TY - JOUR A1 - Kotnik, Katarina A1 - Popova, Elena A1 - Todiras, Mihail A1 - Mori, Marcelo A. A1 - Alenina, Natalia A1 - Seibler, Jost A1 - Bader, Michael T1 - Inducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown JF - Plos One Y1 - 2009 U6 - http://dx.doi.org/10.1371/journal.pone.0005124 VL - 4 IS - 4 SP - e5124 PB - Plos CY - San Francisco, California, US ER - TY - JOUR A1 - Stiemer, Luc Nicolas A1 - Thoma, Andreas A1 - Braun, Carsten T1 - MBT3D: Deep learning based multi-object tracker for bumblebee 3D flight path estimation JF - PLoS ONE N2 - This work presents the Multi-Bees-Tracker (MBT3D) algorithm, a Python framework implementing a deep association tracker for Tracking-By-Detection, to address the challenging task of tracking flight paths of bumblebees in a social group. While tracking algorithms for bumblebees exist, they often come with intensive restrictions, such as the need for sufficient lighting, high contrast between the animal and background, absence of occlusion, significant user input, etc. Tracking flight paths of bumblebees in a social group is challenging. They suddenly adjust movements and change their appearance during different wing beat states while exhibiting significant similarities in their individual appearance. The MBT3D tracker, developed in this research, is an adaptation of an existing ant tracking algorithm for bumblebee tracking. It incorporates an offline trained appearance descriptor along with a Kalman Filter for appearance and motion matching. Different detector architectures for upstream detections (You Only Look Once (YOLOv5), Faster Region Proposal Convolutional Neural Network (Faster R-CNN), and RetinaNet) are investigated in a comparative study to optimize performance. The detection models were trained on a dataset containing 11359 labeled bumblebee images. YOLOv5 reaches an Average Precision of AP = 53, 8%, Faster R-CNN achieves AP = 45, 3% and RetinaNet AP = 38, 4% on the bumblebee validation dataset, which consists of 1323 labeled bumblebee images. The tracker’s appearance model is trained on 144 samples. The tracker (with Faster R-CNN detections) reaches a Multiple Object Tracking Accuracy MOTA = 93, 5% and a Multiple Object Tracking Precision MOTP = 75, 6% on a validation dataset containing 2000 images, competing with state-of-the-art computer vision methods. The framework allows reliable tracking of different bumblebees in the same video stream with rarely occurring identity switches (IDS). MBT3D has much lower IDS than other commonly used algorithms, with one of the lowest false positive rates, competing with state-of-the-art animal tracking algorithms. The developed framework reconstructs the 3-dimensional (3D) flight paths of the bumblebees by triangulation. It also handles and compares two alternative stereo camera pairs if desired. Y1 - 2023 U6 - http://dx.doi.org/10.1371/journal.pone.0291415 SN - 1932-6203 N1 - Corresponding author: Luc Nicolas Stiemer VL - 18 IS - 9 PB - PLOS CY - San Fancisco ER - TY - JOUR A1 - Prochnow, Nora A1 - Gebing, Tina A1 - Ladage, Kerstin A1 - Krause-Finkeldey, Dorothee A1 - Ourdi, Abessamad El A1 - Bitz, Andreas A1 - Streckert, Joachim A1 - Hansen, Volkert A1 - Dermietzel, Rolf T1 - Electromagnetic field effect or simply stress? Effects of UMTS exposure on hippocampal longterm plasticity in the context of procedure related hormone release JF - PLoS one N2 - Harmful effects of electromagnetic fields (EMF) on cognitive and behavioural features of humans and rodents have been controversially discussed and raised persistent concern about adverse effects of EMF on general brain functions. In the present study we applied radio-frequency (RF) signals of the Universal Mobile Telecommunications System (UMTS) to full brain exposed male Wistar rats in order to elaborate putative influences on stress hormone release (corticosteron; CORT and adrenocorticotropic hormone; ACTH) and on hippocampal derived synaptic long-term plasticity (LTP) and depression (LTD) as electrophysiological hallmarks for memory storage and memory consolidation. Exposure was computer controlled providing blind conditions. Nominal brain-averaged specific absorption rates (SAR) as a measure of applied mass-related dissipated RF power were 0, 2, and 10 W/kg over a period of 120 min. Comparison of cage exposed animals revealed, regardless of EMF exposure, significantly increased CORT and ACTH levels