Nanoscale structure of type I collagen fibrils: quantitative measurement of D-spacing.

This article details a quantitative method to measure the D-periodic spacing of type I collagen fibrils using atomic force microscopy coupled with analysis using a two-dimensional fast fourier transform approach. Instrument calibration, data sampling and data analysis are discussed and comparisons of the data to the complementary methods of electron microscopy and X-ray scattering are made. Examples of the application of this new approach to the analysis of type I collagen morphology in disease models of estrogen depletion and osteogenesis imperfecta (OI) are provided.

Striatal neuronal loss correlates with clinical motor impairment in Huntington's disease.

Huntington's disease (HD) is characterized clinically by chorea, motor impairment, psychiatric manifestations, and dementia. Atrophy of the striatum is the neuropathological hallmark of HD, and previous studies have suggested that striatal atrophy correlates more closely with motor impairment than with chorea. Motor impairment, as measured by motor impairment score, correlates with functional disability in HD patients, but chorea does not.

Molecular and morphologic correlates of the alternative lengthening of telomeres phenotype in high-grade astrocytomas.

Recent studies suggest that the telomere maintenance mechanism known as alternative lengthening of telomeres (ALT) is relatively more common in specific glioma subsets and strongly associated with ATRX mutations. We retrospectively examined 116 high-grade astrocytomas (32 pediatric glioblastomas, 65 adult glioblastomas, 19 anaplastic astrocytomas) with known ALT status using tissue microarrays to identify associations with molecular and phenotypic features. Immunohistochemistry was performed using antibodies against ATRX, DAXX, p53 and IDH1(R132H) mutant protein.

Expanded endonasal endoscopic approach for resection of a growth hormone-secreting pituitary macroadenoma coexistent with a cavernous carotid artery aneurysm.

The co-existence of pituitary adenomas (PA) and carotid artery aneurysms has been described and may be particularly frequent in acromegaly. The co-occurrence of an intracranial aneurysm in the setting of a PA presents significant risk to the patient, particularly when the aneurysm is within or near the operative field. We describe a 48-year-old, right-handed female patient with a large skull base lesion who had a left cavernous carotid artery aneurysm detected on her preoperative imaging studies.

Decreased 5-hydroxymethylcytosine is associated with neural progenitor phenotype in normal brain and shorter survival in malignant glioma.

Epigenetic modification of DNA by cytosine methylation to produce 5-methylcytosine (5mC) has become well-recognized as an important epigenetic process in human health and disease. Recently, further modification of 5mC by the ten eleven translocated (TET) family of enzymes to produce 5-hydroxymethylcytosine (5hmC) has been described. In the present study, we used immunohistochemistry to evaluate the distribution of 5hmC in human brain during different periods of development and in a large series of gliomas (n=225).

Activation of canonical WNT/β-catenin signaling enhances in vitro motility of glioblastoma cells by activation of ZEB1 and other activators of epithelial-to-mesenchymal transition.

Here we show that activation of the canonical WNT/β-catenin pathway increases the expression of stem cell genes and promotes the migratory and invasive capacity of glioblastoma. Modulation of WNT signaling alters the expression of epithelial-to-mesenchymal transition activators, suggesting a role of this process in the regulation of glioma motility. Using immunohistochemistry in patient-derived glioblastoma samples we showed higher numbers of cells with intranuclear signal for β-catenin in the infiltrating edge of tumor compared to central tumor parenchyma.

Yes-associated protein 1 is activated and functions as an oncogene in meningiomas.

The Hippo signaling pathway is functionally conserved in Drosophila melanogaster and mammals, and its proposed function is to control tissue homeostasis by regulating cell proliferation and apoptosis. The core components are composed of a kinase cascade that culminates with the phosphorylation and inhibition of Yes-associated protein 1 (YAP1). Phospho-YAP1 is retained in the cytoplasm.

Nature versus nurture in glioblastoma: microenvironment and genetics can both drive mesenchymal transcriptional signature.

This Commentary highlights the article by Cooper et al, which describes the association of mesenchymal glioblastoma with necrosis and poor prognosis, suggesting key signaling nodes for targeted therapies.

