TY  - JOUR
AB  - Alzheimer's disease (AD) is defined by β-amyloid plaques and tau-containing neurofibrillary tangles, but the ensuing cellular derangements that culminate in neurodegeneration remain elusive. Here, a mechanistic link between two AD pathophysiological hallmarks: energy insufficiency and oxidative stress is revealed. It is demonstrated that mitochondrial function and glutathione (GSH) flux are coupled, impacting neuronal ferroptosis susceptibility. Analysis of proteomic data from the inferior temporal cortex of 625 subjects along a continuum of clinical and pathological changes in AD, reveals a prominent depletion of mitochondrial proteins. Biogenetic insufficiency in AD is reflected by a concurrent loss of GSH, which requires 2 ATP for its synthesis, and genetic and pharmacologic ATP depletion models confirm that ATP is rate-limiting for GSH. Accordingly, an unbiased association analysis uncovers mitochondrial proteins in positive correlation with total GSH (t-GSH) in AD subjects. But mitochondria also consume GSH via the SLC25A39 transporter. It is found that mitochondrial inhibition either increases or decreases ferroptosis susceptibility in cellular models, depending on contextual factors that dictate whether mitochondria act as a net GSH producer or consumer, respectively. Mitochondria therefore control GSH flux, and loss of energy output is consequently demonstrated as a liability for ferroptosis in AD.
AU  - Alves, F.*
AU  - Lane, D.*
AU  - Wahida, A.
AU  - Jakaria, M.*
AU  - Kalinowski, P.*
AU  - Southon, A.*
AU  - Belaidi, A.A.*
AU  - Samperi-Esteve, T.*
AU  - Nguyen, T.P.M.*
AU  - Lei, P.*
AU  - Krueger, M.*
AU  - Mueller, S.*
AU  - Conrad, M.
AU  - Agarwal, P.*
AU  - Leurgans, S.E.*
AU  - Schneider, J.*
AU  - Bush, A.I.*
AU  - Ayton, S.*
C1  - 75090
C2  - 57797
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Aberrant mitochondrial metabolism in Alzheimer's disease links energy stress with ferroptosis.
JO  - Adv. Sci.
PB  - Wiley
PY  - 2025
SN  - 2198-3844
ER  - 

TY  - JOUR
AB  - Engineering functional 3D tissue constructs is essential for developing advanced organ-like systems, with applications ranging from fundamental biological research to drug testing. The generation of complex multicellular structures requires the integration of external geometric and mechanical cues with the ability to activate genetic programs that regulate and stimulate cellular self-organization. Here, it is demonstrated that gelatin methacryloyl (GelMA) hydrogels serve as effective matrices for 3D cell culture, supporting both in situ genetic manipulation and cell growth. HEK293T cells embedded in GelMA remained viable and proliferated over 16 days, forming clusters within the matrix. Efficient gene delivery is achieved in the 3D hydrogel environment using both plasmid DNA and mRNA as gene vectors. Furthermore, in situ prime editing is applied to induce permanent genetic modifications in embedded cells. To achieve spatially confined gene expression, gel-embedded channels are introduced that allowed localized stimulation via doxycycline perfusion through a Tet-On system. These findings demonstrate the feasibility of integrating gene delivery, inducible expression, and spatial control within GelMA-based hydrogels, establishing a versatile framework for engineered 3D cell systems with programmable genetic activity.
AU  - Jäkel, A.C.*
AU  - Truong, D.J.J.
AU  - Simmel, F.C.*
C1  - 75107
C2  - 57815
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Genetic manipulation of mammalian cells in microphysiological hydrogels.
JO  - Adv. Sci.
PB  - Wiley
PY  - 2025
SN  - 2198-3844
ER  - 

