Domain-wall dynamics in 4C pyrrhotite at low temperature

Monoclinic 4C pyrrhotite (Fe7S8) is ferrimagnetic due to an ordered defect structure with alternating vacancy and vacancy-free sublattices. Its low-temperature magnetic transition near 35 K is characterized by the distinct increase in coercivity and remanent magnetization. The increase of these parameters has been attributed to changes in the domain wall structure. We present static and dynamic magnetization data of a powder sample to study the domain-wall dynamics across the low-temperature transition. The amplitude-dependent ac susceptibility and the ferromagnetic resonance spectroscopy indicate that the hardening of the domain-wall pinning at the transition occurs simultaneously with the decrease in initial saturation remanent magnetization. These two effects are explained by the enhanced inhomogeneity of the bulk material caused by the persistency of the ordered vacancies and by newly formed defects due to localized distortion of Fe(II) sites in the vacancy-free sublattice. The generated localized defects are the link between the domain wall dynamics and the low-temperature transition in 4C pyrrhotit

Spatial distribution of white matter degenerative lesions and cognitive dysfunction in relapsing-remitting multiple sclerosis patients

Aim. The aim of this study was to assess degenerative lesion localisation in the course of relapsing-remitting multiple sclerosis (RRMS) and to identify the association between localisation and the frequency of T1-hypointense lesions (black holes) with cognitive dysfunction. We also searched for neuroradiological predictors of cognitive dysfunction in patients. The clinical rationale for the study was previous research, and our own findings suggest that lesion localisation plays an important role in cognitive performance and neurological disability of MS patients. Material and methods. Forty-two patients were included in the study. All subjects underwent neuropsychological examination using Raven’s Coloured Progressive Matrices, a naming task from the Brief Repeatable Battery of Neuropsychological Tests, and attention to detail tests. Magnetic resonance imaging (MRI) was acquired on 1.5 Tesla scanner and black holes were manually segmented on T1-weighted volumetric images using the FMRIB Software Library. Linear regression was applied to establish a relationship between black hole volume per lobe and cognitive parameters. Bonferroni correction of voxelwise analysis was used to correct for multiple comparisons. Results. The following associations between black hole volume and cognition were identified: frontal lobes black hole volume was associated with phonemic verbal fluency (t = –4.013, p < 0.001), parietal black hole volume was associated with attention (t = –3.776, p < 0.001), and parietal and temporal black hole volumes were associated with nonverbal intelligence (p < 0.001). The volume of parietal black holes was the best predictor of cognitive dysfunction. Conclusions. Our approach, including measurement of focal axonal loss based on T1-volumetric MRI sequence and brief neuropsychological assessment, might improve personalised diagnostic and therapeutic decisions in clinical practice

Orbital and millenial-scale environmental changes between 64 and 25 ka BP recorded in Black Sea sediments

High-resolution pollen and dinoflagellate cyst records from sediment core M72/5-25-GC1 were used to reconstruct vegetation dynamics in northern Anatolia and surface conditions of the Black Sea between 64 and 20 ka BP. During this period, the dominance of Artemisia in the pollen record indicates a steppe landscape and arid climate conditions. However, the concomitant presence of temperate arboreal pollen suggests the existence of glacial refugia in northern Anatolia. Long-term glacial vegetation dynamics reveal two major arid phases ~64–55 and 40–32 ka BP, and two major humid phases ~54–45 and 28–20 ka BP, correlating with higher and lower summer insolation, respectively. Dansgaard–Oeschger (D–O) cycles are clearly indicated by the 25-GC1 pollen record. Greenland interstadials are characterized by a marked increase in temperate tree pollen, indicating a spread of forests due to warm/wet conditions in northern Anatolia, whereas Greenland stadials reveal cold and arid conditions as indicated by spread of xerophytic biomes. There is evidence for a phase lag of ~500 to 1500 yr between initial warming and forest expansion, possibly due to successive changes in atmospheric circulation in the North Atlantic sector. The dominance of Pyxidinopsis psilata and Spiniferites cruciformis in the dinocyst record indicates brackish Black Sea conditions during the entire glacial period. The decrease of marine indicators (marine dinocysts, acritarchs) at ~54 ka BP and increase of freshwater algae (Pediastrum, Botryococcus) from 32 to 25 ka BP reveals freshening of the Black Sea surface water. This freshening is possibly related to humid phases in the region, to connection between Caspian Sea and Black Sea, to seasonal freshening by floating ice, and/or to closer position of river mouths due to low sea level. In the southern Black Sea, Greenland interstadials are clearly indicated by high dinocyst concentrations and calcium carbonate content, as a result of an increase in primary productivity. Heinrich events show a similar impact on the environment in the northern Anatolia/Black Sea region as Greenland stadials