Estrogen depletion results in nanoscale morphology changes in dermal collagen.

Tissue cryo-sectioning combined with atomic force microscopy imaging reveals that the nanoscale morphology of dermal collagen fibrils, quantified using the metric of D-periodic spacing, changes under the condition of estrogen depletion. Specifically, a new subpopulation of fibrils with D-spacings in the region between 56 and 59 nm is present 2 years following ovariectomy in ovine dermal samples. In addition, the overall width of the distribution, both values above and below the mean, was found to be increased.

Suboccipital malignant solitary fibrous tumor: report of a case.

Solitary fibrous tumors (SFTs) are rare soft-tissue sarcomas usually arising in the pleura of the thoracic cavity. Thirty percent of SFTs present in extrapleural locations, and infrequently in the head and neck region. While the majority of SFTs are benign, aggressive variants have been described.

Neoplastic cells are a rare component in human glioblastoma microvasculature.

Microvascular proliferation is a key biological and diagnostic hallmark of human glioblastoma, one of the most aggressive forms of human cancer. It has recently been suggested that stem-like glioblastoma cells have the capacity to differentiate into functional endothelial cells, and that a significant proportion of the vascular lining in tumors has a neoplastic origin. In principle, this finding could significantly impact the efficacy and development of antiangiogenic therapies targeting the vasculature.

Establishment and characterization of a primary human chordoma xenograft model.

Object: Chordomas are rare tumors arising from remnants of the notochord. Because of the challenges in achieving a complete resection, the radioresistant nature of these tumors, and the lack of effective chemotherapeutics, the median survival for patients with chordomas is approximately 6 years. Reproducible preclinical model systems that closely mimic the original patient's tumor are essential for the development and evaluation of effective therapeutics.

Neuroendocrine carcinoma of the cervix during pregnancy: A case report.

► Neuroendocrine carcinoma of the cervix is a rare and aggressive malignancy. ► A multimodality approach must be individualized when diagnosed during pregnancy. ► We report the use of a therapeutic cervical cone and adjuvant chemotherapy.

Biophysical characterization of a riboflavin-conjugated dendrimer platform for targeted drug delivery.

The present study describes the biophysical characterization of generation-five poly(amidoamine) (PAMAM) dendrimers conjugated with riboflavin (RF) as a cancer-targeting platform. Two new series of dendrimers were designed, each presenting the riboflavin ligand attached at a different site (isoalloxazine at N-3 and d-ribose at N-10) and at varying ligand valency. Isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC) were used to determine the binding activity for riboflavin binding protein (RfBP) in a cell-free solution.

Primary intramedullary spinal germ cell tumors.

Background: Intramedullary spinal germ cell tumors are rare lesions, with germinomas being the most common variant.

Methods: To date, there have been 23 reports of primary intramedullary germ cell tumors described in the literature, the vast majority occurring in Japanese patients.

Results: We present a case of a nonmetastatic intramedullary germ cell tumor in a 28-year-old Caucasian woman.

Female soccer knee injury: observed knowledge gaps in injury prevention among players/parents/coaches and current evidence (the KNOW study).

This study sought to determine if knowledge regarding the risk for knee injuries and the potential for their prevention is being translated to female adolescent soccer players (13-18 years), their parents, and coaches. Eligible participants in the 2007 indoor soccer season were surveyed to determine their knowledge of the risk for and the potential to prevent knee injuries, and their knowledge of effective prevention strategies, if they felt that injury prevention was possible. Team selection was stratified to be representative of both competitive and recreational level play and age group distributions within the selected soccer association.

Restoring ecological integrity in highly regulated rivers: the role of baseline data and analytical references.

The goal of restoring ecological integrity in rivers is frequently accompanied by an assumption that a comparative reference reach can be identified to represent minimally impaired conditions. However, in many regulated rivers, no credible historical, morphological or process-based reference reach exists. Resilient restoration designs should instead be framed around naturalization, using multiple analytical references derived from empirically-calibrated field- and model-based techniques to develop an integrated ecological reference condition.

Identification of stromally expressed molecules in the prostate by tag-profiling of cancer-associated fibroblasts, normal fibroblasts and fetal prostate.