TY  - JOUR
AB  - Type 1 diabetes mellitus (T1DM) is characterized by absolute insulin deficiency primarily due to autoimmune destruction of pancreatic β-cells. The prevailing treatment for T1DM involves daily subcutaneous insulin injections, but a substantial proportion of patients face challenges such as severe hypoglycemic episodes and poorly controlled hyperglycemia. For T1DM patients, a more effective therapeutic option involves the replacement of β-cells through allogeneic transplantation of either the entire pancreas or isolated pancreatic islets. Unfortunately, the scarcity of transplantable human organs has led to a growing list of patients waiting for an islet transplant. One potential alternative is xenotransplantation of porcine pancreatic islets. However, due to inter-species molecular incompatibilities, porcine tissues trigger a robust immune response in humans, leading to xenograft rejection. Several promising strategies aim to overcome this challenge and enhance the long-term survival and functionality of xenogeneic islet grafts. These strategies include the use of islets derived from genetically modified pigs, immunoisolation of islets by encapsulation in biocompatible materials, and the creation of an immunomodulatory microenvironment by co-transplanting islets with accessory cells or utilizing immunomodulatory biomaterials. This review concentrates on delineating the primary obstacles in islet xenotransplantation and elucidates the fundamental principles and recent breakthroughs aimed at addressing these challenges.
AU  - Grimus, S.*
AU  - Sarangova, V.*
AU  - Welzel, P.B.*
AU  - Ludwig, B.
AU  - Seissler, J.*
AU  - Kemter, E.*
AU  - Wolf, E.*
AU  - Ali, A.*
C1  - 70858
C2  - 55765
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Immunoprotection strategies in β-Cell replacement therapy: A closer look at porcine islet xenotransplantation.
JO  - Adv. Sci.
PB  - Wiley
PY  - 2024
SN  - 2198-3844
ER  - 

TY  - JOUR
AB  - Exposure to nanoparticles (NPs) is frequently associated with adverse cardiovascular effects. In contrast, NPs in nanomedicine hold great promise for precise lung-specific drug delivery, especially considering the extensive pulmonary capillary network that facilitates interactions with bloodstream-suspended particles. Therefore, exact knowledge about effects of engineered NPs within the pulmonary microcirculation are instrumental for future application of this technology in patients. To unravel the real-time dynamics of intravenously delivered NPs and their effects in the pulmonary microvasculature, we employed intravital microscopy of the mouse lung. Only PEG-amine-QDs, but not carboxyl-QDs triggered rapid neutrophil recruitment in microvessels and their subsequent recruitment to the alveolar space and was linked to cellular degranulation, TNF-α, and DAMP release into the circulation, particularly eATP. Stimulation of the ATP-gated receptor P2X7R induced expression of E-selectin on microvascular endothelium thereby mediating the neutrophilic immune response. Leukocyte integrins LFA-1 and MAC-1 facilitated adhesion and decelerated neutrophil crawling on the vascular surface. In summary, this study unravels the complex cascade of neutrophil recruitment during NP-induced sterile inflammation. Thereby we demonstrate novel adverse effects for NPs in the pulmonary microcirculation and provide critical insights for optimizing NP-based drug delivery and therapeutic intervention strategies, to ensure their efficacy and safety in clinical applications.
AU  - Li, C.
AU  - Liu, Q.
AU  - Han, L.
AU  - Zhang, H.
AU  - Immler, R.*
AU  - Rathkolb, B.
AU  - Secklehner, J.*
AU  - Hrabě de Angelis, M.
AU  - Yildirim, A.Ö.
AU  - Zeuschner, D.*
AU  - Nicke, A.*
AU  - Carlin, L.M.*
AU  - Sperandio, M.*
AU  - Stöger, T.
AU  - Rehberg, M.
C1  - 71910
C2  - 56296
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - The eATP/P2×7R axis drives quantum dot-nanoparticle induced neutrophil recruitment in the pulmonary microcirculation.
JO  - Adv. Sci.
PB  - Wiley
PY  - 2024
SN  - 2198-3844
ER  - 

