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101.
Lovorka Grgurevic Boris Macek Mladen Mercep Mislav Jelic Tomislav Smoljanovic Igor Erjavec Ivo Dumic-Cule Stefan Prgomet Dragan Durdevic Drazen Vnuk Marija Lipar Marko Stejskal Vera Kufner Jelena Brkljacic Drazen Maticic Slobodan Vukicevic 《Biochemical and biophysical research communications》2011,(1):80
Members of the astacin family of metalloproteinases such as human bone morphogenetic protein 1 (BMP-1) regulate morphogenesis by processing precursors to mature functional extracellular matrix (ECM) proteins and several growth factors including TGFβ, BMP2, BMP4 and GFD8. We have recently discovered that BMP1-3 isoform of the Bmp-1 gene circulates in the human plasma and is significantly increased in patients with acute bone fracture. We hypothesized that circulating BMP1-3 might have an important role in bone repair and serve as a novel bone biomarker. When administered systemically to rats with a long bone fracture and locally to rabbits with a critical size defect of the ulna, recombinant human BMP1-3 enhanced bone healing. In contrast, neutralization of the endogenous BMP1-3 by a specific polyclonal antibody delayed the bone union. Invitro BMP1-3 increased the expression of collagen type I and osteocalcin in MC3T3-E1 osteoblast like cells, and enhanced the formation of mineralized bone nodules from bone marrow mesenchymal stem cells. We suggest that BMP1-3 is a novel systemic regulator of bone repair. 相似文献
102.
Wållberg H Löfdahl PK Tschapalda K Uhlén M Tolmachev V Nygren PK Ståhl S 《Protein expression and purification》2011,76(1):127-135
Affibody molecules generated by combinatorial protein engineering to bind the human epidermal growth factor receptor 2 (HER2) have in earlier studies proven to be promising tracers for HER2-mediated molecular imaging of cancer. Amino acid extensions either at the N- or C-terminus of these Z(HER2) affibody molecules, have been successfully employed for site-specific radiolabeling of the tracer candidates. Hexahistidyls or other tags, which would be convenient for recovery purposes, should be avoided since they could negatively influence the tumor targeting efficacy and biodistribution properties of the tracer. Using a new ?-lactamase-based protein fragment complementation assay (PCA), an affibody molecule was isolated which bound a Z(HER2) affibody molecule with sub-micromolar affinity, but not unrelated affibody molecules. This suggests that the interacting area include the HER2-binding surface of Z(HER2). This novel anti-idiotypic affibody molecule Z(E01) was produced in Escherichia coli, purified, and chemically coupled to a chromatography resin in order to generate an affibody-based affinity column, suitable for recovery of different variants of Z(HER2) affibody molecules, having a common binding surface for HER2. Eight such Z(HER2) affibody molecules, designed for future radioimaging investigations, having different C-terminal peptide extensions aimed for radioisotope ((??m)Tc)-chelation, were successfully produced and recovered in a single step to high purity using the anti-idiotypic affibody ligand for the affinity purification. These results clearly suggest a potential for the development of anti-idiotypic affibody-based resins for efficient recovery of related variants of a target protein that might have altered biochemical properties, thus avoiding the cumbersome design of specific recovery schemes for each variant of a target protein. 相似文献
103.
Neus Mestre-Farrs Santiago Guerrero Nadine Bley Ezequiel Rivero Olga Coll Eva Borrs Eduard Sabid Alberto Indacochea Carlos Casillas-Serra Aino
I Jrvelin Baldomero Oliva Alfredo Castello Stefan Hüttelmaier Ftima Gebauer 《Nucleic acids research》2022,50(14):8207
RNA-binding proteins (RBPs) have been relatively overlooked in cancer research despite their contribution to virtually every cancer hallmark. Here, we use RNA interactome capture (RIC) to characterize the melanoma RBPome and uncover novel RBPs involved in melanoma progression. Comparison of RIC profiles of a non-tumoral versus a metastatic cell line revealed prevalent changes in RNA-binding capacities that were not associated with changes in RBP levels. Extensive functional validation of a selected group of 24 RBPs using five different in vitro assays unveiled unanticipated roles of RBPs in melanoma malignancy. As proof-of-principle we focused on PDIA6, an ER-lumen chaperone that displayed a novel RNA-binding activity. We show that PDIA6 is involved in metastatic progression, map its RNA-binding domain, and find that RNA binding is required for PDIA6 tumorigenic properties. These results exemplify how RIC technologies can be harnessed to uncover novel vulnerabilities of cancer cells. 相似文献
104.