The stromal microenvironment has key roles in prostate development and cancer, and cancer-associated fibroblasts (CAFs) stimulate tumourigenesis via several mechanisms including the expression of pro-tumourigenic factors. Mesenchyme (embryonic stroma) controls prostate organogenesis, and in some circumstances can re-differentiate prostate tumours. We have applied next-generation Tag profiling to fetal human prostate, normal human prostate fibroblasts (NPFs) and CAFs to identify molecules expressed in prostatic stroma.

Bioanalytical Screening of Riboflavin Antagonists for Targeted Drug Delivery - A Thermodynamic and Kinetic Study.

The present study screened riboflavin mimicking small molecules to determine their binding activity for the riboflavin binding protein. We performed thermodynamic and kinetic binding studies of these molecules using a combination of two analytical approaches; isothermal titration calorimetry and surface plasmon resonance spectroscopy. Screening of a biased set of non-riboflavin based small molecules by microcalorimetry led to the discovery of two known drug molecules, quinacrine and chloroquine, as favorable ligands for the riboflavin receptor with K(D) value of 264, and 2100 nM, respectively.

Yes-associated protein 1 is widely expressed in human brain tumors and promotes glioblastoma growth.

The hippo pathway and its downstream mediator yes-associated protein 1 (YAP1) regulate mammalian organ size in part through modulating progenitor cell numbers. YAP1 has also been implicated as an oncogene in multiple human cancers. Currently, little is known about the expression of YAP1 either in normal human brain tissue or in central nervous system neoplasms.

Papillary tumor of the pineal region in a 15-month-old boy.

The papillary tumor of the pineal region (PTPR) is a distinct entity that is particularly rare in the pediatric population. The authors document the youngest reported patient with this clinicopathological entity to date. A case of PTPR in a 15-month-old boy is described.

Design, synthesis, and biological functionality of a dendrimer-based modular drug delivery platform.

A modular dendrimer-based drug delivery platform was designed to improve upon existing limitations in single dendrimer systems. Using this modular strategy, a biologically active platform containing receptor mediated targeting and fluorescence imaging modules was synthesized by coupling a folic acid (FA) conjugated dendrimer with a fluorescein isothiocyanate (FITC) conjugated dendrimer. The two different dendrimer modules were coupled via the 1,3-dipolar cycloaddition reaction ("click" chemistry) between an alkyne moiety on the surface of the first dendrimer and an azide moiety on the second dendrimer.

Effect of Mass Transport in the Synthesis of Partially Acetylated Dendrimer: Implications for Functional Ligand-Nanoparticle Distributions.

Partial acetylation of the amine-terminated poly(amidoamine) dendrimer has been used in the preparation of dendrimer particles conjugated with a wide variety of functional ligands including targeting moieties, therapeutic agents, and dye molecules. The effectiveness of mass transport during the partial acetylation reaction was found to have a major effect on subsequent distributions of dendrimer-ligand components and to be a major source of inconsistency between batches. This study has broad implications for a wide range of nanoparticle-ligand systems because it demonstrates that conjugates with the same mean ligand-particle ratios can have completely different distribution profiles.

Comparison of BD Bactec Plus blood culture media to VersaTREK Redox blood culture media for detection of bacterial pathogens in simulated adult blood cultures containing therapeutic concentrations of antibiotics.

Antibiotic neutralization in blood culture media from two automated systems was evaluated by measuring the recovery of organisms and times to detection in simulated cultures. Overall, BD Bactec Plus media (Bactec FX system) outperformed TREK 80 ml Redox media (VersaTREK system), although results suggest a relative rather than an absolute increased rate of recovery for the Bactec media.

Origin of broad polydispersion in functionalized dendrimers and its effects on cancer-cell binding affinity.

Nanoparticles with multiple ligands have been proposed for use in nanomedicine. The multiple targeting ligands on each nanoparticle can bind to several locations on a cell surface facilitating both drug targeting and uptake. Experiments show that the distribution of conjugated ligands is unexpectedly broad, and the desorption rate appears to depend exponentially upon the mean number of attached ligands.