1,248 research outputs found
Crystal structure of a synthetic cyclodecapeptide for template-assembled synthetic protein design
No full textThe structural prototype of a new generation of regioselectively addressable functionalized templates (RAFTs) for use in protein de novo design has been synthesized and crystallized. The structure of the aromatically substituted cyclodecapeptide was determined by X-ray diffraction; it consists of an antiparallel β sheet spanned by heterochirally induced type II′ β turns, similar to that observed in gramicidin S. The three-dimensional structure of the artificial template was also examined by an NMR spectroscopic analysis in solution and shown to be compatible with a β-sheet plane suitable for accommodating secondary functional peptide fragments for the synthesis of template-assembled synthetic proteins (TASPs)
CD4-helper-independent antiviral function of CD8-positive memory T lymphocytes derived from latently infected donors
No full textThe ability of memory T lymphocytes derived from latently infected mice to control murine cytomegalovirus disease in the immunocompromised host was studied by adoptive transfer experiments. At a stage of pathogenesis when virus had already colonized target tissues, a therapeutic antiviral function could be ascribed to the CD8+ subset. This in vivo function was not restricted to sites in which intravenously infused lymphocytes usually are trapped or home in, such as the lungs or the spleen, respectively, but was also evident in the adrenal glands, a site to which antiviral effector cells have to specifically migrate. Specific infiltration of adrenal gland cortical tissue by donor-derived CD8+ memory T lymphocytes was demonstrated. CD4+ memory T lymphocytes had no antiviral effect by themselves and also were not required for the function of the CD8+ effector cells in this short-term immunotherapy model. These findings should help settle the debate about which subset of T lymphocytes comprises the effector cells that can directly control cytomegalovirus infection in the murine model system
Computational evidence for structural consequences of kiteplatin damage on DNA
No full textThe reaction of the potential anticancer drug
kiteplatin, cis-[PtCl2(cis-1,4-DACH)], with oligomers of
single- and double-stranded DNA ranging from 2 to 12
base pairs in length was performed as a model for DNA
interaction. The potential for conformational flexibility of
single-stranded adducts was examined with density functional
theory (DFT) and compared with data from 1H-NMR
1D and 2D spectroscopy. This indicates the presence of
multiple conformations of an adduct with d(GpG), but only
one form of the adduct with d(TGGT). The importance of
a suitable theoretical model, and in particular basis set, in
reproducing experimental data is demonstrated. The DFT
theoretical model was extended to platinated base pair step
(GG/CC), allowing a comparison to the related compounds
cisplatin and oxaliplatin. Adducts of kiteplatin with larger
fragments of double-stranded DNA, including tetramer,
octamer, and dodecamer, were studied theoretically using
hybrid quantum mechanics/molecular mechanics methods.
Structural parameters of all the base-paired models were
evaluated and binding energies calculated in gas phase and in solution; these are compared across the series and
also with the related complexes cisplatin and oxaliplatin,
thus revealing insights into how kiteplatin binds to DNA
and similarities and differences between this and related
compounds
Temperament und Mutter-Kind-Interaktion im Säuglingsalter:Geschwistereinfluss und Geburtenrang
No full textDiese prospektive Längsschnittstudie untersucht bei (n=39) Säuglingen im Alter von 6 und 12 Monaten den Zusammenhang des Temperaments und der Mutter-Kind-Interaktion, den Einfluss des Geburtenrangs und mögliche Unterschiede zwischen Kindern mit (n=17) und ohne (n=22) Geschwister. Die Beurteilung des Temperaments erfolgt über den Infant Temperament Questionaire (ITQ) nach Carey, die Analyse der Mutter-Kind-Interaktion über das Manual Parent- Child Relational Assessment (PCERA) nach R. Clark. Die analysierte Interaktion zwischen Mutter und Kind zeigt nur eine geringe Abhängigkeit vom Temperament des Kindes. Die Annahme einer guten Passung i. S. von goodness of fit dient als Erklärung für das Resultat. Das Temperament ist nahezu unabhängig vom Geburtenrang, lediglich im Alter von einem Jahr zeigen die zweiten Kinder eine höheres Aktivitätsniveau und Kommunikationsvermögen. Die Interaktion der Mütter mit zwei Kindern erweist sich als signifikant positiver
Temperament und Mutter-Kind-Interaktion im Säuglingsalter:Geschwistereinfluss und Geburtenrang
No full textDiese prospektive Längsschnittstudie untersucht bei (n=39) Säuglingen im Alter von 6 und 12 Monaten den Zusammenhang des Temperaments und der Mutter-Kind-Interaktion, den Einfluss des Geburtenrangs und mögliche Unterschiede zwischen Kindern mit (n=17) und ohne (n=22) Geschwister. Die Beurteilung des Temperaments erfolgt über den Infant Temperament Questionaire (ITQ) nach Carey, die Analyse der Mutter-Kind-Interaktion über das Manual Parent- Child Relational Assessment (PCERA) nach R. Clark. Die analysierte Interaktion zwischen Mutter und Kind zeigt nur eine geringe Abhängigkeit vom Temperament des Kindes. Die Annahme einer guten Passung i. S. von goodness of fit dient als Erklärung für das Resultat. Das Temperament ist nahezu unabhängig vom Geburtenrang, lediglich im Alter von einem Jahr zeigen die zweiten Kinder eine höheres Aktivitätsniveau und Kommunikationsvermögen. Die Interaktion der Mütter mit zwei Kindern erweist sich als signifikant positiver
Waveform inversion of the S reflector west of Spain: fine structure of a detachment fault.
