Host-guided migration allows targeted introduction of neurons into the embryonic brain

AbstractThe stereotyped positions occupied by individual classes of neurons are a fundamental characteristic of CNS cytoarchitecture. To study the regulation of neuronal positioning, we injected genetically labeled neural precursors derived from dorsal and ventral mouse forebrain into the telencephalic vesicles of embryonic rats. Cells from both areas were found to participate in the generation of telencephalic, diencephalic, and mesencephalic brain regions. Donorderived neurons populated the host brain in distinct patterns and acquired phenotypic features appropriate for their final location. These observations indicate that neuronal migration and differentiation are predominantly regulated by non-cell-autonomous signals. Exploiting this phenomenon, intrauterine transplantation allows generation of controlled chimerism in the mammalian brain

»Und dann hab’ ich gemerkt, wie viel Spaß das auch macht«

Rollstühle sind Fortbewegungsmittel. Sie haben vier Räder, einen Metallrahmen und einen Stoffbezug mit Polster. Rollstühle sind praktisch und nützlich – eigentlich. Doch in dominanten Diskursen zu Behinderung umgibt Rollstühle ein Nimbus des Problems, der Angst, des sozial Alarmierenden. Rollstühle signalisieren etwas, z.B. Passivität, Gefangensein und Abhängigkeit. Demgegenüber stehen Diskurse, die Rollstühle als befreiende, alltägliche und einverleibte Hilfsmittel sehen, die ein selbstbestimmtes Leben (wieder) ermöglichen. Dennoch zögern viele stark gehbeeinträchtigte Menschen Jahre, bevor sie sich für die Nutzung eines Rollstuhls entscheiden. Dieser Beitrag beschäftigt sich mit Prozessen der Aneignung von Rollstühlen und ihren gesellschaftlichen Rahmenbedingungen. Er schließt vorläufige Ergebnisse einer qualitativen Befragung gehbeeinträchtigter Menschen mit ein und geht Diskursen im Kontext von Disziplinierung und einer Verinnerlichung von Stigma und »ableism« nach.Wheelchairs are means of transportation. They have four wheels, a metal frame, a fabric seating and a seat cushion. Wheelchairs can be seen as convenient and useful. But in dominant discourses wheelchairs are overshadowed by the problematic, by fear and social alarm. Wheelchairs signal something, e.g. passivity, dependency, being trapped. In opposition to this there are discourses that promote the wheelchair as a liberating, mundane and as an embodied assistive device that (re-)enables an independent life. However, a lot of severely walking impaired people hesistate for years, until they opt for using a wheelchair. This contribution is looking at wheelchair acquisition and acceptance processes and their societal framework. It includes preliminary results of a qualitative interview study with people with walking impairments and tries to unravel discourses of disciplining and of the internalisation of stigma and ableism

Der Versuch zur Enthinderung der Wissenschaft: ein Überblick über die Disabilitiy Studies in den USA aus der Sicht einer Gaststudentin

Das in Deutschland noch weitgehend unbekannte Fach Disability Studies ist in den USA bereits seit etwa zehn Jahren als Forschungsrichtung anerkannt und an einigen wenigen Universitäten vertreten. Der Text berichtet über die Erfahrung, Disability Studies im Rahmen eines Auslandsjahrs an einer Chicagoer Universität zu studieren und nimmt dabei Bezug auf die Entwicklung des Faches in den USA, seine derzeitigen Grundansätze und -debatten, sowie auf die Zusammensetzung und Interessen amerikanischer Studierender der Disability Studies. Dabei wird sowohl auf die allgemeinen Besonderheiten des Studiums in den USA, als auch auf den Hintergrund der Disability Studies, aus einer sozialen Bewegung heraus entstanden zu sein, eingegangen. Abschließend werden Perspektiven für Disability Studies in Deutschland aufgezeigt

Synthesis, characterization, biological activity and equilibrium studies of cadmium(II) with 2,6-diaminopyridine and various bio-relevant ligands

The complexing properties of 2,6-diaminopyridine (DAP) with cadmium(II) were investigated  via measuring pH (i.e., pH-metrically). Binary and ternary complexes of Cd(II) involving DAP and various biologically relevant ligands are investigated. The ligands used (L) were  amino acids, dicarboxylic acids, amides and DNA unit constituents. The ternary complexes are formed by simultaneous reactions. The results showed the formation of Cd(DAP)(L) complexes with amino acids and dicarboxylic acids. Amides form both Cd(DAP)(L) complex and the corresponding deprotonated amide species Cd(DAP)(LH-1). The concentration distributions of the various complex species formed in solution were also evaluated as a function of pH. The effect of dioxane as a solvent on the protonation constant of DAP and the formation constants of Cd(II)-DAP complexes were discussed. The solid complexes [Cd(DAP)L)] where L = methionine and glycine, were isolated and characterized. The isolated solid complexes have also been screened for their antimicrobial activities against some selected bacteria and fungi. The activity data show that the complexes are found to have antibacterial and antifungal activity

Probing the interface in a human co-chaperonin heptamer: residues disrupting oligomeric unfolded state identified