which corresponded with generally decreased field potential slopes and amplitudes in hippocampal LTP and LTD. Animals following SAR exposure of 2 W/kg (averaged over the whole brain of 2.3 g tissue mass) did not differ from the sham-exposed group in LTP and LTD experiments. In contrast, a significant reduction in LTP and LTD was observed at the high power rate of SAR (10 W/kg). The results demonstrate that a rate of 2 W/kg displays no adverse impact on LTP and LTD, while 10 W/kg leads to significant effects on the electrophysiological parameters, which can be clearly distinguished from the stress derived background. Our findings suggest that UMTS exposure with SAR in the range of 2 W/kg is not harmful to critical markers for memory storage and memory consolidation, however, an influence of UMTS at high energy absorption rates (10 W/kg) cannot be excluded. Y1 - 2011 U6 - http://dx.doi.org/10.1371/journal.pone.0019437 VL - 6 IS - 5 PB - PLOS CY - San Francisco ER - TY - JOUR A1 - Albanna, Walid A1 - Kotliar, Konstantin A1 - Lüke, Jan Niklas A1 - Alpdogan, Serdar A1 - Conzen, Catharina A1 - Lindauer, Ute A1 - Clusmann, Hans A1 - Hescheler, Jürgen A1 - Vilser, Walthard A1 - Schneider, Toni A1 - Schubert, Gerrit Alexander T1 - Non-invasive evaluation of neurovascular coupling in the murine retina by dynamic retinal vessel analysis JF - Plos one N2 - Background Impairment of neurovascular coupling (NVC) was recently reported in the context of subarachnoid hemorrhage and may correlate with disease severity and outcome. However, previous techniques to evaluate NVC required invasive procedures. Retinal vessels may represent an alternative option for non-invasive assessment of NVC. Methods A prototype of an adapted retinal vessel analyzer was used to assess retinal vessel diameter in mice. Dynamic vessel analysis (DVA) included an application of monochromatic flicker light impulses in predefined frequencies for evaluating NVC. All retinae were harvested after DVA and electroretinograms were performed. Results A total of 104 retinal scans were conducted in 21 male mice (90 scans). Quantitative arterial recordings were feasible only in a minority of animals, showing an emphasized reaction to flicker light impulses (8 mice; 14 scans). A characteristic venous response to flicker light, however, could observed in the majority of animals. Repeated measurements resulted in a significant decrease of baseline venous diameter (7 mice; 7 scans, p < 0.05). Ex-vivo electroretinograms, performed after in-vivo DVA, demonstrated a significant reduction of transretinal signaling in animals with repeated DVA (n = 6, p < 0.001). Conclusions To the best of our knowledge, this is the first non-invasive study assessing murine retinal vessel response to flicker light with characteristic changes in NVC. The imaging system can be used for basic research and enables the investigation of retinal vessel dimension and function in control mice and genetically modified animals. Y1 - 2018 U6 - http://dx.doi.org/10.1371/journal.pone.0204689 VL - 13 IS - 10 PB - PLOS CY - San Francisco ER - TY - JOUR A1 - Theysohn, Jens M. A1 - Kraff, Oliver A1 - Eilers, Kristina A1 - Andrade, Dorian A1 - Gerwig, Marcus A1 - Timmann, Dagmar A1 - Schmitt, Franz A1 - Ladd, Mark E. A1 - Ladd, Susanne C. A1 - Bitz, Andreas T1 - Vestibular effects of a 7 Tesla MRI examination compared to 1.5 T and 0 T in healthy volunteers JF - PLoS one N2 - Ultra-high-field MRI (7 Tesla (T) and above) elicits more temporary side-effects compared to 1.5 T and 3 T, e.g. dizziness or “postural instability” even after exiting the scanner. The current study aims to assess quantitatively vestibular performance before and after exposure to different MRI scenarios at 7 T, 1.5 T and 0 T. Sway path and body axis rotation (Unterberger's stepping test) were quantitatively recorded in a total of 46 volunteers before, 2 minutes after, and 15 minutes after different exposure scenarios: 7 T head MRI (n = 27), 7 T no RF (n = 22), 7 T only B₀ (n = 20), 7 T in & out B₀ (n = 20), 1.5 T no RF (n = 20), 0 T (n = 15). All exposure scenarios lasted 30 minutes except for brief one minute exposure in 7 T in & out B₀. Both measures were documented utilizing a 3D ultrasound system. During sway path evaluation, the experiment was repeated with eyes both open and closed. Sway paths for all long-lasting 7 T scenarios (normal, no RF, only B₀) with eyes closed were significantly prolonged 2 minutes after exiting the scanner, normalizing after 15 minutes. Brief exposure to 7 T B₀ or 30 minutes exposure to 1.5 T or 0 T did not show significant changes. End positions after Unterberger's stepping test were significantly changed counter-clockwise after all 7 T scenarios, including the brief in & out B₀ exposure. Shorter exposure resulted in a smaller alteration angle. In contrast to sway path, reversal of changes in body axis rotation was incomplete after 15 minutes. 