TY  - JOUR
AB  - Cancer cells must develop strategies to adapt to the dynamically changing stresses caused by intrinsic or extrinsic processes, or therapeutic agents. Metabolic adaptability is crucial to mitigate such challenges. Considering metabolism as a central node of adaptability, it is focused on an energy sensor, the AMP-activated protein kinase (AMPK). In a subtype of pancreatic ductal adenocarcinoma (PDAC) elevated AMPK expression and phosphorylation is identified. Using drug repurposing that combined screening experiments and chemoproteomic affinity profiling, it is identified and characterized PF-3758309, initially developed as an inhibitor of PAK4, as an AMPK inhibitor. PF-3758309 shows activity in pre-clinical PDAC models, including primary patient-derived organoids. Genetic loss-of-function experiments showed that AMPK limits the induction of ferroptosis, and consequently, PF-3758309 treatment restores the sensitivity toward ferroptosis inducers. The work established a chemical scaffold for the development of specific AMPK-targeting compounds and deciphered the framework for the development of AMPK inhibitor-based combination therapies tailored for PDAC.
AU  - Schneider, C.*
AU  - Hilbert, J.*
AU  - Genevaux, F.*
AU  - Höfer, S.*
AU  - Kraus, L.*
AU  - Schicktanz, F.*
AU  - Contreras, C.T.*
AU  - Jansari, S.*
AU  - Papargyriou, A.
AU  - Richter, T.*
AU  - Alfayomy, A.M.*
AU  - Falcomatà, C.*
AU  - Schneeweis, C.*
AU  - Orben, F.*
AU  - Öllinger, R.*
AU  - Wegwitz, F.*
AU  - Boshnakovska, A.*
AU  - Rehling, P.*
AU  - Müller, D.*
AU  - Ströbel, P.*
AU  - Ellenrieder, V.*
AU  - Conradi, L.*
AU  - Hessmann, E.*
AU  - Ghadimi, M.*
AU  - Grade, M.*
AU  - Wirth, M.*
AU  - Steiger, K.*
AU  - Rad, R.*
AU  - Kuster, B.*
AU  - Sippl, W.*
AU  - Reichert, M.*
AU  - Saur, D.*
AU  - Schneider, G.*
C1  - 70856
C2  - 55764
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - A novel AMPK inhibitor sensitizes pancreatic cancer cells to ferroptosis induction.
JO  - Adv. Sci.
PB  - Wiley
PY  - 2024
SN  - 2198-3844
ER  - 

TY  - JOUR
AB  - Intracellular delivery of nano-drug-carriers (NDC) to specific cells, diseased regions, or solid tumors has entered the era of precision medicine that requires systematic knowledge of nano-biological interactions from multidisciplinary perspectives. To this end, this review first provides an overview of membrane-disruption methods such as electroporation, sonoporation, photoporation, microfluidic delivery, and microinjection with the merits of high-throughput and enhanced efficiency for in vitro NDC delivery. The impact of NDC characteristics including particle size, shape, charge, hydrophobicity, and elasticity on cellular uptake are elaborated and several types of NDC systems aiming for hierarchical targeting and delivery in vivo are reviewed. Emerging in vitro or ex vivo human/animal-derived pathophysiological models are further explored and highly recommended for use in NDC studies since they might mimic in vivo delivery features and fill the translational gaps from animals to humans. The exploration of modern microscopy techniques for precise nanoparticle (NP) tracking at the cellular, organ, and organismal levels informs the tailored development of NDCs for in vivo application and clinical translation. Overall, the review integrates the latest insights into smart nanosystem engineering, physiological models, imaging-based validation tools, all directed towards enhancing the precise and efficient intracellular delivery of NDCs.
AU  - Zhou, Q.
AU  - Liu, Q.
AU  - Wang, Y.*
AU  - Chen, J.*
AU  - Schmid, O.
AU  - Rehberg, M.
AU  - Yang, L.
C1  - 69848
C2  - 55280
TI  - Bridging smart nanosystems with clinically relevant models and advanced imaging for precision drug delivery.
JO  - Adv. Sci.
VL  - 11
IS  - 14
PY  - 2024
SN  - 2198-3844
ER  - 