Shiraz Badurdeen Peter G. Davis Stuart B. Hooper Susan Donath Georgia A. Santomartino Alissa Heng Diana Zannino Monsurul Hoq C. Omar F Kamlin Stefan C. Kane Anthony Woodward Calum T. Roberts Graeme R. Polglase Douglas A. Blank 《PLoS medicine》2022,19(6)
BackgroundGlobally, the majority of newborns requiring resuscitation at birth are full term or late-preterm infants. These infants typically have their umbilical cord clamped early (ECC) before moving to a resuscitation platform, losing the potential support of the placental circulation. Physiologically based cord clamping (PBCC) is clamping the umbilical cord after establishing lung aeration and holds promise as a readily available means of improving early newborn outcomes. In mechanically ventilated lambs, PBCC improved cardiovascular stability and reduced hypoxia. We hypothesised that PBCC compared to ECC would result in higher heart rate (HR) in infants needing resuscitation, without compromising safety.Methods and findingsBetween 4 July 2018 and 18 May 2021, infants born at ≥32+0 weeks’ gestation with a paediatrician called to attend were enrolled in a parallel-arm randomised trial at 2 Australian perinatal centres. Following initial stimulation, infants requiring further resuscitation were randomised within 60 seconds of birth using a smartphone-accessible web link. The intervention (PBCC) was to establish lung aeration, either via positive pressure ventilation (PPV) or effective spontaneous breathing, prior to cord clamping. The comparator was early cord clamping (ECC) prior to resuscitation. The primary outcome was mean HR between 60 to 120 seconds after birth, measured using 3-lead electrocardiogram, extracted from video recordings blinded to group allocation. Nonrandomised infants had deferred cord clamping (DCC) ≥120 seconds in the observational study arm.Among 508 at-risk infants enrolled, 123 were randomised (n = 63 to PBCC, n = 60 to ECC). Median (interquartile range, IQR) for gestational age was 39.9 (38.3 to 40.7) weeks in PBCC infants and 39.6 (38.4 to 40.4) weeks in ECC infants. Approximately 49% and 50% of the PBCC and ECC infants were female, respectively. Five infants (PBCC = 2, ECC = 3, 4% total) had missing primary outcome data. Cord clamping occurred at a median (IQR) of 136 (126 to 150) seconds in the PBCC arm and 37 (27 to 51) seconds in the ECC arm. Mean HR between 60 to 120 seconds after birth was 154 bpm (beats per minute) for PBCC versus 158 bpm for ECC (adjusted mean difference −6 bpm, 95% confidence interval (CI) −17 to 5 bpm, P = 0.39). Among 31 secondary outcomes, postpartum haemorrhage ≥500 ml occurred in 34% and 32% of mothers in the PBCC and ECC arms, respectively. Two hundred ninety-five nonrandomised infants (55% female) with median (IQR) gestational age of 39.6 (38.6 to 40.6) weeks received DCC. Data from these infants was used to create percentile charts of expected HR and oxygen saturation in vigorous infants receiving DCC. The trial was limited by the small number of infants requiring prolonged or advanced resuscitation. PBCC may provide other important benefits we did not measure, including improved maternal–infant bonding and higher iron stores.ConclusionsIn this study, we observed that PBCC resulted in similar mean HR compared to infants receiving ECC. The findings suggest that for infants ≥32+0 weeks’ gestation who receive brief, effective resuscitation at closely monitored births, PBCC does not provide additional benefit over ECC (performed after initial drying and stimulation) in terms of key physiological markers of transition. PBCC was feasible using a simple, low-cost strategy at both cesarean and vaginal births. The percentile charts of HR and oxygen saturation may guide clinicians monitoring the transition of at-risk infants who receive DCC.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618000621213.Shiraz Badurdeen and colleagues evaluate whether physiologically-based cord clamping provides physiological benefits over early cord clamping for infants requiring resuscitation at birth. 相似文献
105.