1.5 T caused no rotational changes. The results show that exposure to the 7 Tesla static magnetic field causes only a temporary dysfunction or “over-compensation” of the vestibular system not measurable at 1.5 or 0 Tesla. Radiofrequency fields, gradient switching, and orthostatic dysregulation do not seem to play a role. Y1 - 2014 U6 - http://dx.doi.org/10.1371/journal.pone.0092104 SN - 1932-6203 VL - 9 IS - 3 PB - PLOS CY - San Francisco ER - TY - JOUR A1 - Bialonski, Stephan A1 - Wendler, Martin A1 - Lehnertz, Klaus T1 - Unraveling spurious properties of interaction networks with tailored random networks JF - Plos one N2 - We investigate interaction networks that we derive from multivariate time series with methods frequently employed in diverse scientific fields such as biology, quantitative finance, physics, earth and climate sciences, and the neurosciences. Mimicking experimental situations, we generate time series with finite length and varying frequency content but from independent stochastic processes. Using the correlation coefficient and the maximum cross-correlation, we estimate interdependencies between these time series. With clustering coefficient and average shortest path length, we observe unweighted interaction networks, derived via thresholding the values of interdependence, to possess non-trivial topologies as compared to Erdös-Rényi networks, which would indicate small-world characteristics. These topologies reflect the mostly unavoidable finiteness of the data, which limits the reliability of typically used estimators of signal interdependence. We propose random networks that are tailored to the way interaction networks are derived from empirical data. Through an exemplary investigation of multichannel electroencephalographic recordings of epileptic seizures – known for their complex spatial and temporal dynamics – we show that such random networks help to distinguish network properties of interdependence structures related to seizure dynamics from those spuriously induced by the applied methods of analysis. Y1 - 2011 U6 - http://dx.doi.org/10.1371/journal.pone.0022826 VL - 6 IS - 8 PB - Plos CY - San Francisco ER - TY - JOUR A1 - Baumgartner, Werner A1 - Fidler, Florian A1 - Weth, Agnes A1 - Habbecke, Martin A1 - Jakob, Peter A1 - Butenweg, Christoph A1 - Böhme, Wolfgang T1 - Investigating the locomotion of the sandfish in desert sand using NMR-Imaging JF - PLOS ONE N2 - The sandfish (Scincus scincus) is a lizard having the remarkable ability to move through desert sand for significant distances. It is well adapted to living in loose sand by virtue of a combination of morphological and behavioural specializations. We investigated the bodyform of the sandfish using 3D-laserscanning and explored its locomotion in loose desert sand using fast nuclear magnetic resonance (NMR) imaging. The sandfish exhibits an in-plane meandering motion with a frequency of about 3 Hz and an amplitude of about half its body length accompanied by swimming-like (or trotting) movements of its limbs. No torsion of the body was observed, a movement required for a digging-behaviour. Simple calculations based on the Janssen model for granular material related to our findings on bodyform and locomotor behaviour render a local decompaction of the sand surrounding the moving sandfish very likely. Thus the sand locally behaves as a viscous fluid and not as a solid material. In this fluidised sand the sandfish is able to “swim” using its limbs. KW - magnetic resonance imaging KW - body limbs KW - swimming KW - lizards KW - deserts Y1 - 2008 U6 - http://dx.doi.org/10.1371/journal.pone.0003309 SN - 1932-6203 VL - 3 IS - 10 PB - Plos CY - San Francisco, California, US ER - TY - JOUR A1 - Achtsnicht, Stefan A1 - Neuendorf, Christian A1 - Faßbender, Tobias A1 - Nölke, Greta A1 - Offenhäusser, Andreas A1 - Krause, Hans-Joachim A1 - Schröper, Florian T1 - Sensitive and rapid