TY  - JOUR
AB  - Sex disparities in serum bile acid (BA) levels and Alzheimer's disease (AD) prevalence have been established. However, the precise link between changes in serum BAs and AD development remains elusive. Here, authors quantitatively determined 33 serum BAs and 58 BA features in 4 219 samples collected from 1 180 participants from the Alzheimer's Disease Neuroimaging Initiative. The findings revealed that these BA features exhibited significant correlations with clinical stages, encompassing cognitively normal (CN), early and late mild cognitive impairment, and AD, as well as cognitive performance. Importantly, these associations are more pronounced in men than women. Among participants with progressive disease stages (n = 660), BAs underwent early changes in men, occurring before AD. By incorporating BA features into diagnostic and predictive models, positive enhancements are achieved for all models. The area under the receiver operating characteristic curve improved from 0.78 to 0.91 for men and from 0.76 to 0.83 for women for the differentiation of CN and AD. Additionally, the key findings are validated in a subset of participants (n = 578) with cerebrospinal fluid amyloid-beta and tau levels. These findings underscore the role of BAs in AD progression, offering potential improvements in the accuracy of AD prediction.
AU  - Chen, T.*
AU  - Wang, L.*
AU  - Xie, G.*
AU  - Kristal, B.S.*
AU  - Zheng, X.*
AU  - Sun, T.*
AU  - Arnold, M.
AU  - Louie, G.*
AU  - Li, M.*
AU  - Wu, L.*
AU  - MahmoudianDehkordi, S.*
AU  - Sniatynski, M.J.*
AU  - Borkowski, K.*
AU  - Guo, Q.*
AU  - Kuang, J.*
AU  - Wang, J.*
AU  - Nho, K.*
AU  - Ren, Z.*
AU  - Kueider-Paisley, A.*
AU  - Blach, C.*
AU  - Kaddurah-Daouk, R.*
AU  - Jia, W.*
C1  - 68974
C2  - 53792
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Serum bile acids improve prediction of Alzheimer's progression in a sex-dependent manner.
JO  - Adv. Sci.
PB  - Wiley
PY  - 2023
SN  - 2198-3844
ER  - 

TY  - JOUR
AB  - Various morphological and functional parameters of peripheral nerves and their vascular supply are indicative of pathological changes due to injury or disease. Based on recent improvements in optoacoustic image quality, the ability of multispectral optoacoustic tomography, to investigate the vascular environment and morphology of peripheral nerves is explored in vivo in a pilot study on healthy volunteers in tandem with ultrasound imaging (OPUS). The unique ability of optoacoustic imaging to visualize the vasa nervorum by observing intraneural vessels in healthy nerves is showcased in vivo for the first time. In addition, it is demonstrated that the label-free spectral optoacoustic contrast of the perfused connective tissue of peripheral nerves can be linked to the endogenous contrast of hemoglobin and collagen. Metrics are introduced to analyze the composition of tissue based on its optoacoustic contrast and show that the high-resolution spectral contrast reveals specific differences between nervous tissue and reference tissue in the nerve's surrounding. How this showcased extraction of peripheral nerve characteristics using multispectral optoacoustic and ultrasound imaging could offer new insights into the pathophysiology of nerve damage and neuropathies, for example, in the context of diabetes is discussed.
AU  - Jüstel, D.
AU  - Irl, H.*
AU  - Hinterwimmer, F.*
AU  - Dehner, C.
AU  - Simson, W.*
AU  - Navab, N.*
AU  - Schneider, G.*
AU  - Ntziachristos, V.
C1  - 67671
C2  - 53978
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Spotlight on nerves: Portable multispectral optoacoustic imaging of peripheral nerve vascularization and morphology.
JO  - Adv. Sci.
VL  - 10
IS  - 19
PB  - Wiley
PY  - 2023
SN  - 2198-3844
ER  - 

