultaterne tidligere ph.d.-studerende fra Geocenter Danmark. Undersøgelsen baserer sig på 172 ph.d.-studerende, der er dimitteret i årene 2010-2017 og viser, at der i perioden har været en næsten ligelig kønsfordeling i færdiguddannede ph.d.’er fra Geocenter Danmark (gennemsnitligt 49,7% kvinder), hvilket ligger langt højere end end i de samlede naturvidenskabelige fag i Danmark. Desuden viser undersøgelsen, at mandlige ph.d.’er udgiver flere publikationer end kvindelige ph.d.’er, og at denne forskel især skyldes forskellen i antallet af publikationer udgivet som medforfatter. Vi vurderer at denne forskel skyldes at mandlige ph.d.-studerende i højere grad end deres kvindelige kollegaer tilskyndes at publicere deres resultater og oftere bliver inkluderet i publicerende netværk.

In early 2021, the SARS-CoV-2 lineage B.1.1.7 (Alpha variant) became dominant across large parts of the world. In Denmark, comprehensive and real-time test, contact-tracing, and sequencing efforts were applied to sustain epidemic control. Here, we use these data to investigate the transmissibility, introduction, and onward transmission of B.1.1.7 in Denmark. We analyzed a comprehensive set of 60,178 SARS-CoV-2 genomes generated from high-throughput sequencing by the Danish COVID-19 Genome Consortium, representing 34% of all positive cases in the period 14 November 2020 to 7 February 2021. We calculated the transmissibility of B.1.1.7 relative to other lineages using Poisson regression. Including all 1976 high-quality B.1.1.7 genomes collected in the study period, we constructed a time-scaled phylogeny, which was coupled with detailed travel history and register data to outline the introduction and onward transmission of B.1.1.7 in Denmark. In a period with unchanged restrictions, we estimated an increased B.1.1.7 transmissibility of 58% (95% CI: [56%, 60%]) relative to other lineages. Epidemiological and phylogenetic analyses revealed that 37% of B.1.1.7 cases were related to the initial introduction in November 2020. The relative number of cases directly linked to introductions varied between 10 and 50% throughout the study period. Our findings corroborate early estimates of increased transmissibility of B.1.1.7. Both substantial early expansion when B.1.1.7 was still unmonitored and continuous foreign introductions contributed considerably to case numbers. Finally, our study highlights the benefit of balanced travel restrictions and self-isolation procedures coupled with comprehensive surveillance efforts, to sustain epidemic control in the face of emerging variants.

Thermostable cellulases from glycoside hydrolase family 7 (GH7) are the main components of enzymatic mixtures for industrial saccharification of lignocellulose. Activity improvement of these enzymes via rational design is a promising strategy to alleviate the industrial costs, but it requires detailed structural knowledge. While substantial biochemical and structural data is available for GH7 cellobiohydrolases, endoglucanases are more elusive and only few structures have been solved so far. Here we report a new crystal structure and biochemical characterization of a thermostable endoglucanase from the thermophilic ascomycete Rasamsonia emersonii, ReCel7B. The enzyme was compared with the homologous endoglucanase from the mesophilic model ascomycete Trichoderma reesei (TrCel7B), which unlike ReCel7B possesses an additional carbohydrate binding module (CBM). With a temperature optimum of 80°C, ReCel7B displayed a number of differences in activity and ability to synergize with cellobiohydrolases compared to TrCel7B. We improved both binding and kinetics in a chimeric variant of ReCel7B and a CBM, while we observe the opposite effect when the CBM was removed in TrCel7B. The crystal structure of ReCel7B was determined at 2.48 Å resolution, with Rwork and Rfree factors of 0.182 and 0.206, respectively. Structural analyses revealed that ReCel7B has increased rigidity in a number of peripheral loops compared to TrCel7B and fewer aromatics in the substrate binding cleft. An increased number of glycosylations were identified in ReCel7B and we propose a stabilizing mechanism for one of the glycans. Global structure-function interpretations of ReCel7B highlight the differences in temperature stability, turnover, binding and cellulose accessibility in GH7 endoglucanases.

Understanding pH effect of cellulolytic enzymes are of great technological importance. In this study, we have examined the influence of pH on activity and stability for central cellulases (Cel7A, Cel7B, Cel6A from Trichoderma reesei and Cel7A from Rasamsonia emersonii). We systematically changed pH from 2 to 7, temperature from 20 - 70°C, and used both soluble (pNPL) and insoluble (Avicel) substrates at different concentrations. Collective interpretation of these data provided new insights. An unusual tolerance to acidic conditions was observed for both investigated Cel7As, but only on real insoluble cellulose. In contrast, pH-profiles on pNPL were bell-shaped with strong loss of activity both above and below the optimal pH for all four enzymes. On a practical level, these observations calls for caution of the common practice of using soluble substrates for general characterization of pH effects on cellulase activity. Kinetic modeling of the experimental data suggested that the nucleophile of Cel7A experiences a strong downward shift in pKa upon complexation with an insoluble substrate. This shift was less pronounced for Cel7B, Cel6A and for Cel7A acting on soluble substrate, and we hypothesize that these differences are related to the accessibility of water to the binding region of the Michaelis complex.

Glycoside hydrolase family 7 (GH7) cellulases are some of the most efficient degraders of cellulose, making them particularly relevant for industries seeking to produce renewable fuels from lignocellulosic biomass. The secretome of the cellulolytic model fungus Trichoderma reesei contains two GH7s, termed TrCel7A and TrCel7B. Despite having high structural and sequence similarities, the two enzymes are functionally quite different. TrCel7A is an exolytic, processive cellobiohydrolase (CBH), with high activity on crystalline cellulose, whereas TrCel7B is an endoglucanase (EG) with a preference for more amorphous cellulose. At the structural level, these functional differences are usually ascribed to the flexible loops that cover the substrate-binding areas. TrCel7A has an extensive tunnel created by eight peripheral loops, and the absence of four of these loops in TrCel7B makes its catalytic domain a more open cleft. To investigate the structure-function relationships of these loops, here we produced and kinetically characterized several variants in which four loops unique to TrCel7A were individually deleted to resemble the arrangement in the TrCel7B structure. Analysis of a range of kinetic parameters consistently indicated that the B2 loop, covering the substrate-binding subsites -3 and -4 in TrCel7A, was a key determinant for the difference in CBH- or EG-like behavior between TrCel7A and TrCel7B. Conversely, the B3 and B4 loops, located closer to the catalytic site in TrCel7A, were less important for these activities. We surmise that these results could be useful both in further mechanistic investigations and for guiding engineering efforts of this industrially important enzyme family.