New and Notable This Week

This week’s selection of recently published papers from MDPI journals.


Bioceramics for Hip Joints: The Physical Chemistry Viewpoint

Giuseppe Pezzotti 1,2,3,4

1Ceramic Physics Laboratory, Kyoto Institute of Technology, Sakyo-ku, Matsugasaki, Kyoto 606-8126, Japan, 2Department of Orthopedic Research, Loma Linda University, 11406 Loma Linda Drive, Suite 606 Loma Linda, CA 92354, USA, 3The Center for Advanced Medical Engineering and Informatics, Osaka University, Yamadaoka, Suita, Osaka 565-0871, Japan,4Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, 465 Kajii-cho, Kawaramachi dori, Kyoto 602-0841, Japan

Abstract: Which intrinsic biomaterial parameter governs and, if quantitatively monitored, could reveal to us the actual lifetime potential of advanced hip joint bearing materials? An answer to this crucial question is searched for in this paper, which identifies ceramic bearings as the most innovative biomaterials in hip arthroplasty. It is shown that, if in vivo exposures comparable to human lifetimes are actually searched for, then fundamental issues should lie in the physical chemistry aspects of biomaterial surfaces. Besides searching for improvements in the phenomenological response of biomaterials to engineering protocols, hip joint components should also be designed to satisfy precise stability requirements in the stoichiometric behavior of their surfaces when exposed to extreme chemical and micromechanical conditions. New spectroscopic protocols have enabled us to visualize surface stoichiometry at the molecular scale, which is shown to be the key for assessing bioceramics with elongated lifetimes with respect to the primitive alumina biomaterials used in the past.


For Open Access Article, see: Pezzotti, G. Bioceramics for Hip Joints: The Physical Chemistry ViewpointMaterials 20147, 4367-4410.



SUMOylation of FOXM1B Alters Its Transcriptional Activity on Regulation of MiR-200 Family and JNK1 in MCF7 Human Breast Cancer Cells

Chiung-Min Wang 1, Runhua Liu 2, Lizhong Wang 2, Leticia Nascimento 1, Victoria C. Brennan 1 and Wei-Hsiung Yang 1

1Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA 31404, USA, 2Department of Genetics and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA

Abstract: Transcription factor Forkhead Box Protein M1 (FOXM1) is a well-known master regulator in controlling cell-cycle pathways essential for DNA replication and mitosis, as well as cell proliferation. Among the three major isoforms of FOXM1, FOXM1B is highly associated with tumor growth and metastasis. The activities of FOXM1B are modulated by post-translational modifications (PTMs), such as phosphorylation, but whether it is modified by small ubiquitin-related modifier (SUMO) remains unknown. The aim of the current study was to determine whether FOXM1B is post-translationally modified by SUMO proteins and also to identify SUMOylation of FOXM1B on its target gene transcription activity. Here we report that FOXM1B is clearly defined as a SUMO target protein at the cellular levels. Moreover, a SUMOylation protease, SENP2, significantly decreased SUMOylation of FOXM1B. Notably, FOXM1B is selectively SUMOylated at lysine residue 463. While SUMOylation of FOXM1B is required for full repression of its target genes MiR-200b/c and p21, SUMOylation of FOXM1B is essential for full activation of JNK1 gene. Overall, we provide evidence that FOXM1B is post-translationally modified by SUMO and SUMOylation of FOXM1B plays a functional role in regulation of its target gene activities.


For Open Access Article, see: Wang, C.-M.; Liu, R.; Wang, L.; Nascimento, L.; Brennan, V.C.; Yang, W.-H. SUMOylation of FOXM1B Alters Its Transcriptional Activity on Regulation of MiR-200 Family and JNK1 in MCF7 Human Breast Cancer CellsInt. J. Mol. Sci. 201415, 10233-10251.