TY  - JOUR
AB  - Astrocytes have crucial functions in the central nervous system (CNS) and are major players in many CNS diseases. Research on astrocyte-centered diseases requires efficient and well-characterized gene transfer vectors. Vectors derived from the Adeno-associated virus serotype 9 (AAV9) target astrocytes in the brains of rodents and nonhuman primates. A recombinant (r) synthetic peptide-displaying AAV9 variant, rAAV9P1, that efficiently and selectively transduces cultured human astrocytes, has been described previously. Here, it is shown that rAAV9P1 retains astrocyte-targeting properties upon intravenous injection in mice. Detailed analysis of putative receptors on human astrocytes shows that rAAV9P1 utilizes integrin subunits αv, β8, and either β3 or β5 as well as the AAV receptor AAVR. This receptor pattern is distinct from that of vectors derived from wildtype AAV2 or AAV9. Furthermore, a CRISPR/Cas9 genome-wide knockout screening revealed the involvement of several astrocyte-associated intracellular signaling pathways in the transduction of human astrocytes by rAAV9P1. This study delineates the unique receptor and intracellular pathway signatures utilized by rAAV9P1 for targeting human astrocytes. These results enhance the understanding of the transduction biology of synthetic rAAV vectors for astrocytes and can promote the development of advanced astrocyte-selective gene delivery vehicles for research and clinical applications.
AU  - Bauer, A.
AU  - Puglisi, M.
AU  - Nagl, D.*
AU  - Schick, J.
AU  - Werner, T.*
AU  - Klingl, A.*
AU  - El Andari, J.*
AU  - Hornung, V.*
AU  - Kessler, H.*
AU  - Götz, M.
AU  - Grimm, D.*
AU  - Brack-Werner, R.
C1  - 64752
C2  - 51929
TI  - Molecular signature of astrocytes for gene delivery by the synthetic adeno-associated viral vector rAAV9P1.
JO  - Adv. Sci.
PY  - 2022
SN  - 2198-3844
ER  - 

TY  - JOUR
AB  - Aberrant energy metabolism and cell cycle regulation both critically contribute to malignant cell growth and both processes represent targets for anticancer therapy. It is shown here that depletion of the AAA+-ATPase thyroid hormone receptor interacting protein 13 (Trip13) results in mitotic cell death through a combined mechanism linking lipid metabolism to aberrant mitosis. Diminished Trip13 levels in hepatocellular carcinoma cells result in insulin-receptor-/Akt-pathway-dependent accumulation of lipid droplets, which act as functional acentriolar microtubule organizing centers disturbing mitotic spindle polarity. Specifically, the lipid-droplet-coating protein perilipin 2 (Plin2) is required for multipolar spindle formation, induction of DNA damage, and mitotic cell death. Plin2 expression in different tumor cells confers susceptibility to cell death induced by Trip13 depletion as well as treatment with paclitaxel, a spindle-interfering drug commonly used against different cancers. Thus, assessment of Plin2 levels enables the stratification of tumor responsiveness to mitosis-targeting drugs, including clinically approved paclitaxel and Trip13 inhibitors currently under development.
AU  - Rios Garcia, M.
AU  - Meissburger, B.*
AU  - Chan, J.
AU  - de Guia, R.M.*
AU  - Mattijssen, F.
AU  - Roessler, S.*
AU  - Birkenfeld, A.L.
AU  - Raschzok, N.*
AU  - Riols, F.
AU  - Tokarz, J.
AU  - Giroud, M.
AU  - Gil Lozano, M.
AU  - Hartleben, G.
AU  - Nawroth, P.P.
AU  - Haid, M.
AU  - López, M.*
AU  - Herzig, S.
AU  - Berriel Diaz, M.
C1  - 65964
C2  - 52818
TI  - Trip13 depletion in liver cancer induces a lipogenic response contributing to plin2-dependent mitotic cell death.
JO  - Adv. Sci.
VL  - 9
IS  - 29
PY  - 2022
SN  - 2198-3844
ER  - 