BACKGROUND: The co-chaperonin protein 10 (cpn10) assists cpn60 in the folding of nonnative polypeptides in a wide range of organisms. All known cpn10 molecules are heptamers of seven identical subunits that are linked together by β-strand interactions at a large and flexible interface. Unfolding of human mitochondrial cpn10 in urea results in an unfolded heptameric state whereas GuHCl additions result in unfolded monomers. To address the role of specific interface residues in the assembly of cpn10 we prepared two point-mutated variants, in each case removing a hydrophobic residue positioned at the subunit-subunit interface. RESULTS: Replacing valine-100 with a glycine (Val100Gly cpn10) results in a wild-type-like protein with seven-fold symmetry although the thermodynamic stability is decreased and the unfolding processes in urea and GuHCl both result in unfolded monomers. In sharp contrast, replacing phenylalanine-8 with a glycine (Phe8Gly cpn10) results in a protein that has lost the ability to assemble. Instead, this protein exists mostly as unfolded monomers. CONCLUSIONS: We conclude that valine-100 is a residue important to adopt an oligomeric unfolded state but it does not affect the ability to assemble in the folded state. In contrast, phenylalanine-8 is required for both heptamer assembly and monomer folding and therefore this mutation results in unfolded monomers at physiological conditions. Despite the plasticity and large size of the cpn10 interface, our observations show that isolated interface residues can be crucial for both the retention of a heptameric unfolded structure and for subunit folding

Formation and Stabilization of Persistent Free Radicals

We demonstrate that stable and relatively unreactive “environmentally persistent free radicals (PFRs)” can be readily formed in the post-flame and cool-zone regions of combustion systems and other thermal processes. These resonance-stabilized radicals, including semiquinones, phenoxyls, and cyclopentadienyls, can be formed by the thermal decomposition of molecular precursors including catechols, hydroquinones and phenols. Association with the surfaces of fine particles imparts additional stabilization to these radicals such that they can persist almost indefinitely in the environment. A mechanism of chemisorption and electron transfer from the molecular adsorbate to a redox-active transition metal or other receptor is shown through experiment, and supported by molecular orbital calculations, to result in PFR formation. Both oxygen-centered and carbon-centered PFRs are possible that can significantly affect their environmental and biological reactivity

Diagnostic Utility of Temporal Muscle Thickness as a Monitoring Tool for Muscle Wasting in Neurocritical Care

Temporalis muscle (TM) atrophy has emerged as a potential biomarker for muscle wasting. However, its diagnostic utility as a monitoring tool in intensive care remains uncertain. Hence, the objective of this study was to evaluate the diagnostic value of sequential ultrasound- and computed tomography (CT)-based measurements of TM thickness (TMT). With a prospective observational design, we included 40 patients without preexisting sarcopenia admitted to a neurointensive care unit. TMT measurements, performed upon admission and serially every 3–4 days, were correlated with rectus femoris muscle thickness (RFT) ultrasound measurements. Interrater reliability was assessed by Bland Altmann plots and intraclass correlation coefficient (ICC). Analysis of variance was performed in subgroups to evaluate differences in the standard error of measurement (SEM). RFT decline was paralleled by ultrasound- as well as CT-based TMT measurements (TMT to RFT: r = 0.746, p < 0.001; CT-based TMT to ultrasound-based RFT: r = 0.609, p < 0.001). ICC was 0.80 [95% CI 0.74, 0.84] for ultrasound-based assessment and 0.90 [95% CI 0.88, 0.92] for CT-based TMT measurements. Analysis of variance for BMI, Heckmatt score, fluid balance, and agitation showed no evidence of measurement errors in these subgroups. This study demonstrates the clinical feasibility and utility of ultrasound- and CT-based TMT measurements for the assessment of muscle wasting

Inflammatory and cytotoxic responses of an alveolar-capillary coculture model to silica nanoparticles: Comparison with conventional monocultures

<p>Abstract</p> <p>Background</p> <p>To date silica nanoparticles (SNPs) play an important role in modern technology and nanomedicine. SNPs are present in various materials (tyres, electrical and thermal insulation material, photovoltaic facilities). They are also used in products that are directly exposed to humans such as cosmetics or toothpaste. For that reason it is of great concern to evaluate the possible hazards of these engineered particles for human health. Attention should primarily be focussed on SNP effects on biological barriers. Accidentally released SNP could, for example, encounter the alveolar-capillary barrier by inhalation. In this study we examined the inflammatory and cytotoxic responses of monodisperse amorphous silica nanoparticles (aSNPs) of 30 nm in size on an <it>in vitro </it>coculture model mimicking the alveolar-capillary barrier and compared these to conventional monocultures.</p> <p>Methods</p> <p>Thus, the epithelial cell line, H441, and the endothelial cell line, ISO-HAS-1, were used in monoculture and in coculture on opposite sides of a filter membrane. Cytotoxicity was evaluated by the MTS assay, detection of membrane integrity (LDH release), and TER (Transepithelial Electrical Resistance) measurement. Additionally, parameters of inflammation (sICAM-1, IL-6 and IL-8 release) and apoptosis markers were investigated.</p> <p>Results</p> <p>Regarding toxic effects (viability, membrane integrity, TER) the coculture model was less sensitive to apical aSNP exposure than the conventional monocultures of the appropriate cells. On the other hand, the <it>in vitro </it>coculture model responded with the release of inflammatory markers in a much more sensitive fashion than the conventional monoculture. At concentrations that were 10-100fold less than the toxic concentrations the apically exposed coculture showed a release of IL-6 and IL-8 to the basolateral side. This may mimic the early inflammatory events that take place in the pulmonary alveoli after aSNP inhalation. Furthermore, a number of apoptosis markers belonging to the intrinsic pathway were upregulated in the coculture following aSNP treatment. Analysis of the individual markers indicated that the cells suffered from DNA damage, hypoxia and ER-stress.</p> <p>Conclusion</p> <p>We present evidence that our <it>in vitro </it>coculture model of the alveolar-capillary barrier is clearly advantageous compared to conventional monocultures in evaluating the extent of damage caused by hazardous material encountering the principle biological barrier in the lower respiratory tract.</p