Dip-pen nanolithography was used to construct arrays of proteins with 100- to 350-nanometer features. These nanoarrays exhibit almost no detectable nonspecific binding of proteins to their passivated portions even in complex mixtures of proteins, and therefore provide the opportunity to study a variety of surface-mediated biological recognition processes. For example, reactions involving the protein features and antigens in complex solutions can be screened easily by atomic force microscopy. As further proof-of-concept, these arrays were used to study cellular adhesion at the submicrometer scale.
Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of existing screening programs using HPV-based technology, 3) extension of adapted screening programs to developing populations, and 4) consideration of the broader spectrum of cancers and other diseases preventable by HPV vaccination in women, as well as in men. Despite the huge advances already achieved, there must be ongoing efforts including international advocacy to achieve widespread—optimally universal—implementation of HPV prevention strategies in both developed and developing countries. This article summarizes information from the chapters presented in a special ICO Monograph ‘Comprehensive Control of HPV Infections and Related Diseases’ Vaccine Volume 30, Supplement 5, 2012. Additional details on each subtopic and full information regarding the supporting literature references may be found in the original chapters.
Two series of redox-active, iron−sulfur core dendrimers of the general structure (nBu4N)2[Fe4S4(S-Dend)4] (Dend = dendrons of generations 1 through 4) were prepared. Heterogeneous electron-transfer rate constants indicated that the rigid series of dendrimers were more effective at attenuating the rate of electron transfer than were the flexible series of dendrimers. These results were rationalized using computationally derived models which indicated an offset and mobile iron−sulfur core in the flexible series of molecules and a more central and relatively immobile iron−sulfur core in the rigid series of molecules. Further consideration of these data indicated that, while the dendrimers containing rigid ligands had better encapsulated redox cores for a given molecular weight, these molecules had higher electron-transfer rates for a given molecular radius.
Previous studies have noted the presence of mesenchymal stem cells located within the connective tissue matrices of avian skeletal muscle, dermis, and heart. In these studies, clonal analysis coupled with dexamethasone treatment revealed the presence of multiple populations of stem cells composed of both lineagecommitted progenitor mesenchymal stem cells and lineage-uncommitted pluripotent mesenchyma1 stem cells. The present study was undertaken to assess the distribution of these stem cells in the connective tissues throughout various regions of the body. Day 11 chick embryos were divided into 26 separate regions. Heart, limb skeletal muscle, and limb dermis were included as control tissues. Cells were harvested enzymatically and grown using conditions optimal for the isolation, cryopreservation, and propagation of avian mesenchymal stem cells. Cell aliquots were plated, incubated with various concentrations of dexamethasone, and examined for differentiated phenotypes. Four recurring phenotypes appeared in dexamethasone-treated stem cells: skeletal muscle myotubes, fat cells, cartilage nodules, and bone nodules. These results suggest that progenitor mesenchymal stem cells and putative pluripotent mesenchymal stem cells with the potential to form at least four tissues of mesodermal origin have a widespread distribution throughout the body, being located within the connective tissue compartments of many organs and organ systems.
This paper presents a flexible approach for using Dip Pen Nanolithography (DPN) to nanopattern mixed monolayers for the selective immobilization of bioassemblies. DPN was used with a binary inksconsisting of a symmetric 11-mercaptoundecyl-penta(ethylene glycol) disulfide and a mixed disulfide substituted with one maleimide groupsto pattern nanoscale features that present functional groups for the chemospecific immobilization of cysteine-labeled biomolecules. This strategy was applied to the chemospecific immobilization of cysteine mutant cowpea mosaic virus capsid particles (cys-VCPs). The combination of DPN for defining nanopatterns and surface chemistries for controlling the immobilization of ligands will be broadly useful in basic and applied biology.
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