PLD2 has both enzymatic and cell proliferation-inducing capabilities, that are differentially regulated by phosphorylation and dephosphorylation.

Phospholipase D2 (PLD2) overexpression in mammalian cells results in cell transformation. We have hypothesized that this is due to an increase of de novo DNA synthesis. We show here that overexpression of PLD2-WT leads to an increased DNA synthesis, as measured by the expression levels of the proliferation markers PCNA, p27(KIP1) and phospho-histone-3.

Maturational trajectories of cortical brain development through the pubertal transition: unique species and sex differences in the monkey revealed through structural magnetic resonance imaging.

Characterizing normal brain development in the rhesus macaque is a necessary prerequisite for establishing better nonhuman primate models of neuropathology. Structural magnetic resonance imaging scans were obtained on 37 rhesus monkeys (20 Male, 17 Female) between 10 and 64 months of age. Effects of age and sex were analyzed with a cross-sectional design.

Management of glioblastoma multiforme in HIV patients: a case series and review of published studies.

Aims: HIV infection is associated with an increased incidence of glioblastoma multiforme (GBM). Here we report four new cases of HIV-associated GBM, discuss these in the context of previously reported cases, and consider aspects of current glioma management in HIV-positive patients.

Methods And Results: Twenty-one cases of GBM in HIV-positive patients, including four treated recently at our own institution, are discussed.

Grandmother Co-Residence and School Enrollment in sub-Saharan Africa.

The HIV/AIDS pandemic in sub-Saharan Africa has brought renewed attention to the role of grandmothers as caregivers of children. Using 2004 DHS data, we examine the relationship between co-residence with a grandmother and child schooling in Lesotho, a country with one of the highest rates of HIV infection. Results confirm the critical role grandmothers play in the event of maternal death.

Quantitative PCR reveals transient and persistent algal viruses in Lake Ontario, Canada.

To determine if different algal viruses (Phycodnaviridae) share common patterns of seasonal abundance, quantitative PCR methods were developed and applied to monitor the abundances of three different viruses in Lake Ontario, Canada over 13 months. Throughout the year, the abundances of two different phycodnavirus polB gene fragments (LO1b-49 and LO1a-68) varied by more than two orders of magnitude, peaked during the autumn months, and were lowest during the summer. The seasonal abundance patterns of these two virus genes were similar and both were detected in almost every sample, but LO1b-49 was consistently an order of magnitude more abundant than LO1a-68.

Household Context and Subjective Well-Being Among the Oldest Old in China.

This article investigates the importance of household context to subjective well-being among the oldest old (aged 80 years and older) in China. Using data from the Chinese Longitudinal Healthy Longevity Survey, the authors find that living arrangements have strong implications for elderly emotional health. First, living alone is associated with lower subjective well-being.

The human ACC2 CT-domain C-terminus is required for full functionality and has a novel twist.

Inhibition of acetyl-CoA carboxylase (ACC) may prevent lipid-induced insulin resistance and type 2 diabetes, making the enzyme an attractive pharmaceutical target. Although the enzyme is highly conserved amongst animals, only the yeast enzyme structure is available for rational drug design. The use of biophysical assays has permitted the identification of a specific C-terminal truncation of the 826-residue human ACC2 carboxyl transferase (CT) domain that is both functionally competent to bind inhibitors and crystallizes in their presence.

Incontinent ileovesicostomy: Long-term outcomes and complications.

Aims: Incontinent ileovesicostomy was popularized in the mid-1990s as a surgical option for patients with neurogenic voiding dysfunction who lack the dexterity to perform clean catheterization. There are several case series in the literature, but few studies look at the long-term outcomes and complications associated with this procedure.

Methods: We review the outcomes of 12 patients who underwent incontinent ileovesicostomy for management of neurogenic voiding dysfunction since its introduction at our institution in 1998.

Transcriptional switch of dormant tumors to fast-growing angiogenic phenotype.

Tumor dormancy has important implications for early detection and treatment of cancer. Lack of experimental models and limited clinical accessibility constitute major obstacles to the molecular characterization of dormant tumors. We have developed models in which human tumors remain dormant for a prolonged period of time (>120 days) until they switch to rapid growth and become strongly angiogenic.

Chromatin condensation in terminally differentiating mouse erythroblasts does not involve special architectural proteins but depends on histone deacetylation.

Terminal erythroid differentiation in vertebrates is characterized by progressive heterochromatin formation and chromatin condensation and, in mammals, culminates in nuclear extrusion. To date, although mechanisms regulating avian erythroid chromatin condensation have been identified, little is known regarding this process during mammalian erythropoiesis. To elucidate the molecular basis for mammalian erythroblast chromatin condensation, we used Friend virus-infected murine spleen erythroblasts that undergo terminal differentiation in vitro.