Bias-free photoelectrochemical water splitting with photosystem II on a dye-sensitized photoanode wired to hydrogenase

Natural photosynthesis stores sunlight in chemical energy carriers, but it has not evolved for the efficient synthesis of fuels, such as H2. Semi-artificial photosynthesis combines the strengths of natural photosynthesis with synthetic chemistry and materials science to develop model systems that overcome Nature’s limitations, such as low-yielding metabolic pathways and non-complementary light absorption by Photosystem (PS) I and II. Here, we report a bias-free semi-artificial tandem platform that wires PSII to hydrogenase for overall water splitting. This photoelectrochemical cell integrated the red and blue light-absorber PSII with a green light-absorbing diketopyrrolopyrrole dye-sensitised TiO2 photoanode enabling complementary panchromatic solar light absorption. Effective electronic communication at the enzyme-material interface was engineered using an Os complex-modified redox polymer on a hierarchically-structured TiO2. This system provides a design protocol for bias-free semi-artificial Z-schemes in vitro and provides an extended toolbox of biotic and abiotic components to re-engineer photosynthetic pathways.ERC Consolidator Grant, EPSRC (nanoDTC, DTA studentship), Christian Doppler Research Association, OMV Group, Royal Society Newton International Fellowship, Cluster of Excellence RESOLV (DFG) and European Unions' Horizon 202

Putative Cooperative ATP-DnaA Binding to Double-Stranded DnaA Box and Single-Stranded DnaA-Trio Motif upon Helicobacter pylori Replication Initiation Complex Assembly

oriC is a region of the bacterial chromosome at which the initiator protein DnaA interacts with specific sequences, leading to DNA unwinding and the initiation of chromosome replication. The general architecture of oriCs is universal; however, the structure of oriC and the mode of orisome assembly differ in distantly related bacteria. In this work, we characterized oriC of Helicobacter pylori, which consists of two DnaA box clusters and a DNA unwinding element (DUE); the latter can be subdivided into a GC-rich region, a DnaA-trio and an AT-rich region. We show that the DnaA-trio submodule is crucial for DNA unwinding, possibly because it enables proper DnaA oligomerization on ssDNA. However, we also observed the reverse effect: DNA unwinding, enabling subsequent DnaA–ssDNA oligomer formation—stabilized DnaA binding to box ts1. This suggests the interplay between DnaA binding to ssDNA and dsDNA upon DNA unwinding. Further investigation of the ts1 DnaA box revealed that this box, together with the newly identified c-ATP DnaA box in oriC1, constitute a new class of ATP–DnaA boxes. Indeed, in vitro ATP–DnaA unwinds H. pylori oriC more efficiently than ADP–DnaA. Our results expand the understanding of H. pylori orisome formation, indicating another regulatory pathway of H. pylori orisome assembly

