The role of dorsomedial striatum adenosine 2A receptors in the loss of goal-directed behaviour.

Rationale: Adenosine A receptors (AR) in the dorsal striatum have been implicated in goal-directed behaviour. While activation of these receptors with several methods has resulted in an insensitivity to outcome devaluation, particular explanations for how they disrupt behaviour have not been explored. We both confirm a role for A receptors in goal-directed responding and evaluate additional behavioural aspects of goal-directed control to more fully understand the role of A receptors in instrumental behaviour.

Bisphenol A Exposure Induces Sensory Processing Deficits in Larval Zebrafish during Neurodevelopment.

Because of their development, relatively simple nervous system, translucency, and availability of tools to investigate neural function, larval zebrafish are an exceptional model for understanding neurodevelopmental disorders and the consequences of environmental toxins. Furthermore, early in development, zebrafish larvae easily absorb chemicals from water, a significant advantage over methods required to expose developing organisms to chemical agents Bisphenol A (BPA) and BPA analogs are ubiquitous environmental toxins with known molecular consequences. All humans have measurable quantities of BPA in their bodies.

Induction of Short-Term Sensitization by an Aversive Chemical Stimulus in Zebrafish Larvae.

Larval zebrafish possess a number of molecular and genetic advantages for rigorous biological analyses of learning and memory. These advantages have motivated the search for novel forms of memory in these animals that can be exploited for understanding the cellular and molecular bases of vertebrate memory formation and consolidation. Here, we report a new form of behavioral sensitization in zebrafish larvae that is elicited by an aversive chemical stimulus [allyl isothiocyanate (AITC)] and that persists for ≥30 min.

A Congenital High Flow Arteriovenous Malformation of the Bladder Presenting With Polypoid Cystitis and Ureteral Obstruction.

A 21-year-old male with a history of Down's syndrome presented with hematuria and right flank pain. Computed Tomography (CT) of the abdomen/pelvis revealed right hydronephrosis and a right-sided pelvic vascular abnormality. Angiography revealed an arteriovenous malformation (AVM) fed by the right superior and inferior vesical arteries and nephrostogram showed a long segment of obstructed distal right ureter.

Prostate cancer trends in Barbados: An analysis of the Barbados Urologic Diseases Survey database.

Objectives: To describe the burden and trend of prostate cancer (CaP) in the Caribbean island of Barbados.

Methods: All urologic pathology reports in Barbados between 1990 and 2009 were entered into the Barbados Urologic Diseases Survey (BUDS) database. All new cases of CaP were identified and the database was used to assess trends in CaP epidemiology over the study period.

Robotic-Assisted Renal Surgery.

Background: Minimally invasive surgical techniques have revolutionized the surgical management of kidney cancer. Current evidence suggests that the surgical developments gained by traditional laparoscopy have been advanced by the robotic platform, particularly as it has been applied to techniques for nephron preservation.

Methods: The medical literature from peer-reviewed journals was reviewed to evaluate the feasibility and efficacy of robotic-assisted surgery in the management of renal cell carcinoma.

Excision and Patch Grafting of a Lateral Peyronie's Plaque-Utilizing a Longitudinal "Window" Approach.

Introduction: Peyronie's disease (PD) is a debilitating disorder in which collagen deposition, fibrosis, and plaques in the tunica albuginea result in penile curvature, shortening, and pain. For severe curvatures requiring plaque incision or excision with grafting (PIEG), a subcoronal circumcising incision with penile degloving has historically been used.

Aims: The aim of this study was to report our unique approach to PIEG via a longitudinal "window" incision for the correction of PD, minimizing the surgical manipulation and dissection accompanying the traditional circumcising incisional approach that may lead to increased postoperative edema, pain, and prolonged healing time.

An extramedullary plasmacytoma in the testicle: A case report and review of the literature.

We present a rare case of testicular extramedullary plasmacytoma (EMP) in a 43-year-old man with multiple myeloma and diffuse systemic involvement refractory to chemotherapy. Multiple myeloma is typically found within the bone marrow and rarely involves other organs and sites. EMPs are most frequently associated with the head and neck region, but in rare cases testicular involvement have been seen.

Intravesical lipiodol injection technique for image-guided radiation therapy for bladder cancer.

Introduction: To describe the technique of injecting Lipiodol in the submucosa of the urinary bladder wall as a novel modality to improve localization of muscle-invasive bladder tumors before image-guided radiation therapy.

Technical Considerations: Eight patients underwent submucosal Lipiodol injections at transurethral bladder tumor reresection. A rigid cystoscope with a working port was used to inject Lipiodol into bladder submucosa circumferentially around the tumor bed (2-3 mm from margin of resection).

A large cellular angiofibroma of the male pelvis presenting with obstructive voiding: A case report and review of the literature.

Cellular angiofibromas (CAF) are rare, benign soft-tissue tumours. The diagnosis of CAF is important given the heavy resemblance to other tumours. Herein, we describe a case of a rapidly growing, very large (13.