Sub-acute blindness in a patient with a temporal lobe astrocytoma.

This report describes an unusual case of a middle-aged man who suffered sub-acute visual loss rendering him blind over a period of 4 weeks, associated with the diagnosis of a right temporal lobe World Health Organization grade 4 astrocytoma (glioblastoma multiforme). Chronic papilloedema had been diagnosed at presentation, and this persisted after his debulking surgery, but there was no radiological evidence of direct involvement (by compression or infiltration) of the visual pathways. This case report describes the sub-acute on chronic nature of his visual loss, and suggests possible causes and preventative measures for visual loss in these patients.

Accurate whole human genome sequencing using reversible terminator chemistry.

DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost.

Gene duplication, co-option and recruitment during the origin of the vertebrate brain from the invertebrate chordate brain.

The brain of the basal chordate amphioxus has been compared to the vertebrate diencephalic forebrain, midbrain, hindbrain and spinal cord on the basis of the cell architecture from serial electron micrographs and patterns of developmental gene expression. In addition, genes specifying the neural plate and neural plate border as well as Gbx and Otx, that position the midbrain/hindbrain boundary (MHB), are expressed in comparable patterns in amphioxus and vertebrates. However, migratory neural crest is lacking in amphioxus, and although it has homologs of the genes that specify neural crest, they are not expressed at the edges of the amphioxus neural plate.

Structural basis for the improved drug resistance profile of new generation benzophenone non-nucleoside HIV-1 reverse transcriptase inhibitors.

Owing to the emergence of resistant virus, next generation non-nucleoside HIV reverse transcriptase inhibitors (NNRTIs) with improved drug resistance profiles have been developed to treat HIV infection. Crystal structures of HIV-1 RT complexed with benzophenones optimized for inhibition of HIV mutants that were resistant to the prototype benzophenone GF128590 indicate factors contributing to the resilience of later compounds in the series (GW4511, GW678248). Meta-substituents on the benzophenone A-ring had the designed effect of inducing better contacts with the conserved W229 while reducing aromatic stacking interactions with the highly mutable Y181 side chain, which unexpectedly adopted a "down" position.

Short tail with skin lesion phenotype occurs in transgenic mice with keratin-14 promoter-directed expression of mutant CXCR2.

CXCR2 plays an important role during cutaneous wound healing. Transgenic mice were generated using the keratin-14 promoter/enhancer to direct expression of wild-type human CXCR2 (K14hCXCR2 WT) or mutant CXCR2, in which the carboxyl-terminal domain (CTD) was truncated at Ser 331 and the dileucine AP-2 binding motif was mutated to alanine (K14hCXCR2 331T/LL/AA/IL/AA). Our results indicate that K14hCXCR2WT transgenic mice exhibited a normal phenotype, while K14hCXCR2 331T/LL/AA/IL/AA transgenic mice were born with tails of normal length, but three to eight days after birth their tails degenerated, leaving only a short tail stub.

Process characterization of powder blending by near-infrared spectroscopy: blend end-points and beyond.

The purpose of this paper is to utilize near-infrared (NIR) spectroscopy to characterize powder blending in-line. A multivariate model-based approach was used to determine end-point and variability at the end-point of blending processes. Two monitoring positions for NIR spectrometers were evaluated; one was located on the top of the Bin-blender and the other was on the rotation axis.

The evolution of alternative splicing in the Pax family: the view from the Basal chordate amphioxus.

Pax genes encode transcription factors critical for metazoan development. Large-scale gene duplication with subsequent gene losses during vertebrate evolution has resulted in two human genes for each of the Pax1/9, Pax3/7, and Pax4/6 subfamilies and three for the Pax2/5/8 subfamily, compared to one each in the cephalochordate amphioxus. In addition, alternative splicing occurs in vertebrate Pax transcripts from all four subfamilies, and many splice forms are known to have functional importance.

The use of net analyte signal orthogonalization in the separation of multi-component diffraction patterns obtained from X-ray powder diffraction of intact compacts.

X-ray powder diffraction (XRPD) analysis of intact multi-component consolidated mixtures has significant potential owing to the ability to non-destructively quantify and discriminate between solid phases in composite bodies with minimal sample preparation. There are, however, limitations to the quantitative power using traditional univariate methods on diffraction data containing features from all components in the system. The ability to separate multi-component diffraction data into patterns representing single constituents allows both composition as well as physical phenomena associated with the individual components of complex systems to be probed.

Determination of figures of merit for near-infrared and Raman spectrometry by net analyte signal analysis for a 4-component solid dosage system.

Process analytical technology has elevated the role of sensors in pharmaceutical manufacturing. Often the ideal technology must be selected from many suitable candidates based on limited data. Net analyte signal (NAS) theory provides an effective platform for method characterization based on multivariate figures of merit (FOM).