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      • Angular dependence of photoemission time delay in helium

        Heuser, Sebastian,Jimé,nez Galá,n, Á,lvaro,Cirelli, Claudio,Marante, Carlos,Sabbar, Mazyar,Boge, Robert,Lucchini, Matteo,Gallmann, Lukas,Ivanov, Igor,Kheifets, Anatoli S.,Dahlstr&oum American Physical Society 2016 Physical Review A Vol.94 No.6

        <P>Time delays of electrons emitted from an isotropic initial state with the absorption of a single photon and leaving behind an isotropic ion are angle independent. Using an interferometric method involving XUV attosecond pulse trains and an IR-probe field in combination with a detection scheme, which allows for full three-dimensional momentum resolution, we show that measured time delays between electrons liberated from the 1s(2) spherically symmetric ground state of helium depend on the emission direction of the electrons relative to the common linear polarization axis of the ionizing XUV light and the IR-probing field. Such time delay anisotropy, for which we measure values as large as 60 as, is caused by the interplay between final quantum states with different symmetry and arises naturally whenever the photoionization process involves the exchange of more than one photon. With the support of accurate theoretical models, the angular dependence of the time delay is attributed to small phase differences that are induced in the laser-driven continuum transitions to the final states. Since most measurement techniques tracing attosecond electron dynamics involve the exchange of at least two photons, this is a general and significant effect that must be taken into account in all measurements of time delays involving photoionization processes.</P>

      • KCI등재

        Genotoxic Evaluation of Mikania laevigata Extract on DNA Damage Caused by Acute Coal Dust Exposure

        Freitas, Tiago P.,Heuser, Vanina D.,Tavares, Priscila,Leffa, Daniela D.,Silva, Gabriela A. da,Citadini-Zanette, Vanilde,Romao, Pedro R.T.,Pinho, Ricardo A.,Streck, Emilio L.,Andrade, Vanessa M. The Korean Society of Food Science and Nutrition 2009 Journal of medicinal food Vol.12 No.3

        In the present article, we report data on the possible antigenotoxic activity of Mikania laevigata extract (MLE) after acute intratracheal instillation of coal dust using the comet assay in peripheral blood, bone marrow, and liver cells and the micronucleus test in peripheral blood of Wistar rats. The animals were pretreated for 2 weeks with saline solution (groups 1 and 2) or MLE (100 mg/kg) (groups 3 and 4). On day 15, the animals were anesthetized with ketamine (80 mg/kg) and xylazine (20 mg/kg), and gross mineral coal dust (3 mg/0.3mL saline) (groups 2 and 4) or saline solution (0.3 mL) (groups 1 and 3) was administered directly in the lung by intratracheal administration. Fifteen days after coal dust or saline instillation, the animals were sacrificed, and the femur, liver, and peripheral blood were removed. The results showed a general increase in the DNA damage values at 8 hours for all treatment groups, probably related to surgical procedures that had stressed the animals. Also, liver cells from rats treated with coal dust, pretreated or not with MLE, showed statistically higher comet assay values compared to the control group at 14 days after exposure. These results could be expected because the liver metabolizes a variety of organic compounds to more polar by-products. On the other hand, the micronucleus assay results did not show significant differences among groups. Therefore, our data do not support the antimutagenic activity of M. laevigata as a modulator of DNA damage after acute coal dust instillation.

      • Eisosome Ultrastructure and Evolution in Fungi, Microalgae, and Lichens

        Lee, Jae-Hyeok,Heuser, John E.,Roth, Robyn,Goodenough, Ursula American Society for Microbiology 2015 EUKARYOTIC CELL Vol.14 No.10