TY  - JOUR
AB  - Somatic cell reprogramming and tissue repair share relevant factors and molecular programs. Here, Dickkopf-3 (DKK3) is identified as novel factor for organ regeneration using combined transcription-factor-induced reprogramming and RNA-interference techniques. Loss of Dkk3 enhances the generation of induced pluripotent stem cells but does not affect de novo derivation of embryonic stem cells, three-germ-layer differentiation or colony formation capacity of liver and pancreatic organoids. However, DKK3 expression levels in wildtype animals and serum levels in human patients are elevated upon injury. Accordingly, Dkk3-null mice display less liver damage upon acute and chronic failure mediated by increased proliferation in hepatocytes and LGR5  liver progenitor cell population, respectively. Similarly, recovery from experimental pancreatitis is accelerated. Regeneration onset occurs in the acinar compartment accompanied by virtually abolished canonical-Wnt-signaling in Dkk3-null animals. This results in reduced expression of the Hedgehog repressor Gli3 and increased Hedgehog-signaling activity upon Dkk3 loss. Collectively, these data reveal Dkk3 as a key regulator of organ regeneration via a direct, previously unacknowledged link between DKK3, canonical-Wnt-, and Hedgehog-signaling. +
AU  - Arnold, F.*
AU  - Mahaddalkar, P.U.
AU  - Kraus, J.M.*
AU  - Zhong, X.*
AU  - Bergmann, W.*
AU  - Srinivasan, D.*
AU  - Gout, J.*
AU  - Roger, E.*
AU  - Beutel, A.K.*
AU  - Zizer, E.*
AU  - Tharehalli, U.*
AU  - Daiss, N.*
AU  - Russell, R.*
AU  - Perkhofer, L.*
AU  - Oellinger, R.*
AU  - Lin, Q.S.*
AU  - Azoitei, N.*
AU  - Weiss, F.U.*
AU  - Lerch, M.M.*
AU  - Liebau, S.*
AU  - Katz, S.F.*
AU  - Lechel, A.*
AU  - Rad, R.*
AU  - Seufferlein, T.*
AU  - Kestler, H.A.*
AU  - Ott, M.*
AU  - Sharma, A.D.*
AU  - Hermann, P.C.*
AU  - Kleger, A.*
C1  - 62053
C2  - 50618
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Functional genomic screening during somatic cell reprogramming identifies DKK3 as a roadblock of organ regeneration.
JO  - Adv. Sci.
VL  - 8
IS  - 14
PB  - Wiley
PY  - 2021
SN  - 2198-3844
ER  - 

TY  - JOUR
AB  - Type 2 diabetes is a metabolic, chronic disorder characterized by insulin resistance and elevated blood glucose levels. Although a large drug portfolio exists to keep the blood glucose levels under control, these medications are not without side effects. More importantly, once diagnosed diabetes is rarely reversible. Dysfunctions in the kidney, retina, cardiovascular system, neurons, and liver represent the common complications of diabetes, which again lack effective therapies that can reverse organ injury. Overall, the molecular mechanisms of how type 2 diabetes develops and leads to irreparable organ damage remain elusive. This review particularly focuses on novel targets that may play role in pathogenesis of type 2 diabetes. Further research on these targets may eventually pave the way to novel therapies for the treatment—or even the prevention—of type 2 diabetes along with its complications.
AU  - Demir, S.
AU  - Nawroth, P.P.
AU  - Herzig, S.
AU  - Ekim Üstünel, B.
C1  - 62711
C2  - 50982
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
SP  - e2100275
TI  - Emerging targets in type 2 diabetes and diabetic complications.
JO  - Adv. Sci.
PB  - Wiley
PY  - 2021
SN  - 2198-3844
ER  - 