detection of cholera toxin subunit B using magnetic frequency mixing detection JF - Plos One N2 - Cholera is a life-threatening disease caused by the cholera toxin (CT) as produced by some Vibrio cholerae serogroups. In this research we present a method which directly detects the toxin’s B subunit (CTB) in drinking water. For this purpose we performed a magnetic sandwich immunoassay inside a 3D immunofiltration column. We used two different commercially available antibodies to capture CTB and for binding to superparamagnetic beads. ELISA experiments were performed to select the antibody combination. The beads act as labels for the magnetic frequency mixing detection technique. We show that the limit of detection depends on the type of magnetic beads. A nonlinear Hill curve was fitted to the calibration measurements by means of a custom-written python software. We achieved a sensitive and rapid detection of CTB within a broad concentration range from 0.2 ng/ml to more than 700 ng/ml. Y1 - 2019 U6 - http://dx.doi.org/10.1371/journal.pone.0219356 SN - 1932-6203 VL - 14 IS - 7 PB - Plos CY - San Francisco ER - TY - JOUR A1 - Kuhnert, Marie-Therese A1 - Bialonski, Stephan A1 - Noenning, Nina A1 - Mai, Heinke A1 - Hinrichs, Hermann A1 - Helmstaedter, Christoph A1 - Lehnertz, Klaus T1 - Incidental and intentional learning of verbal episodic material differentially modifies functional brain networks JF - Plos one N2 - Learning- and memory-related processes are thought to result from dynamic interactions in large-scale brain networks that include lateral and mesial structures of the temporal lobes. We investigate the impact of incidental and intentional learning of verbal episodic material on functional brain networks that we derive from scalp-EEG recorded continuously from 33 subjects during a neuropsychological test schedule. Analyzing the networks' global statistical properties we observe that intentional but not incidental learning leads to a significantly increased clustering coefficient, and the average shortest path length remains unaffected. Moreover, network modifications correlate with subsequent recall performance: the more pronounced the modifications of the clustering coefficient, the higher the recall performance. Our findings provide novel insights into the relationship between topological aspects of functional brain networks and higher cognitive functions. Y1 - 2013 U6 - http://dx.doi.org/10.1371/journal.pone.0080273 VL - 8 IS - 11 PB - PLOS CY - San Francisco ER - TY - JOUR A1 - Herssens, Nolan A1 - Cowburn, James A1 - Albracht, Kirsten A1 - Braunstein, Bjoern A1 - Cazzola, Dario A1 - Colyer, Steffi A1 - Minetti, Alberto E. A1 - Pavei, Gaspare A1 - Rittweger, Jörn A1 - Weber, Tobias A1 - Green, David A. ED - Cattaneo, Luigi T1 - Movement in low gravity environments (MoLo) programme – the MoLo-L.O.O.P. study protocol JF - PLOS ONE / Public Library of Science N2 - Exposure to prolonged periods in microgravity is associated with deconditioning of the musculoskeletal system due to chronic changes in mechanical stimulation. Given astronauts will operate on the Lunar surface for extended periods of time, it is critical to quantify both external (e.g., ground reaction forces) and internal (e.g., joint reaction forces) loads of relevant movements performed during Lunar missions. Such knowledge is key to predict musculoskeletal deconditioning and determine appropriate exercise countermeasures associated with extended exposure to hypogravity. Y1 - 2022 U6 - http://dx.doi.org/10.1371/journal.pone.0278051 SN - 1932-6203 VL - 17 IS - 11 PB - Plos CY - San Francisco ER - TY - JOUR A1 - Schroeter, Rebecca A1 - Hoffmann, Tamara A1 - Voigt, Birgit A1 - Meyer, Hanna A1 - Bleisteiner, Monika A1 - Muntel, Jan A1 - Jürgen, Britta A1 - Albrecht, Dirk A1 - Becher, Dörte A1 - Lalk, Michael A1 - Evers, Stefan A1 - Bongaerts, Johannes A1 - Maurer, Karl-Heinz A1 - Putzer, Harald A1 - Hecker, Michael A1 - Schweder, Thomas A1 - Bremer, Erhard T1 - Stress responses of the industrial workhorse Bacillus licheniformis to osmotic challenges JF - PLoS ONE N2 - The Gram-positive endospore-forming bacterium Bacillus licheniformis can be found widely in nature and it is exploited in industrial processes for the manufacturing of antibiotics, specialty chemicals, and enzymes. Both in its varied natural habitats and in industrial settings, B. licheniformis cells will be exposed to