Valter Bergant Shintaro Yamada Vincent Grass Yuta Tsukamoto Teresa Lavacca Karsten Krey MariaTeresa Mühlhofer Sabine Wittmann Armin Ensser Alexandra Herrmann Anja vom Hemdt Yuriko Tomita Shutoku Matsuyama Takatsugu Hirokawa Yiqi Huang Antonio Piras Constanze A Jakwerth Madlen Oelsner Susanne Thieme Alexander Graf Stefan Krebs Helmut Blum Beate M Kümmerer Alexey Stukalov Carsten B SchmidtWeber Manabu Igarashi Thomas Gramberg Andreas Pichlmair Hiroki Kato 《The EMBO journal》2022,41(17)
The SARS‐CoV‐2 infection cycle is a multistage process that relies on functional interactions between the host and the pathogen. Here, we repurposed antiviral drugs against both viral and host enzymes to pharmaceutically block methylation of the viral RNA 2''‐O‐ribose cap needed for viral immune escape. We find that the host cap 2''‐O‐ribose methyltransferase MTr1 can compensate for loss of viral NSP16 methyltransferase in facilitating virus replication. Concomitant inhibition of MTr1 and NSP16 efficiently suppresses SARS‐CoV‐2 replication. Using in silico target‐based drug screening, we identify a bispecific MTr1/NSP16 inhibitor with anti‐SARS‐CoV‐2 activity in vitro and in vivo but with unfavorable side effects. We further show antiviral activity of inhibitors that target independent stages of the host SAM cycle providing the methyltransferase co‐substrate. In particular, the adenosylhomocysteinase (AHCY) inhibitor DZNep is antiviral in in vitro, in ex vivo, and in a mouse infection model and synergizes with existing COVID‐19 treatments. Moreover, DZNep exhibits a strong immunomodulatory effect curbing infection‐induced hyperinflammation and reduces lung fibrosis markers ex vivo. Thus, multispecific and metabolic MTase inhibitors constitute yet unexplored treatment options against COVID‐19. 相似文献
106.
Stefan Vogel 《Plant Systematics and Evolution》1955,102(4-5):486-500
Ohne Zusammenfassung 相似文献
107.
Marcus Bär Joachim Klaer Lothar Weinhardt Regan G. Wilks Stefan Krause Monika Blum Wanli Yang Clemens Heske Hans‐Werner Schock 《Liver Transplantation》2013,3(6):777-781
The surface properties of CuInS2 (CIS) thin‐film solar cell absorbers are investigated by a combination of electron and soft X‐ray spectroscopies. Spatially separated regions of varying colors are observed and identified to be dominated by either CuS or Cu2S surface phases. After their removal by KCN etching, the samples cannot be distinguished by eye and the CIS surface is found to be Cu‐deficient in both regions. However, a significantly more pronounced off‐stoichiometry in the region initially covered by Cu2S can be identified. In this region, the resulting surface band gap is also significantly larger than the EgSurf of the initially CuS‐terminated region. Such variations may represent a hidden parameter which, if overlooked, induces irreproducibility and thus prevents systematic optimization efforts. 相似文献
108.
Longitudinal Phenotypic Analysis of Human Immunodeficiency Virus Type 1-Specific Cytotoxic T Lymphocytes: Correlation with Disease Progression 下载免费PDF全文
Graham S. Ogg Stefan Kostense Michel R. Klein Suzanne Jurriaans Drte Hamann Andrew J. McMichael Frank Miedema 《Journal of virology》1999,73(11):9153-9160
Few studies have examined longitudinal changes in human immunodeficiency virus type 1 (HIV)-specific cytotoxic T lymphocytes (CTL). To more closely define the natural history of HIV-specific CTL, we used HLA-peptide tetrameric complexes to study the longitudinal CD8(+) T-cell response evolution in 16 A*0201-positive untreated individuals followed clinically for up to 14 years. As early as 1 to 2 years after seroconversion, we found a significant association between high frequencies of A*0201-restricted p17(Gag/Pol) tetramer-binding cells and slower disease progression (P < 0.01). We observed that responses could remain stable over many months, but any longitudinal changes that occurred were typically accompanied by reciprocal changes in RNA viral load. Phenotypic analysis with markers CD45RO, CD45RA, and CD27 identified distinct subsets of antigen-specific cells and the preferential loss of CD27(+) CD45RO(+) cells during periods of rapid decline in the frequency of tetramer-binding cells. In addition we were unable to confirm previous studies showing a consistent selective loss of HIV-specific cells in the context of sustained Epstein-Barr virus-specific cell frequencies. Overall, these data support a role of HIV-specific CTL in the control of disease progression and suggest that the ultimate loss of such CTL may be preferentially from the CD27(+) CD45RO(+) subset. 相似文献
109.