Therapeutic Vaccine Strategies against Human Papillomavirus

Hadeel Khallouf, Agnieszka K. Grabowska and Angelika B. Riemer 

Immunotherapy and -prevention, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany

Abstract: High-risk types of human papillomavirus (HPV) cause over 500,000 cervical, anogenital and oropharyngeal cancer cases per year. The transforming potential of HPVs is mediated by viral oncoproteins. These are essential for the induction and maintenance of the malignant phenotype. Thus, HPV-mediated malignancies pose the unique opportunity in cancer vaccination to target immunologically foreign epitopes. Therapeutic HPV vaccination is therefore an ideal scenario for proof-of-concept studies of cancer immunotherapy. This is reflected by the fact that a multitude of approaches has been utilized in therapeutic HPV vaccination design: protein and peptide vaccination, DNA vaccination, nanoparticle- and cell-based vaccines, and live viral and bacterial vectors. This review provides a comprehensive overview of completed and ongoing clinical trials in therapeutic HPV vaccination (summarized in tables), and also highlights selected promising preclinical studies. Special emphasis is given to adjuvant science and the potential impact of novel developments in vaccinology research, such as combination therapies to overcome tumor immune suppression, the use of novel materials and mouse models, as well as systems vaccinology and immunogenetics approaches.

For Open Access Article, see: Khallouf, H.; Grabowska, A.K.; Riemer, A.B. Therapeutic Vaccine Strategies against Human PapillomavirusVaccines 20142, 422-462.



Controversies Surrounding Clostridium difficile Infection in Infants and Young Children

Maribeth R. Nicholson 1, Isaac P. Thomsen 2 and Kathryn M. Edwards 3

1Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Vanderbilt University School of Medicine, 2200 Children’s Way, Nashville TN 37232, USA, 2Division of Pediatric Infectious Disease, Vanderbilt Vaccine Research Program, Vanderbilt University School of Medicine, 2200 Children’s Way, Nashville, TN 37232, USA, 3Division of Pediatric Infectious Disease, Vanderbilt Vaccine Research Program, Vanderbilt University School of Medicine, 2200 Children’s Way, Nashville, TN 37232, USA

Abstract: Clostridium difficile is a frequent cause of antibiotic-associated diarrhea in adults and older children. However, as many as 80% of infants can be asymptomatically colonized. The reasons for this have not been well established but are believed to be due to differences in toxin receptors or toxin internalization. Determining which children who test positive for C. difficile warrant treatment is exceedingly difficult, especially in the setting of increased rates of detection and the rising risk of disease in children lacking classic risk factors for C. difficile.

For Open Access Article, see: Nicholson, M.R.; Thomsen, I.P.; Edwards, K.M. Controversies Surrounding Clostridium difficile Infection in Infants and Young ChildrenChildren 20141, 40-47.


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The Cytolethal Distending Toxin Effects on Mammalian Cells: A DNA Damage Perspective

Elisabeth Bezine 1,2,3, Julien Vignard 1,2 and Gladys Mirey 1,2,4

1INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, F-31027 Toulouse, France,2Genotoxicity Signaling Team, Toxalim INRA, 180 Chemin de Tournefeuille BP 93173, F-31027 Toulouse, France,3Université de Toulouse, INP, UMR1331, Toxalim, F-31000 Toulouse, France, 4Université de Toulouse, UPS, UMR1331, Toxalim , F-31062 Toulouse, France

Abstract: The cytolethal distending toxin (CDT) is produced by many pathogenic Gram-negative bacteria and is considered as a virulence factor. In human cells, CDT exposure leads to a unique cytotoxicity associated with a characteristic cell distension and induces a cell cycle arrest dependent on the DNA damage response (DDR) triggered by DNA double-strand breaks (DSBs). CDT has thus been classified as a cyclomodulin and a genotoxin. Whereas unrepaired damage can lead to cell death, effective, but improper repair may be detrimental. Indeed, improper repair of DNA damage may allow cells to resume the cell cycle and induce genetic instability, a hallmark in cancer. In vivo, CDT has been shown to induce the development of dysplastic nodules and to lead to genetic instability, defining CDT as a potential carcinogen. It is therefore important to characterize the outcome of the CDT-induced DNA damage and the consequences for intoxicated cells and organisms. Here, we review the latest results regarding the host cell response to CDT intoxication and focus on DNA damage characteristics, cell cycle modulation and cell outcomes.


For Open Access Article, see: Bezine, E.; Vignard, J.; Mirey, G. The Cytolethal Distending Toxin Effects on Mammalian Cells: A DNA Damage PerspectiveCells 20143, 592-615.