        <P>Eisosomes are among the few remaining eukaryotic cellular differentations that lack a defined function(s). These trough-shaped invaginations of the plasma membrane have largely been studied in <I>Saccharomyces cerevisiae</I>, in which their associated proteins, including two BAR domain proteins, have been identified, and homologues have been found throughout the fungal radiation. Using quick-freeze deep-etch electron microscopy to generate high-resolution replicas of membrane fracture faces without the use of chemical fixation, we report that eisosomes are also present in a subset of red and green microalgae as well as in the cysts of the ciliate <I>Euplotes</I>. Eisosome assembly is closely correlated with both the presence and the nature of cell walls. Microalgal eisosomes vary extensively in topology and internal organization. Unlike fungi, their convex fracture faces can carry lineage-specific arrays of intramembranous particles, and their concave fracture faces usually display fine striations, also seen in fungi, that are pitched at lineage-specific angles and, in some cases, adopt a broad-banded patterning. The conserved genes that encode fungal eisosome-associated proteins are not found in sequenced algal genomes, but we identified genes encoding two algal lineage-specific families of predicted BAR domain proteins, called Green-BAR and Red-BAR, that are candidate eisosome organizers. We propose a model for eisosome formation wherein (i) positively charged recognition patches first establish contact with target membrane regions and (ii) a (partial) unwinding of the coiled-coil conformation of the BAR domains then allows interactions between the hydrophobic faces of their amphipathic helices and the lipid phase of the inner membrane leaflet, generating the striated patterns.</P>

      • KCI등재

        Genotoxic Evaluation of Mikania laevigata Extract on DNA Damage Caused by Acute Coal Dust Exposure

        Tiago P. Freitas,Vanina D. Heuser,Priscila Tavares,Daniela D. Leffa,Gabriela A. da Silva,Vanilde Citadini-Zanette,Pedro R.T. Romão,Ricardo A. Pinho,Emilio L. Streck,Vanessa M. Andrade 한국식품영양과학회 2009 Journal of medicinal food Vol.12 No.3

        In the present article, we report data on the possible antigenotoxic activity of Mikania laevigata extract (MLE) after acute intratracheal instillation of coal dust using the comet assay in peripheral blood, bone marrow, and liver cells and the micronucleus test in peripheral blood of Wistar rats. The animals were pretreated for 2 weeks with saline solution (groups 1 and 2) or MLE (100mg/kg) (groups 3 and 4). On day 15, the animals were anesthetized with ketamine (80mg/kg) and xylazine (20mg/kg), and gross mineral coal dust (3mg/0.3mL saline) (groups 2 and 4) or saline solution (0.3mL) (groups 1 and 3) was administered directly in the lung by intratracheal administration. Fifteen days after coal dust or saline instillation, the animals were sacrificed, and the femur, liver, and peripheral blood were removed. The results showed a general increase in the DNA damage values at 8 hours for all treatment groups, probably related to surgical procedures that had stressed the animals. Also, liver cells from rats treated with coal dust, pretreated or not with MLE, showed statistically higher comet assay values compared to the control group at 14 days after exposure. These results could be expected because the liver metabolizes a variety of organic compounds to more polar by-products. On the other hand, the micronucleus assay results did not show significant differences among groups. Therefore, our data do not support the antimutagenic activity of M. laevigata as a modulator of DNA damage after acute coal dust instillation.

      • Utilization of PhotoinducedCharge-Separated Stateof Donor–Acceptor-Linked Molecules for Regulation of Cell MembranePotential and Ion Transport

        Numata, Tomohiro,Murakami, Tatsuya,Kawashima, Fumiaki,Morone, Nobuhiro,Heuser, John E.,Takano, Yuta,Ohkubo, Kei,Fukuzumi, Shunichi,Mori, Yasuo,Imahori, Hiroshi American Chemical Society 2012 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.134 No.14

        <P>The control of ion transport across cell membranes by light is an attractive strategy that allows targeted, fast control of precisely defined events in the biological membrane, Here we report a novel general strategy for the control of membrane potential and ion transport by using charge-separation molecules and light. Delivery of charge-separation molecules to the plasma membrane of PC12 cells by a membranous nanocarrier and subsequent light irradiation led to depolarization of the membrane potential as well as inhibition of the potassium ion flow across the membrane. Photoregulation of the cell membrane potential and ion transport by using charge-separation molecules is highly promising for control of cell functions.</P>

