Cultivation of \u3cem\u3eTropheryma whipplei\u3c/em\u3e from Cerebrospinal Fluid

Whipple disease (WD) is a systemic disorder caused by the bacterium Tropheryma whipplei. Since the recognition of a bacterial etiology in 1961, many attempts have been made to cultivate this bacterium in vitro. It was eventually isolated, in 2000, from an infected heart valve, in coculture with human fibroblasts. Here we report the isolation of 2 new strains of T. whipplei from cerebrospinal fluid (CSF) of 2 patients with intestinal WD but no neurological signs or symptoms. One culture-positive specimen was obtained before treatment; the other was obtained 12 months after discontinuation of therapy, at a time of intestinal remission. In both cases, 15 passages of the cultures were completed over 17 months. Bacterial growth was measured by quantitative polymerase chain reaction, which suggested a generation time of 4 days. Staining with YO-PRO nucleic-acid dye showed characteristic rod-shaped bacteria arranged in chains. Fluorescent in situ hybridization with a T. whipplei–specific oligonucleotide probe, a broad-range bacterial probe, and a nonspecific nucleicacid stain indicated that all visible bacteria were T. whipplei. Scanning electron microscopy and transmission electron microscopy showed both intracellular and extracellular bacteria. This first isolation of T. whipplei from CSF provides clear evidence of viable bacteria in the central nervous system in individuals with WD, even after prolonged antibiotic therapy

Persistent detwinning of iron pnictides by small magnetic fields

Our comprehensive study on EuFe$_2$As$_2$ reveals a dramatic reduction of magnetic detwinning fields compared to other AFe$_2$As$_2$ (A = Ba, Sr, Ca) iron pnictides by indirect magneto-elastic coupling of the Eu$^{2+}$ ions. We find that only 0.1T are sufficient for persistent detwinning below the local Eu$^{2+}$ ordering; above $T_\text{Eu}$ = 19K, higher fields are necessary. Even after the field is switched off, a significant imbalance of twin domains remains constant up to the structural and electronic phase transition (190K). This persistent detwinning provides the unique possibility to study the low temperature electronic in-plane anisotropy of iron pnictides without applying any symmetrybreaking external force.Comment: accepted by Physical Review Letter

Cultivation of Tropheryma whipplei from cerebrospinal fluid

Whipple disease (WD) is a systemic disorder caused by the bacterium Tropheryma whipplei. Since the recognition of a bacterial etiology in 1961, many attempts have been made to cultivate this bacterium in vitro. It was eventually isolated, in 2000, from an infected heart valve, in coculture with human fibroblasts. Here we report the isolation of 2 new strains of T. whipplei from cerebrospinal fluid (CSF) of 2 patients with intestinal WD but no neurological signs or symptoms. One culture-positive specimen was obtained before treatment; the other was obtained 12 months after discontinuation of therapy, at a time of intestinal remission. In both cases, 15 passages of the cultures were completed over 17 months. Bacterial growth was measured by quantitative polymerase chain reaction, which suggested a generation time of 4 days. Staining with YO-PRO nucleic-acid dye showed characteristic rod-shaped bacteria arranged in chains. Fluorescent in situ hybridization with a T. whipplei–specific oligonucleotide probe, a broad-range bacterial probe, and a nonspecific nucleicacid stain indicated that all visible bacteria were T. whipplei. Scanning electron microscopy and transmission electron microscopy showed both intracellular and extracellular bacteria. This first isolation of T. whipplei from CSF provides clear evidence of viable bacteria in the central nervous system in individuals with WD, even after prolonged antibiotic therapy

Upper critical magnetic field in K0.83Fe1.83Se2 and Eu0.5K0.5Fe2As2 single crystals

