Derivation of pre-X inactivation human embryonic stem cells under physiological oxygen concentrations.

The presence of two active X chromosomes (XaXa) is a hallmark of the ground state of pluripotency specific to murine embryonic stem cells (ESCs). Human ESCs (hESCs) invariably exhibit signs of X chromosome inactivation (XCI) and are considered developmentally more advanced than their murine counterparts. We describe the establishment of XaXa hESCs derived under physiological oxygen concentrations.

CRX is a diagnostic marker of retinal and pineal lineage tumors.

Background: CRX is a homeobox transcription factor whose expression and function is critical to maintain retinal and pineal lineage cells and their progenitors. To determine the biologic and diagnostic potential of CRX in human tumors of the retina and pineal, we examined its expression in multiple settings.

Methodology/principal Findings: Using situ hybridization and immunohistochemistry we show that Crx RNA and protein expression are exquisitely lineage restricted to retinal and pineal cells during normal mouse and human development.

Profiling critical cancer gene mutations in clinical tumor samples.

Background: Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting.

Methodology: We developed and implemented an optimized mutation profiling platform ("OncoMap") to interrogate approximately 400 mutations in 33 known oncogenes and tumor suppressors, many of which are known to predict response or resistance to targeted therapies.

Rapid selection of cyclic peptides that reduce alpha-synuclein toxicity in yeast and animal models.

Phage display has demonstrated the utility of cyclic peptides as general protein ligands but cannot access proteins inside eukaryotic cells. Expanding a new chemical genetics tool, we describe the first expressed library of head-to-tail cyclic peptides in yeast (Saccharomyces cerevisiae). We applied the library to selections in a yeast model of alpha-synuclein toxicity that recapitulates much of the cellular pathology of Parkinson's disease.

Phase II study of protracted daily temozolomide for low-grade gliomas in adults.

Purpose: Resistance to temozolomide chemotherapy is partly mediated by O(6)-methylguanine-DNA methlytransferase (MGMT). Protracted treatment with temozolomide potentially overcomes MGMT resistance and improves outcome. We conducted a phase II study of protracted daily temozolomide in adults with low-grade gliomas.

Concentrated sodium chloride brine solutions as an additional treatment for preventing the introduction of nonindigenous species in the ballast tanks of ships declaring no ballast on board.

Currently, seawater flushing is the only management strategy for reducing the number of viable organisms in residual sediments and water of ballast tanks of vessels declaring no ballast on board (NOBOB) that traffic ports of the eastern United States. Previously, we identified several species of freshwater and brackish-water peracarid crustaceans able to survive the osmotic shock that occurs during open-ocean ballast water exchange and, potentially, to disperse over long distances via ballasted ships and NOBOB vessels. We tested the efficacy of concentrated sodium chloride brine solutions as an additional treatment for eradicating the halotolerant taxa often present in the ballast tanks of NOBOB ships.

Evolutionary and structural diversification of the larval nervous system among marine bryozoans.

Regardless of the morphological divergence among larval forms of marine bryozoans, the larval nervous system and its major effector organs (musculature and ciliary fields) are largely molded on the basis of functional demands of feeding, ciliary propulsion, phototactic behaviors, and substrate exploration. Previously published ultrastructural information and immunohistochemical reconstructions presented here indicate that neuronal pathways are largely ipsilateral, with more complex synaptic connections localized within the nerve nodule. Multiciliated sensory-motor neurons diversify structurally and functionally on the basis of their position along the axis of swimming largely due to the functional demands of photoklinotaxis and substrate exploration.

Tyrosine hydroxylase deficiency presenting with a biphasic clinical course.

Tyrosine hydroxylase deficiency, a cause of the autosomal recessive form of L-DOPA responsive dystonia, has been associated with a broad spectrum of movement disorders and clinical courses. We describe a new patient presenting with an early onset spastic paraplegia who later developed a progressive generalized dystonic-dyskinetic syndrome. He markedly improved with a very low dosage of L-DOPA/carbidopa, while higher dosages were not tolerated.

The morphology and evolutionary significance of the ciliary fields and musculature among marine bryozoan larvae.

Despite the embryological and anatomical disparities present among lophotrochozoan phyla, there are morphological similarities in the cellular arrangements of ciliated cells used for propulsion among the nonfeeding larval forms of kamptozoans, nemerteans, annelids, mollusks, and bryozoans. Evaluating whether these similarities are the result of convergent selective pressures or a shared (deep) evolutionary history is hindered by the paucity of detailed cellular information from multiple systematic groups from lesser-known, and perhaps, basal evolutionary phyla such as the Bryozoa. Here, I compare the ciliary fields and musculature among the major morphological grades of marine bryozoan larvae using light microscopy, SEM, and confocal imaging techniques.

Embryonic stem cell transcription factor signatures in the diagnosis of primary and metastatic germ cell tumors.

The core embryonic stem cell transcription factors (TFs) OCT3/4 (OCT4), NANOG, and SOX2 have shared as well as nonoverlapping roles in stem cell growth and differentiation. These same TFs are also expressed in various types of human germ cell tumors (GCTs), implicating them in regulation of tumor growth and differentiation. Although NANOG and OCT3/4 are sensitive and specific markers for seminoma and embryonal carcinoma, neither factor aids in the clinically important distinction of seminomatous from nonseminomatous tumors.