increases in the external osmolarity, conditions that trigger water efflux, impair turgor, cause the cessation of growth, and negatively affect the productivity of cell factories in biotechnological processes. We have taken here both systems-wide and targeted physiological approaches to unravel the core of the osmostress responses of B. licheniformis. Cells were suddenly subjected to an osmotic upshift of considerable magnitude (with 1 M NaCl), and their transcriptional profile was then recorded in a time-resolved fashion on a genome-wide scale. A bioinformatics cluster analysis was used to group the osmotically up-regulated genes into categories that are functionally associated with the synthesis and import of osmostress-relieving compounds (compatible solutes), the SigB-controlled general stress response, and genes whose functional annotation suggests that salt stress triggers secondary oxidative stress responses in B. licheniformis. The data set focusing on the transcriptional profile of B. licheniformis was enriched by proteomics aimed at identifying those proteins that were accumulated by the cells through increased biosynthesis in response to osmotic stress. Furthermore, these global approaches were augmented by a set of experiments that addressed the synthesis of the compatible solutes proline and glycine betaine and assessed the growth-enhancing effects of various osmoprotectants. Combined, our data provide a blueprint of the cellular adjustment processes of B. licheniformis to both sudden and sustained osmotic stress. Y1 - 2014 U6 - http://dx.doi.org/10.1371/journal.pone.0080956 SN - 1932-6203 VL - 8 IS - 11 PB - PLOS CY - San Francisco ER - TY - JOUR A1 - Albanna, W. A1 - Conzen, C. A1 - Weiss, M. A1 - Clusmann, H. A1 - Fuest, M. A1 - Mueller, M. A1 - Brockmann, M.A. A1 - Vilser, W. A1 - Schmidt-Trucksäss, A. A1 - Hoellig, A. A1 - Seiz, M. A1 - Thomé, C. A1 - Kotliar, Konstantin A1 - Schubert, G.A. T1 - Retinal Vessel Analysis (RVA) in the context of subarachnoid hemorrhage: A proof of concept study JF - PLoS ONE N2 - Background Timely detection of impending delayed cerebral ischemia after subarachnoid hemorrhage (SAH) is essential to improve outcome, but poses a diagnostic challenge. Retinal vessels as an embryological part of the intracranial vasculature are easily accessible for analysis and may hold the key to a new and non-invasive monitoring technique. This investigation aims to determine the feasibility of standardized retinal vessel analysis (RVA) in the context of SAH. Methods In a prospective pilot study, we performed RVA in six patients awake and cooperative with SAH in the acute phase (day 2–14) and eight patients at the time of follow-up (mean 4.6±1.7months after SAH), and included 33 age-matched healthy controls. Data was acquired using a manoeuvrable Dynamic Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and neurovascular coupling. Results Image quality was satisfactory in the majority of cases (93.3%). In the acute phase after SAH, retinal arteries were significantly dilated when compared to the control group (124.2±4.3MU vs 110.9±11.4MU, p<0.01), a difference that persisted to a lesser extent in the later stage of the disease (122.7±17.2MU, p<0.05). Testing for neurovascular coupling showed a trend towards impaired primary vasodilation and secondary vasoconstriction (p = 0.08, p = 0.09 resp.) initially and partial recovery at the time of follow-up, indicating a relative improvement in a time-dependent fashion. Conclusion RVA is technically feasible in patients with SAH and can detect fluctuations in vessel diameter and autoregulation even in less severely affected patients. Preliminary data suggests potential for RVA as a new and non-invasive tool for advanced SAH monitoring, but clinical relevance and prognostic value will have to be determined in a larger cohort. Y1 - 2016 U6 - http://dx.doi.org/10.1371/journal.pone.0158781 SN - 1932-6203 VL - 11 IS - 7 PB - PLOS CY - San Francisco ER - TY - JOUR A1 - Handtke, Stefan A1 - Schroeter, Rebecca A1 - Jürgen, Britta A1 - Methling, Karen A1 - Schlüter, Rabea A1 - Albrecht, Dirk A1 - Hijum, Sacha A. F. T. van A1 - Bongaerts, Johannes A1 - Maurer, Karl-Heinz A1 - Lalk, Michael A1 - Schweder, Thomas A1 - Hecker, Michael A1 - Voigt, Birgit T1 - Bacillus pumilus reveals a remarkably high resistance to hydrogen peroxide provoked oxidative stress JF - PLOS one N2 - Bacillus pumilus is