      • KCI등재

        Characterization of Expression and Function of the Formins FHOD1, INF2, and DAAM1 in HER2-Positive Breast Cancer

        Minna Peippo,Maria Gardberg,Pauliina Kronqvist,Olli Carpén,Vanina D. Heuser 한국유방암학회 2023 Journal of breast cancer Vol.26 No.6

        Purpose: Human epidermal growth factor receptor 2 (HER2)-targeted therapies, such as trastuzumab, benefit patients with HER2-positive metastatic breast cancer; however, owing to traditional pathway activation or alternative signaling, resistance persists. Given the crucial role of the formin family in shaping the actin cytoskeleton during cancer progression, these proteins may function downstream of the HER2 signaling pathway. Our aim was to uncover the potential correlations between formins and HER2 expression using a combination of public databases, immunohistochemistry, and functional in vitro assays. Methods: Using online databases, we identified a negative prognostic correlation between specific formins mRNA expression in HER2-positive cancers. To validate these findings at the protein level, immunohistochemistry was performed on HER2 subtype breast cancer tumors to establish the links between staining patterns and clinical characteristics. We then knocked down individual or combined formins in MDA-MB-453 and SK-BR-3 cells and investigated their effects on wound healing, transwell migration, and proliferation. Furthermore, we investigated the effects of erb-b2 receptor tyrosine kinase 2 (ERBB2)/HER2 small interfering RNA (siRNA)-mediated knockdown on the PI3K/Akt and MEK/ERK1 pathways as well as on selected formins. Results: Our results revealed that correlations between INF2, FHOD1, and DAAM1 mRNA expression and ERBB2 in HER2-subtype breast cancer were associated with worse outcomes. Using immunohistochemistry, we found that high FHOD1 protein expression was linked to higher histological grades and was negatively correlated with estrogen and progesterone receptor positivity. Upon formins knockdown, we observed effects on wound healing and transwell migration, with a minimal impact on proliferation, which was evident through single and combined knockdowns in both cell lines. Notably, siRNA-mediated knockdown of HER2 affected FHOD1 and INF2 expression, along with the phosphorylated Akt/MAPK states. Conclusion: Our study highlights the roles of FHOD1 and INF2 as downstream effectors of the HER2/Akt and HER2/MAPK pathways, suggesting that they are potential therapeutic targets in HER2-positive breast cancer.

      • KCI등재

        CAR links hypoxia signaling to improved survival after myocardial infarction

        Freiberg Fabian,Thakkar Meghna,Hamann Wiebke,Jacobo Lopez Carballo,Jüttner Rene,Voss Felizia K.,Becher Peter M.,Westermann Dirk,Tschöpe Carsten,Heuser Arnd,Rocks Oliver,Robert Fischer,Gotthardt Michae 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

        The coxsackievirus and adenovirus receptor (CAR) mediates homo- and heterotopic interactions between neighboring cardiomyocytes at the intercalated disc. CAR is upregulated in the hypoxic areas surrounding myocardial infarction (MI). To elucidate whether CAR contributes to hypoxia signaling and MI pathology, we used a gain- and loss-of-function approach in transfected HEK293 cells, H9c2 cardiomyocytes and CAR knockout mice. CAR overexpression increased RhoA activity, HIF-1α expression and cell death in response to chemical and physical hypoxia. In vivo, we subjected cardiomyocyte-specific CAR knockout (KO) and wild-type mice (WT) to coronary artery ligation. Survival was drastically improved in KO mice with largely preserved cardiac function as determined by echocardiography. Histological analysis revealed a less fibrotic, more compact lesion. Thirty days after MI, there was no compensatory hypertrophy or reduced cardiac output in hearts from CAR KO mice, in contrast to control mice with increased heart weight and reduced ejection fraction as signs of the underlying pathology. Based on these findings, we suggest CAR as a therapeutic target for the improved future treatment or prevention of myocardial infarction.

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