Vera Holland Stefan Koller Stefan Lukas Wolfgang Brüggemann 《Trees - Structure and Function》2016,30(1):215-226
Key message
Different environmental conditions affect tree senescence by different patterns of carbohydrate concentrations and have specific impact on the dissection of the photosynthetic apparatus.Abstract
A proactive cultivation of Mediterranean broadleaf species, including oaks, has been suggested to fill possible temporal and spatial gaps in forestry created by Climate Change in Central Europe in the future. Climate can affect trees in several different ways, e.g., by modulating the course of leaf senescence. Senescence-associated processes, like regulation of carbohydrates and changes in chlorophyll fluorescence under drought stress conditions were studied with leaf tissue of drought-tolerant downy oak (Quercus pubescens). Two months of consistent drought stress in a frost-free greenhouse led to significantly earlier senescence and significant increased amounts of soluble sugars in the leaves of the drought-stressed group in comparison to a well-watered control group. Similar sugar accumulation was observed in trees outdoors, after exposure to frost. In contrast to monocarpic plants the accumulation of free sugars is neither triggering leaf senescence, nor is it a side effect of age-depending changes in Q. pubescens. Instead, sugar accumulation is induced by abiotical factors, like drought and frost. Furthermore, we suggest that the senescence process in the absence of drought stress or frost depends on the source status of the leaf, which, in term, is a function of light (through photosynthesis) and night temperature (through respiration). Contents of the storage metabolite starch decreased during late summer in all three groups. Drought-stressed plants showed a decline of the connectivity of photosystem II antenna, reflected as the L-band in the chlorophyll fluorescence induction curves, and stronger correlations between the declines in the capacity of photosynthetic dark reactions and electron transport-associated chlorophyll fluorescence parameters. We conclude that the disassembly of single parts of the photosynthetic apparatus during leaf senescence is a uniform process, but the onset of this process depends on abiotical environmental factors.110.
Winda Ika Susanti Tamara Bartels Valentyna Krashevska Rahayu Widyastuti Louis Deharveng Stefan Scheu Anton Potapov 《Ecology and evolution》2021,11(15):10686
Rainforest conversion and expansion of plantations in tropical regions are associated with changes in animal communities and biodiversity decline. In soil, Collembola are one of the most numerous invertebrate groups that affect the functioning of microbial communities and support arthropod predators. Despite that, information on the impact of changes in land use in the tropics on species and trait composition of Collembola communities is very limited. We investigated the response of Collembola to the conversion of rainforest into rubber agroforestry (“jungle rubber”), rubber, and oil palm plantations in Jambi Province (Sumatra, Indonesia), a region which experienced one of the strongest recent deforestation globally. Collembola were sampled in 2013 and 2016 from the litter and soil layer using heat extraction, and environmental factors were measured (litter C/N ratio, pH, water content, composition of microbial community and predator abundance). In the litter layer, density and species richness in plantation systems were 25%–38% and 30%–40% lower, respectively, than in rainforest. However, in the soil layer, density, species richness, and trait diversity of Collembola were only slightly affected by land‐use change, contrasting the response of many other animal groups. Species and trait composition of Collembola communities in litter and soil differed between each of the land‐use systems. Water content and pH were identified as main factors related to the differences in species and trait composition in both litter and soil, followed by the density of micro‐ and macropredators. Dominant species of Collembola in rainforest and jungle rubber were characterized by small body size, absence of furca, and absence of intense pigmentation, while in plantations, larger species with long furca and diffuse or patterned pigmentation were more abundant. Overall, land‐use change negatively affected Collembola communities in the litter layer, but its impact was lower in the soil layer. Several pantropical genera of Collembola (i.e., Isotomiella, Pseudosinella, and Folsomides) dominated across land‐use systems, reflecting their high environmental adaptability and/or efficient dispersal, calling for studies on their ecology and genetic diversity. The decline in species richness and density of litter‐dwelling Collembola with the conversion of rainforest into plantation systems calls for management practices mitigating negative effects of the deterioration of the litter layer in rubber plantations, but even more in oil palm plantations. 相似文献