Atomic structure of the nuclear pore complex targeting domain of a Nup116 homologue from the yeast, Candida glabrata.

The nuclear pore complex (NPC), embedded in the nuclear envelope, is a large, dynamic molecular assembly that facilitates exchange of macromolecules between the nucleus and the cytoplasm. The yeast NPC is an eightfold symmetric annular structure composed of ~456 polypeptide chains contributed by ~30 distinct proteins termed nucleoporins. Nup116, identified only in fungi, plays a central role in both protein import and mRNA export through the NPC.

Structure of the C-terminal domain of Saccharomyces cerevisiae Nup133, a component of the nuclear pore complex.

Nuclear pore complexes (NPCs), responsible for the nucleo-cytoplasmic exchange of proteins and nucleic acids, are dynamic macromolecular assemblies forming an eight-fold symmetric co-axial ring structure. Yeast () NPCs are made up of at least 456 polypeptide chains of ~30 distinct sequences. Many of these components (nucleoporins, Nups) share similar structural motifs and form stable subcomplexes.

Structure of a putative BenF-like porin from Pseudomonas fluorescens Pf-5 at 2.6 A resolution.

The X-ray structure of a putative BenF-like (gene name: PFL1329) protein from (PflBenF) has been determined at 2.6Å resolution. X-ray crystallography revealed a canonical 18-stranded β-barrel fold that forms a central pore with a diameter of ∼4.

Structures of PHR domains from Mus musculus Phr1 (Mycbp2) explain the loss-of-function mutation (Gly1092-->Glu) of the C. elegans ortholog RPM-1.

PHR [PAM (protein associated with Myc)-HIW (Highwire)-RPM-1 (regulator of presynaptic morphology 1)] proteins are conserved, large multi-domain E3 ubiquitin ligases with modular architecture. PHR proteins presynaptically control synaptic growth and axon guidance and postsynaptically regulate endocytosis of glutamate receptors. Dysfunction of neuronal ubiquitin-mediated proteasomal degradation is implicated in various neurodegenerative diseases.

Effect of Sch 55700, a humanized monoclonal antibody to human interleukin-5, on eosinophilic responses and bronchial hyperreactivity.

This report describes the development and the biology of Sch 55700, a humanized monoclonal antibody to human IL-5 (hIL-5). Sch 55700 was synthesized using CDR (complementarity determining regions) grafting technology by incorporating the antigen recognition sites for hIL-5 onto consensus regions of a human IgG4 framework. In vitro, Sch 55700 displays high affinity (Kd = 20 pmol/l) binding to hIL-5, inhibits the binding of hIL-5 to Ba/F3 cells (IC50 = 0.

The human homologue of Saccharomyces cerevisiae Gle1p is required for poly(A)+ RNA export.

The mechanism of mRNA export is a complex issue central to cellular physiology. We characterized previously yeast Gle1p, a protein with a leucine-rich (LR) nuclear export sequence (NES) that is essential for poly(A)+ RNA export in Saccharomyces cerevisiae. To characterize elements of the vertebrate mRNA export pathway, we identified a human homologue of yeast Gle1p and analyzed its function in mammalian cells.

Defining the essential functional regions of the nucleoporin Nup145p.

Studies of the essential nucleoporin Nup145p have shown that its depletion is coincident with a block in RNA export and that deletion of its amino-terminal domain results in clustering of nuclear pore complexes. To further define the functional domains of Nup145p, we have characterized a panel of nup145 mutants. Deletions from both the amino terminus and the carboxy terminus resulted in temperature sensitive mutants that accumulated polyadenylated RNA in the nucleus at the non-permissive temperature.

The N-terminal end of the CH2 domain of chimeric human IgG1 anti-HLA-DR is necessary for C1q, Fc gamma RI and Fc gamma RIII binding.

We have found that amino acid residues necessary for C1q and Fc gamma R binding of human IgG1 are located in the N-terminal region of the CH2 domain, residues 231-238, using a matched set of engineered antibodies based on the anti-HLA-DR antibody L243. Changing the leucine 235 in the CH2 region of IgG3 and IgG4 to glutamic acid was already known to abolish Fc gamma RI binding. We have confirmed this for IgG1 and also found a concomitant abolition of human complement lysis with retention of Fc gamma RIII-mediated function.

Differential effect of isotype on efficacy of anti-tumor necrosis factor alpha chimeric antibodies in experimental septic shock.

Immune complexes containing human gamma (g)1 or murine g2a antibodies generate secondary effector mechanisms via Fc receptor binding or complement activation, whereas those containing human g4 or murine g1 antibodies generally do not. Therefore, isotype selection of therapeutic antibodies may have important clinical consequences. In a rabbit model of human tumor necrosis factor (rhuTNF)-induced pyrexia, a murine/human chimeric g4 anti-human TNF-alpha monoclonal antibody (mAb) (cCB0011) showed a dose-dependent inhibition of pyrexia, whereas a g1 isotype variant of the same mAb gave a marked pyrexia that was seen at all doses indicative of an immune complex-mediated response.