What is metamorphosis?

Metamorphosis (Gr. meta- "change" + morphe "form") as a biological process is generally attributed to a subset of animals: most famously insects and amphibians, but some fish and many marine invertebrates as well. We held a symposium at the 2006 Society for Integrative and Comparative Biology (SICB) annual meeting in Orlando, FL (USA) to discuss metamorphosis in a comparative context.

Comparative analysis of germ cell transcription factors in CNS germinoma reveals diagnostic utility of NANOG.

The homeodomain transcription factor, NANOG, along with OCT3/4 (POU5F1) and SOX2, is part of the core set of transcription factors that maintain embryonic stem cell self-renewal and pluripotency. Expression of NANOG has been detected in fetal germ cells and in gonadal germ cell tumors. To assess the diagnostic utility of NANOG in central nervous system (CNS) germ cell tumors, we analyzed its expression by immunohistochemistry in a series of 12 CNS germinomas and compared its expression with other stem cell markers.

Intramedullary neuroma of the cervicomedullary junction. Case report.

Neuromas typically arise in the peripheral nervous system in response to traumatic injury at the site of partial or complete nerve transection as new axons from the proximal nerve stump sprout to reinnervate the distal segment. In rare cases neuromas have also been described as intramedullary spinal cord lesions. These lesions have been identified as incidental autopsy findings in association with prior trauma and cervical spondylosis, multiple sclerosis, spinal tumors, and syringomyelia.

Quantitative determination of guanidinoacetate and creatine in dried blood spot by flow injection analysis-electrospray tandem mass spectrometry.

Background: Guanidinoacetate (GAA) and creatine (Cr) are reliable biochemical markers of primary creatine disorders. The aim of this study was to develop and validate a method for the determination of GAA and Cr in dried blood spot through the use of stable isotope dilution and flow injection analysis (FIA)-ESI-MS/MS.

Methods: Dried blood spots were extracted using methanol-water solution containing D3-Cr.

A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas.

Pheochromocytomas are neural crest-derived tumors that arise from inherited or sporadic mutations in at least six independent genes. The proteins encoded by these multiple genes regulate distinct functions. We show here a functional link between tumors with VHL mutations and those with disruption of the genes encoding for succinate dehydrogenase (SDH) subunits B (SDHB) and D (SDHD).

A waterborne behavioral cue for the actinotroch larva of Phoronis pallida (Phoronida) produced by Upogebia pugettensis (Decapoda: Thalassinidea).

Phoronis pallida (Phoronida) occurs as a commensal within the burrow of Upogebia pugettensis (Decapoda: Thalassinidea). Upogebia-conditioned seawater (UCSW) induced an exploratory swimming behavior in competent larvae of P. pallida in a dosage-dependent manner.

JAGGED1 expression is associated with prostate cancer metastasis and recurrence.

Recent studies suggest that NOTCH signaling can promote epithelial-mesenchymal transitions and augment signaling through AKT, an important growth and survival pathway in epithelial cells and prostate cancer in particular. Here we show that JAGGED1, a NOTCH receptor ligand, is significantly more highly expressed in metastatic prostate cancer as compared with localized prostate cancer or benign prostatic tissues, based on immunohistochemical analysis of JAGGED1 expression in human tumor samples from 154 men. Furthermore, high JAGGED1 expression in a subset of clinically localized tumors was significantly associated with recurrence, independent of other clinical parameters.

Larval development of Phoronis pallida (Phoronida): implications for morphological convergence and divergence among larval body plans.

Morphological variation among larval body plans must be placed into a phylogenetic and ecological context to assess whether similar morphologies are the result of phylogenetic constraints or convergent selective pressures. Investigations are needed of the diverse larval forms within the Lophotrochozoa, especially the larvae of phoronids and brachiopods. The actinotroch larva of Phoronis pallida (Phoronida) was reared in the laboratory to metamorphic competence.

Comparison of the neuromuscular systems among actinotroch larvae: systematic and evolutionary implications.

A comparative analysis of the larval and presumptive juvenile neuromuscular systems among actinotroch larvae was performed using confocal laser microscopy with probes for F-actin and serotonin. Currently, there are two main categories of larval nervous systems based on the origin of the nerve fibers that innervate the larval tentacles. Characteristics of the serotonergic cells of the larval apical ganglion and juvenile nervous system have remained relatively conserved, but the structure of the secondary (hood) sense organ and the juvenile tentacles has diversified among species.

Structure and metamorphic remodeling of the larval nervous system and musculature of Phoronis pallida (Phoronida).

The structure of the larval nervous system and the musculature of Phoronis pallida were studied, as well as the remodeling of these systems at metamorphosis. The serotonergic portion of the apical ganglion is a U-shaped field of cell bodies that send projections into a central neuropil. The majority of the serotonergic cells are (at least) bipolar sensory cells, and a few are nonsensory cells.

FokI requires two specific DNA sites for cleavage.

FokI is a bipartite restriction endonuclease that recognizes a non-palindromic DNA sequence, and then makes double-stranded cuts outside of that sequence to leave a 5' overhang. Earlier kinetic and crystallographic studies suggested that FokI might function as a dimer. Here, we show, using dynamic light-scattering, gel-filtration and analytical ultracentrifugation, that FokI dimerizes only in the presence of divalent metal ions.