No full textThe S reflection west of Iberia has been interpreted as a low-angle detachment fault separating crustal fault blocks from partially serpentinized mantle. We apply full waveform inversion to investigate the fine structure of S. Our results confirm that S is largely a step increase in velocity (and density), probably from crustal rocks to partially serpentinized mantle peridotites. A ~50 m thick low velocity zone above S might represent a main fault zone of highly serpentinized peridotites or hydrofractured and altered crustal rocks above the main fault zone. Both interpretations imply focused fluid flow along S, raising the possibility that low-angle movement along S was aided by the development of local, transient high fluid pressures
CD8-positive T lymphocytes specific for murine cytomegalovirus immediate-early antigens mediate protective immunity
No full textWe have shown in a murine model system for acute, lethal cytomegalovirus (CMV) disease in the immunocompromised natural host that control of virus multiplication in tissues, protection from virus-caused tissue destruction, and survival are mediated by virus-specific CD8+ CD4-T lymphocytes. Protection from a lethal course of disease did not result in a rapid establishment of virus latency, but led to a long-lasting, persistent state of infection. The CD8- CD4+ subset of T lymphocytes was not effective by itself in controlling murine CMV (MCMV) multiplication in tissue or essential for the protective function of the CD8+ CD4- effector cells. The antiviral efficacy of the purified CD8+ CD4- subset was not impaired by preincubation with fibroblasts that presented viral structural antigens, but was significantly reduced after depletion of effector cells specific for the nonstructural immediate-early antigens of MCMV, which are specified by the first among a multitude of viral genes expressed during MCMV replication in permissive cells. Thus, MCMV disease provides the first example of a role for nonstructural herpesvirus immediate-early antigens in protective immunity
Rescue of myeloid lineage-committed preprogenitor cells from cytomegalovirus-infected bone marrow stroma
No full textThe effect of murine cytomegalovirus on myelopoiesis was studied in long-term bone marrow culture to find an in vitro correlate for the lethal virus interference with bone marrow reconstitution (W. Mutter, M. J. Reddehase, F. W. Busch, H.-J. Bühring, and U. H. Koszinowski, J. Exp. Med. 167:1645-1658, 1988). The in vitro generation of granulocyte-monocyte progenitors (CFU-GM) discontinued after infection of the stromal cell layer, whereas the proliferation and differentiation of CFU-GM to granulocyte-monocyte colonies remained unaffected. A protocol was established to probe the functional integrity of earlier hematopoietic cells. Pre-CFU-GM (the progenitors of the CFU-GM) could be recovered from an infected bone marrow donor culture by transfer onto an inductive recipient stromal cell layer. Thus, at least in vitro, infection of bone marrow stroma appears to be the only cause of the defect in myelopoiesis
Verhaltensauffälligkeiten von Kindern krebskranker Mütter: Empirische Ergebnisse aus der onkologischen Mutter-Kind-Rehabilitation
No full textZusammenfassung
Gegenstand: Ziel der Studie war es, Verhaltensauffälligkeiten von Kindern krebskranker Mütter, die an einer onkologischen Mutter-Kind-Rehabilitation teilgenommen hatten, zu erheben. Material und Methoden:159 Mütter mit einer Krebserkrankung berichteten mittels eines Katamnese-Fragebogen von Verhaltensänderungen ihrer Kinder. Außerdem wurden die Lebensqualität (SF-12) und psychopathologische Symptome (BSI) der Mütter sowie soziodemografische Parameter erhoben. Ergebnisse: In den Einschätzungen zu 234 Kindern wurden vor allem „starke Anhänglichkeit“ berichtet, gefolgt von „Angst vor Trennung“ und der „Angst, die Mutter könnte sterben“. Unterschiede in den erlebten Auffälligkeiten des Kindes waren nicht mit dem Geschlecht des Kindes verbunden, wohl aber mit einem höheren Kindesalter. Die eigene Lebensqualität sowie Depressions-, Ängstlichkeits-und Somatisierungswerte der Mütter korrelierten signifikant mit den erlebten Verhaltensauffälligkeiten beim Kind. Schlussfolgerung: Onkologisch erkrankte Mütter nehmen bei ihren Kindern häufig Verhaltensauffälligkeiten wahr. Daher sollte in der onkologischen Mutter-Kind-Rehabilitation routinemäßig eine psychosoziale Diagnostik und Betreuung der Kinder erfolgen.</jats:p
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