Functional analysis and transcriptional output of the Göttingen minipig genome

In the past decade the Göttingen minipig has gained increasing recognition as animal model in pharmaceutical and safety research because it recapitulates many aspects of human physiology and metabolism. Genome-based comparison of drug targets together with quantitative tissue expression analysis allows rational prediction of pharmacology and cross-reactivity of human drugs in animal models thereby improving drug attrition which is an important challenge in the process of drug development.; Here we present a new chromosome level based version of the Göttingen minipig genome together with a comparative transcriptional analysis of tissues with pharmaceutical relevance as basis for translational research. We relied on mapping and assembly of WGS (whole-genome-shotgun sequencing) derived reads to the reference genome of the Duroc pig and predict 19,228 human orthologous protein-coding genes. Genome-based prediction of the sequence of human drug targets enables the prediction of drug cross-reactivity based on conservation of binding sites. We further support the finding that the genome of Sus scrofa contains about ten-times less pseudogenized genes compared to other vertebrates. Among the functional human orthologs of these minipig pseudogenes we found HEPN1, a putative tumor suppressor gene. The genomes of Sus scrofa, the Tibetan boar, the African Bushpig, and the Warthog show sequence conservation of all inactivating HEPN1 mutations suggesting disruption before the evolutionary split of these pig species. We identify 133 Sus scrofa specific, conserved long non-coding RNAs (lncRNAs) in the minipig genome and show that these transcripts are highly conserved in the African pigs and the Tibetan boar suggesting functional significance. Using a new minipig specific microarray we show high conservation of gene expression signatures in 13 tissues with biomedical relevance between humans and adult minipigs. We underline this relationship for minipig and human liver where we could demonstrate similar expression levels for most phase I drug-metabolizing enzymes. Higher expression levels and metabolic activities were found for FMO1, AKR/CRs and for phase II drug metabolizing enzymes in minipig as compared to human. The variability of gene expression in equivalent human and minipig tissues is considerably higher in minipig organs, which is important for study design in case a human target belongs to this variable category in the minipig. The first analysis of gene expression in multiple tissues during development from young to adult shows that the majority of transcriptional programs are concluded four weeks after birth. This finding is in line with the advanced state of human postnatal organ development at comparative age categories and further supports the minipig as model for pediatric drug safety studies.; Genome based assessment of sequence conservation combined with gene expression data in several tissues improves the translational value of the minipig for human drug development. The genome and gene expression data presented here are important resources for researchers using the minipig as model for biomedical research or commercial breeding. Potential impact of our data for comparative genomics, translational research, and experimental medicine are discussed

67. Radical radiotherapy of muscle-invading bladder cancer (BC): a retrospective analysis of 49 patients

Growing interest in the use of combined modality approaches for bladder-sparing procedures force radiation oncologists to optimise methods of radical radiotherapy. Since treatment policies have changed considerably over the last years, in this retrospective study we analysed feasibility of radical radiotherapy and outcomes of patients treated in our institution between 1992 and 2000. Study group comprised 49 consecutive BC patients aged 43 to 80 years (median 71), including three cases with clinically involved pelvic lymph nodes. There were 45 urothelial, and four other types of cancer (grade 1- four, 2 – 21, 3-nine, and unknown -14 cases). Six patients were referred for radiotherapy after nonradical operation. Treatment was delivered with the use of 60Co or LA five days a week, without planned interruptions. Thirty-two patients received elective irradiation of the pelvic lymph nodes to the dose 40 to 48 Gy, followed by the boost to the bladder to the total dose 60 to 66 Gy. Seventeen patients received total dose of 58 to 62 Gy to the bladder and perivesical tissue. Fraction doses ranged from 1.8 to 2.0 Gy. Treatment was prematurely stopped due to disease progression (PD), patient refusal, uraemia, in one case each, and intractable diarrhoea in six cases. After a median follow-up of 14 months (range 1 – 102) 23 patients died of PD. Median survival in the entire group is 159 months. Results of this study confirm relative efficacy of radiotherapy in BC. Further refinement of radiotherapy techniques is warranted to improve the outcome