The H-T phase diagrams of single crystalline electron-doped K0.83Fe1.83Se2 (KFS1), K0.8Fe2Se2 (KFS2) and hole-doped Eu0.5K0.5Fe2As2 (EKFA) have been deduced from tunnel diode oscillator-based contactless measurements in pulsed magnetic fields up to 57 T for the inter-plane (H//c) and in-plane (H//ab) directions. The temperature dependence of the upper critical magnetic field Hc2(T) relevant to EFKA is accounted for by the Pauli model including an anisotropic Pauli paramagnetic contribution (\mu_BHp=114 T for H//ab and 86 T for H//c). This is also the case of KFS1 and KFS2 for H//ab whereas a significant upward curvature, accounted for by a two-gap model, is observed for H//c. Despite the presence of antiferromagnetic lattice order within the superconducting state of the studied compounds, no influence of magnetic ordering on the temperature dependence of Hc2(T) is observed.Comment: 9 pages, 5 figures. arXiv admin note: text overlap with arXiv:1104.561

Physico-chemical behaviour of underground waters after the october 1, 1995 Dinar earthquake, SW Turkey

On the evening of October 1, 1995, a MS46.1 earthquake destroyed the city of Dinar, SW Turkey. Within 48 hours after the main shock, a team of the German Earthquake Task Force arrived in the area to investigate possible earthquake-related changes in the physico-chemical composition of shallow and deep groundwaters. A mapping was performed to characterise different groundwater types and a continuously monitoring station was installed within the geothermal field of Afyon. Repeated measurements, performed 1, 6, 12 and 18 months after the event, reveal post-seismic changes in water discharge, water temperature, and conductivity. We will focus on the changes of spring water discharge observed in the vicinity of the epicentre. In the first month after the earthquake the groundwater discharge increased at springs located within the down-thrown block, whereas a slight decrease was observed at sites on the hanging wall

Lessons from Love-Locks: The archaeology of a contemporary assemblage

This document is the Accepted Manuscript version. The final, definitive version of this paper has been published in Journal of Material Culture, November 2017, published by SAGE Publishing, All rights reserved.Loss of context is a challenge, if not the bane, of the ritual archaeologist’s craft. Those who research ritual frequently encounter difficulties in the interpretation of its often tantalisingly incomplete material record. Careful analysis of material remains may afford us glimpses into past ritual activity, but our often vast chronological separation from the ritual practitioners themselves prevent us from seeing the whole picture. The archaeologist engaging with structured deposits, for instance, is often forced to study ritual assemblages post-accumulation. Many nuances of its formation, therefore, may be lost in interpretation. This paper considers what insights an archaeologist could gain into the place, people, pace, and purpose of deposition by recording an accumulation of structured deposits during its formation, rather than after. To answer this, the paper will focus on a contemporary depositional practice: the love-lock. This custom involves the inscribing of names/initials onto a padlock, its attachment to a bridge or other public structure, and the deposition of the corresponding key into the water below; a ritual often enacted by a couple as a statement of their romantic commitment. Drawing on empirical data from a three-year diachronic site-specific investigation into a love-lock bridge in Manchester, UK, the author demonstrates the value of contemporary archaeology in engaging with the often enigmatic material culture of ritual accumulations.Peer reviewe

Screening chimeric GAA variants in preclinicalstudy results in hematopoietic stem cell genetherapy candidate vectors for Pompe disease

Pompe disease is a rare genetic neuromuscular disorder caused by acid α-glucosidase (GAA) deficiency resulting in lysosomal glycogen accumulation and progressive myopathy. Enzyme replacement therapy, the current standard of care, penetrates poorly into the skeletal muscles and the peripheral and central nervous system (CNS), risks recombinant enzyme immunogenicity, and requires high doses and frequent infusions. Lentiviral vector-mediated hematopoietic stem and progenitor cell (HSPC) gene therapy was investigated in a Pompe mouse model using a clinically relevant promoter driving nine engineered GAA coding sequences incorporating distinct peptide tags and codon optimizations. Vectors solely including glycosylation-independent lysosomal targeting tags enhanced secretion and improved reduction of glycogen, myofiber, and CNS vacuolation in key tissues, although GAA enzyme activity and protein was consistently lower compared with native GAA. Genetically modified microglial cells in brains were detected at low levels but provided robust phenotypic correction. Furthermore, an amino acid substitution introduced in the tag reduced insulin receptor-mediated signaling with no evidence of an effect on blood glucose levels in Pompe mice. This study demonstrated the therapeutic potential of lentiviral HSPC gene therapy exploiting optimized GAA tagged coding sequences to reverse Pompe disease pathology in a preclinical mouse model, providing promising vector candidates for further investigation