TY  - JOUR
AB  - Increased acrolein (ACR), a toxic metabolite derived from energy consumption, is associated with diabetes and its complications. However, the molecular mechanisms are mostly unknown, and a suitable animal model with internal increased ACR does not exist for in vivo studying so far. Several enzyme systems are responsible for acrolein detoxification, such as Aldehyde Dehydrogenase (ALDH), Aldo-Keto Reductase (AKR), and Glutathione S-Transferase (GST). To evaluate the function of ACR in glucose homeostasis and diabetes, akr1a1a-/- zebrafish mutants are generated using CRISPR/Cas9 technology. Accumulated endogenous acrolein is confirmed in akr1a1a-/- larvae and livers of adults. Moreover, a series of experiments are performed regarding organic alterations, the glucose homeostasis, transcriptome, and metabolomics in Tg(fli1:EGFP) zebrafish. Akr1a1a-/- larvae display impaired glucose homeostasis and angiogenic retina hyaloid vasculature, which are caused by reduced acrolein detoxification ability and increased internal ACR concentration. The effects of acrolein on hyaloid vasculature can be reversed by acrolein-scavenger l-carnosine treatment. In adult akr1a1a-/- mutants, impaired glucose tolerance accompanied by angiogenic retina vessels and glomerular basement membrane thickening, consistent with an early pathological appearance in diabetic retinopathy and nephropathy, are observed. Thus, the data strongly suggest impaired ACR detoxification and elevated ACR concentration as biomarkers and inducers for diabetes and diabetic complications.
AU  - Qi, H.*
AU  - Schmöhl, F.*
AU  - Li, X.*
AU  - Qian, X.*
AU  - Tabler, C.T.*
AU  - Bennewitz, K.*
AU  - Sticht, C.*
AU  - Morgenstern, J.*
AU  - Fleming, T.*
AU  - Volk, N.*
AU  - Hausser, I.*
AU  - Heidenreich, E.*
AU  - Hell, R.*
AU  - Nawroth, P.P.
AU  - Kroll, J.*
C1  - 62557
C2  - 50818
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Reduced acrolein detoxification in akr1a1a zebrafish mutants causes impaired insulin receptor signaling and microvascular alterations.
JO  - Adv. Sci.
VL  - 8
IS  - 18
PB  - Wiley
PY  - 2021
SN  - 2198-3844
ER  - 

TY  - JOUR
AB  - Human adenoviruses (HAdV) are associated with clinical symptoms such as gastroenteritis, keratoconjunctivitis, pneumonia, hepatitis, and encephalitis. In the absence of protective immunity, as in allogeneic bone marrow transplant patients, HAdV infections can become lethal. Alarmingly, various outbreaks of highly pathogenic, pneumotropic HAdV types have been recently reported, causing severe and lethal respiratory diseases. Effective drugs for treatment of HAdV infections are still lacking. The repurposing of drugs approved for other indications is a valuable alternative for the development of new antiviral therapies and is less risky and costly than de novo development. Arsenic trioxide (ATO) is approved for treatment of acute promyelocytic leukemia. Here, it is shown that ATO is a potent inhibitor of HAdV. ATO treatment blocks virus expression and replication by reducing the number and integrity of promyelocytic leukemia (PML) nuclear bodies, important subnuclear structures for HAdV replication. Modification of HAdV proteins with small ubiquitin-like modifiers (SUMO) is also key to HAdV replication. ATO reduces levels of viral SUMO-E2A protein, while increasing SUMO-PML, suggesting that ATO interferes with SUMOylation of proteins crucial for HAdV replication. It is concluded that ATO targets cellular processes key to HAdV replication and is relevant for the development of antiviral intervention strategies.
AU  - Hofmann, S.*
AU  - Mai, J.*
AU  - Masser, S.*
AU  - Groitl, P.*
AU  - Herrmann, A.
AU  - Sternsdorf, T.*
AU  - Brack-Werner, R.
AU  - Schreiner, S.
C1  - 58528
C2  - 48239
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - ATO (Arsenic Trioxide) effects on promyelocytic leukemia nuclear bodies reveals antiviral intervention capacity.
JO  - Adv. Sci.
VL  - 7
IS  - 8
PB  - Wiley
PY  - 2020
SN  - 2198-3844
ER  - 

TY  - JOUR
AB  - Red blood cells are "shaken" with a holographic optical tweezer array. The flow generated around cells due to the periodic optical forcing is measured with an optically trapped "detector" particle located in the cell vicinity. A signal-processing model that describes the cell's physical properties as an analog filter illustrates how cells can be distinguished from each other.
AU  - Zensen, C.*
AU  - Fernandez, I.E.
AU  - Eickelberg, O.
AU  - Feldmann, J.*
AU  - Lohmüller, T.*
C1  - 50626
C2  - 42654
CY  - Hoboken
TI  - Detecting swelling states of red blood cells by "Cell-fluid coupling spectroscopy".
JO  - Adv. Sci.
VL  - 4
IS  - 2
PB  - Wiley
PY  - 2017
SN  - 2198-3844
ER  -