Infection of cells with replication deficient adenovirus induces cell cycle alterations and leads to downregulation of E2F-1

AbstractGene products of recombinant replication-deficient adenovirus vectors of the first generation (Ad vector) can induce cell cycle dysregulation and apoptosis after infection in eukaryotic cells. The mechanisms underlying this complex process are largely unknown. Therefore, we investigated the regulation of the pRb/E2F-1 complex, which controls transition from G0/G1 to S phase of the cell cycle. As Ad vector infection results in a decrease in the number of cells in G0/G1 phase of the cell cycle, we observed a decline of the pRb protein level and, surprisingly, also a decrease of the E2F-1 protein and mRNA level in infected cell lines. Furthermore, in contrast to the reduction of cells in the G0/G1 phase we observed increased protein levels of p53 and p21 proteins. However, as experiments in p53 deficient cell lines indicated, the decrease of pRb and E2F-1 is independent of p53 and p21 expression. Moreover, results obtained with Rb deficient cell lines indicated that the reduced E2F-1 expression is independent of pRb. These results suggest that Ad vector-induced cell cycle dysregulation is associated with a specific downregulation of E2F-1 independent of Rb and p53 genomic status of cells

Considerations for determining optimal mouse caging density

At the 2006 National Meeting of the American Association of Laboratory Animal Science, a panel discussed the question of what constitutes optimal or acceptable housing density for mice. Though there is a consensus that present guidelines are somewhat arbitrarily defined, scientific research has not yet been able to provide clear recommendations for amending them. Speakers explored the many factors that influence decisions on mouse housing, including regulatory requirements, scientific data and their interpretation, financial considerations and ethical concerns. The panel largely agreed that animal well-being should be the measure of interest in evaluating housing density and that well-being includes not only physical health, but also animals\u27 behavior, productivity and preference

Weak short-term survival of radio-tagged Pin-tailed Sangrouse (Pterocles alchata) in France raises questions about capture and attached transmitters

Un des outils à la disposition des biologistes de la conservation pour étudier comment les espèces utilisent les habitats, thème central en écologie des populations, est la radio-télémétrie. Cette technique impose la capture et la pose d’émetteurs radio. Ces actions peuvent avoir un effet préjudiciable sur les oiseaux mais dans le cadre d’espèces difficiles à détecter, la méthode reste la seule pour acquérir des informations précises. Nous examinons ici le bilan d’un test de suivi radio-télémétrique sur le Ganga cata (Pterocles alchata) en France. Il en ressort que le taux de mortalité à court terme est très élevé. Aucune des informations collectées ne permet de l’expliquer clairement. Ces résultats sont comparés et discutés avec ceux obtenus en Espagne sur cette espèce.Radio-telemetry is widely used by conservation biologists for collecting data on habitat use by animal species, a central topic in population ecology. For this purpose, the capture of individuals and attachment of transmitters on animals are necessary. Those actions might have a harmful effect on birds but when species are difficult to detect it remains the only method available. We report results of a radio-telemetry study on Pin-tailed Sandgrouse (Pterocles alchata) in France. Although the capture and attachment of transmitters are possible, short-term mortality is very high. Collected data do not explain such a rate. We compare those results to a recent study on the same species in Spain and to a meta-analysis on birds

Oriented attachment explains cobalt ferrite nanoparticle growth in bioinspired syntheses

Oriented attachment has created a great debate about the description of crystal growth throughout the last decade. This aggregationbased model has successfully described biomineralization processes as well as forms of inorganic crystal growth, which could not be explained by classical crystal growth theory. Understanding the nanoparticle growth is essential since physical properties, such as the magnetic behavior, are highly dependent on the microstructure, morphology and composition of the inorganic crystals. In this work, the underlying nanoparticle growth of cobalt ferrite nanoparticles in a bioinspired synthesis was studied. Bioinspired syntheses have sparked great interest in recent years due to their ability to influence and alter inorganic crystal growth and therefore tailor properties of nanoparticles. In this synthesis, a short synthetic version of the protein MMS6, involved in nanoparticle formation within magnetotactic bacteria, was used to alter the growth of cobalt ferrite. We demonstrate that the bioinspired nanoparticle growth can be described by the oriented attachment model. The intermediate stages proposed in the theoretical model, including primary-building-block-like substructures as well as mesocrystal-like structures, were observed in HRTEM measurements. These structures display regions of substantial orientation and possess the same shape and size as the resulting discs. An increase in orientation with time was observed in electron diffraction measurements. The change of particle diameter with time agrees with the recently proposed kinetic model for oriented attachmen

Determination of the emission rates of CO2 point sources with airborne lidar

We report on CO2 emissions of a coal-fired power plant derived from flight measurements performed with the IPDA lidar CHARM-F during the CoMet campaign in spring 2018. Despite the results being in broad agreement with reported emissions, we observe strong variations between successive flyovers. Using a high-resolution large eddy simulation, we identify strong atmospheric turbulence as the cause for the variations and recommend more favorable measurement conditions for future campaign planning

Long-Term Relapse-Free Survival by Interdisciplinary Collaboration in a Patient with Metastatic Pancreatic Cancer (UICC IV)