characterized by a higher oxidative stress resistance than other comparable industrially relevant Bacilli such as B. subtilis or B. licheniformis. In this study the response of B. pumilus to oxidative stress was investigated during a treatment with high concentrations of hydrogen peroxide at the proteome, transcriptome and metabolome level. Genes/proteins belonging to regulons, which are known to have important functions in the oxidative stress response of other organisms, were found to be upregulated, such as the Fur, Spx, SOS or CtsR regulon. Strikingly, parts of the fundamental PerR regulon responding to peroxide stress in B. subtilis are not encoded in the B. pumilus genome. Thus, B. pumilus misses the catalase KatA, the DNA-protection protein MrgA or the alkyl hydroperoxide reductase AhpCF. Data of this study suggests that the catalase KatX2 takes over the function of the missing KatA in the oxidative stress response of B. pumilus. The genome-wide expression analysis revealed an induction of bacillithiol (Cys-GlcN-malate, BSH) relevant genes. An analysis of the intracellular metabolites detected high intracellular levels of this protective metabolite, which indicates the importance of bacillithiol in the peroxide stress resistance of B. pumilus. Y1 - 2014 U6 - http://dx.doi.org/10.1371/journal.pone.0085625 SN - 1932-6203 VL - 9 IS - 1 PB - PLOS CY - San Francisco ER - TY - JOUR A1 - Almajhdi, Fahad N. A1 - Senger, Tilo A1 - Amer, Haitham M. A1 - Gissmann, Lutz A1 - Öhlschläger, Peter T1 - Design of a highly effective therapeutic HPV16 E6/E7-specific DNA vaccine: optimization by different ways of sequence rearrangements (Shuffling) JF - PLOS one N2 - Persistent infection with the high-risk Human Papillomavirus type 16 (HPV 16) is the causative event for the development of cervical cancer and other malignant tumors of the anogenital tract and of the head and neck. Despite many attempts to develop therapeutic vaccines no candidate has entered late clinical trials. An interesting approach is a DNA based vaccine encompassing the nucleotide sequence of the E6 and E7 viral oncoproteins. Because both proteins are consistently expressed in HPV infected cells they represent excellent targets for immune therapy. Here we report the development of 8 DNA vaccine candidates consisting of differently rearranged HPV-16 E6 and E7 sequences within one molecule providing all naturally occurring epitopes but supposedly lacking transforming activity. The HPV sequences were fused to the J-domain and the SV40 enhancer in order to increase immune responses. We demonstrate that one out of the 8 vaccine candidates induces very strong cellular E6- and E7- specific cellular immune responses in mice and, as shown in regression experiments, efficiently controls growth of HPV 16 positive syngeneic tumors. This data demonstrates the potential of this vaccine candidate to control persistent HPV 16 infection that may lead to malignant disease. It also suggests that different sequence rearrangements influence the immunogenecity by an as yet unknown mechanism. Y1 - 2014 U6 - http://dx.doi.org/10.1371/journal.pone.0113461 SN - 1932-6203 VL - 11 IS - 9 PB - PLOS CY - San Francisco ER - TY - JOUR A1 - Immel, Timo A. A1 - Groth, Ulrich A1 - Huhn, Thomas A1 - Öhlschläger, Peter T1 - Titanium salan complexes displays strong antitumor properties in vitro and in vivo in mice JF - PLoS ONE N2 - The anticancer activity of titanium complexes has been known since the groundbreaking studies of Köpf and Köpf-Maier on titanocen dichloride. Unfortunately, possibly due to their fast hydrolysis, derivatives of titanocen dichloride failed in clinical studies. Recently, the new family of titanium salan complexes containing tetradentate ONNO ligands with anti-cancer properties has been discovered. These salan complexes are much more stabile in aqueous media. In this study we describe the biological activity of two titanium salan complexes in a mouse model of cervical cancer. High efficiency of this promising complex family was demonstrated for the first time in vivo. From these data we conclude that titanium salan complexes display very strong antitumor properties exhibiting only minor side effects. Our results may influence the chemotherapy with metallo therapeutics in the future. Y1 - 2011 U6 - http://dx.doi.org/10.1371/journal.pone.0017869 VL - 6 IS - 3 PB - Plos CY - San Francisco, California, US ER -