Introduction: The prognostic outlook for patients suffering from pancreatic cancer is generally poor. Particularly in cases of advanced and metastatic disease, long-term relapse-free survival may be achieved only in a few cases. Case Report: A 45-year-old patient presented with metastatic pancreatic cancer. Liver metastases had been intra-operatively confirmed by histology. Prior to initiating treatment, a portacath was surgically implanted. Subsequently, the patient received a weekly dose of 1,000 mg/m2 gemcitabine combined with 2,000 mg/m2 high-dose 5-fluorouracil as a 24-hour infusion for palliative treatment. As the patient was suffering from a stenosis of the ductus hepaticus communis, an endoprosthesis was primarily implanted. After 18 applications of chemotherapy during which only low toxic side effects such as nausea, vomiting and alopecia (NCI-CTC grade 1) presented, a partial remission of the primary tumor was observed. In the course of chemotherapy treatment, the carbohydrate antigen 19-9 tumor marker value normalized. Thus, the interdisciplinary tumor board of the University of Erlangen decided to perform a laparoscopy to evaluate the status of liver metastases after palliative chemotherapy treatment. Subsequently, the primary tumor could be completely resected (pT2, pN0, pM0, L0, V0, G2, R0); liver metastases were not observed. Eight years after the initial diagnosis, the patient is relapse-free, professionally fully integrated and presents with an excellent performance status. Conclusion: Patients suffering from metastatic pancreatic cancer may benefit from treatment combinations with palliative intent. In singular cases, patients may even have a curative treatment option, provided a close interdisciplinary collaboration exists

A suicide gene approach using the human pro-apoptotic protein tBid inhibits HIV-1 replication

<p>Abstract</p> <p>Background</p> <p>Regulated expression of suicide genes is a powerful tool to eliminate specific subsets of cells and will find widespread usage in both basic and applied science. A promising example is the specific elimination of human immunodeficiency virus type 1 (HIV-1) infected cells by LTR-driven suicide genes. The success of this approach, however, depends on a fast and effective suicide gene, which is expressed exclusively in HIV-1 infected cells. These preconditions have not yet been completely fulfilled and, thus, success of suicide approaches has been limited so far. We tested truncated Bid (tBid), a human pro-apoptotic protein that induces apoptosis very rapidly and efficiently, as suicide gene for gene therapy against HIV-1 infection.</p> <p>Results</p> <p>When tBid was introduced into the HIV-1 LTR-based, Tat- and Rev-dependent transgene expression vector pLRed(INS)₂R, very efficient induction of apoptosis was observed within 24 hours, but only in the presence of both HIV-1 regulatory proteins Tat and Rev. Induction of apoptosis was not observed in their absence. Cells containing this vector rapidly died when transfected with plasmids containing full-length viral genomic DNA, completely eliminating the chance for HIV-1 replication. Viral replication was also strongly reduced when cells were infected with HIV-1 particles.</p> <p>Conclusions</p> <p>This suicide vector has the potential to establish a safe and effective gene therapy approach to exclusively eliminate HIV-1 infected cells before infectious virus particles are released.</p

Multi-walled carbon nanotube physicochemical properties predict pulmonary inflammation and genotoxicity

<p>Lung deposition of multi-walled carbon nanotubes (MWCNT) induces pulmonary toxicity. Commercial MWCNT vary greatly in physicochemical properties and consequently in biological effects. To identify determinants of MWCNT-induced toxicity, we analyzed the effects of pulmonary exposure to 10 commercial MWCNT (supplied in three groups of different dimensions, with one pristine and two/three surface modified in each group). We characterized morphology, chemical composition, surface area and functionalization levels. MWCNT were deposited in lungs of female C57BL/6J mice by intratracheal instillation of 0, 6, 18 or 54 μg/mouse. Pulmonary inflammation (neutrophil influx in bronchoalveolar lavage (BAL)) and genotoxicity were determined on day 1, 28 or 92. Histopathology of the lungs was performed on day 28 and 92. All MWCNT induced similar histological changes. Lymphocytic aggregates were detected for all MWCNT on day 28 and 92. Using adjusted, multiple regression analyses, inflammation and genotoxicity were related to dose, time and physicochemical properties. The specific surface area (BET) was identified as a positive predictor of pulmonary inflammation on all post-exposure days. In addition, length significantly predicted pulmonary inflammation, whereas surface oxidation (–OH and –COOH) was predictor of lowered inflammation on day 28. BET surface area, and therefore diameter, significantly predicted genotoxicity in BAL fluid cells and lung tissue such that lower BET surface area or correspondingly larger diameter was associated with increased genotoxicity. This study provides information on possible toxicity-driving physicochemical properties of MWCNT. The results may contribute to safe-by-design manufacturing of MWCNT, thereby minimizing adverse effects.</p

Fast Bound Pool Fraction Mapping Using Stimulated Echoes

Magnetization transfer imaging advanced to an indispensible tool for investigating white matter changes. Quantitative magnetization transfer imaging methods allow the determination of the bound pool fraction (BPF), which is thought to be directly linked to myelin integrity. Long acquisition times and high specific absorption rates are still inhibiting broad in vivo utilization of currently available BPF mapping techniques. Herewith, a stimulated echoes amplitude modulation-based, single-shot echo planar imaging technique for BPF and T1 quantification is presented at 3T. It allows whole brain mapping in 10–15 min and is low in specific absorption rates. The method was validated with different concentrations of bovine serum albumin (BSA) phantoms. Intra- and inter-subject variability was assessed in vivo. Phantom measurements verified linearity between bovine serum albumin concentrations and measured BPF, which was independent of T1 variations. T1 values in the phantoms correlated well with values provided by standard T1 mapping methods. Intrasubject variability was minimal and mean regional BPFs of 10 volunteers (e.g., left frontal white matter = 0.135 ± 0.003, right frontal white matter = 0.129 ± 0.006) were in line with previously published data. Assessment of interhemispheric BPF differences revealed significantly higher BPF for the left brain hemisphere. To sum up, these results suggest the proposed method useful for cross-sectional and longitudinal studies of white matter changes in the human brain. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc