Behavioral evidence that repetitive responses in a Free-Movement Pattern Y-maze are associated with ageing-related deficit in working memory.

Visuospatial working memory (VSWM) is crucial for navigating complex environments and is known to decline with ageing. The Free-Movement Pattern (FMP) Y-maze, used in animal studies, provides a robust paradigm for assessing VSWM via analyses of individual differences in repeated alternating sequences of left (L) and right (R) responses (LRLR, etc.), the predominant search pattern in many species.

Benefits of nostalgic landmarks for people living with Alzheimer's disease.

Background: Emerging literature shows that nostalgia induced by autobiographical reflection and music confers psychological benefits to people living with dementia.

Objective: Our objective was to test the potential benefits of nostalgic landmarks for people living with Alzheimer's disease.

Methods: We displayed the landmarks as wall-mounted pictures within a virtual environment.

Nostalgia enhances route learning in a virtual environment.

Salient landmarks enhance route learning. We hypothesised that semantically salient nostalgic landmarks would improve route learning compared to non-nostalgic landmarks. In two experiments, participants learned a route through a computer-generated maze using directional arrows and wall-mounted pictures.

Induction of spatial anxiety in a virtual navigation environment.

Spatial anxiety (i.e., feelings of apprehension and fear about navigating everyday environments) can adversely impact people's ability to reach desired locations and explore unfamiliar places.

YAP vs. TAZ: differences in expression revealed through rigorous validation of target-specific monoclonal antibodies.

The ability to reproduce scientific findings is foundational in research; yet, it is compromised in part by poorly characterized reagents, including antibodies. In this report, we describe the application of complementary validation strategies tailored for use in immunohistochemical assays in the characterization of rabbit monoclonal antibodies against YAP and TAZ, homologous and sequentially similar transcriptional effectors of the Hippo signaling pathway. A lack of antibody reagents rigorously validated for immunohistochemistry has limited the Hippo signaling research community's ability to interrogate YAP and TAZ independently in tissue.

ERK2 Phosphorylates PFAS to Mediate Posttranslational Control of De Novo Purine Synthesis.

The RAS-ERK/MAPK (RAS-extracellular signal-regulated kinase/mitogen-activated protein kinase) pathway integrates growth-promoting signals to stimulate cell growth and proliferation, at least in part, through alterations in metabolic gene expression. However, examples of direct and rapid regulation of the metabolic pathways by the RAS-ERK pathway remain elusive. We find that physiological and oncogenic ERK signaling activation leads to acute metabolic flux stimulation through the de novo purine synthesis pathway, thereby increasing building block availability for RNA and DNA synthesis, which is required for cell growth and proliferation.

Phospho-proteomic discovery of novel signal transducers including thioredoxin-interacting protein as mediators of erythropoietin-dependent human erythropoiesis.

Erythroid cell formation critically depends on signals transduced via erythropoietin (EPO)/EPO receptor (EPOR)/JAK2 complexes. This includes not only core response modules (e.g.

Suppression of early hematogenous dissemination of human breast cancer cells to bone marrow by retinoic Acid-induced 2.

Unlabelled: Regulatory pathways that drive early hematogenous dissemination of tumor cells are insufficiently defined. Here, we used the presence of disseminated tumor cells (DTC) in the bone marrow to define patients with early disseminated breast cancer and identified low retinoic acid-induced 2 (RAI2) expression to be significantly associated with DTC status. Low RAI2 expression was also shown to be an independent poor prognostic factor in 10 different cancer datasets.

The Notch1 transcriptional activation domain is required for development and reveals a novel role for Notch1 signaling in fetal hematopoietic stem cells.

Notch1 is required to generate the earliest embryonic hematopoietic stem cells (HSCs); however since Notch-deficient embryos die early in gestation, additional functions for Notch in embryonic HSC biology have not been described. We used two complementary genetic models to address this important biological question. Unlike Notch1-deficient mice, mice lacking the conserved Notch1 transcriptional activation domain (TAD) show attenuated Notch1 function in vivo and survive until late gestation, succumbing to multiple cardiac abnormalities.

A transgenic zebrafish model of targeted oocyte ablation and de novo oogenesis.

We describe here a novel transgenic zebrafish, Tg(zpc:G4VP16/UAS:nfsB-mCherry) that effectively demonstrates the targeted oocyte ablation in the adult zebrafish ovary. This transgenic line expresses bacterial nitroreductase enzyme (nfsB) under the control of the oocyte-specific zona pellucida C (zpc) gene promoter. Adult transgenic females exposed to the prodrug metronidazole demonstrated near-complete ablation of growing oocytes, resulting in ovarian degeneration and complete cessation of reproductive function.

cables1 is required for embryonic neural development: molecular, cellular, and behavioral evidence from the zebrafish.

In vitro studies have suggested that the Cables1 gene regulates epithelial cell proliferation, whereas other studies suggest a role in promoting neural differentiation. In efforts to clarify the functions of Cables1 in vivo, we conducted gain- and loss-of-function studies targeting its ortholog (cables1) in the zebrafish embryo. Similar to rodents, zebrafish cables1 mRNA expression is detected most robustly in embryonic neural tissues.

Targeted gene knockdown in zebrafish reveals distinct intraembryonic functions for insulin-like growth factor II signaling.

IGF-II is the predominant IGF ligand regulating prenatal growth in all vertebrates, including humans, but its central role in placental development has confounded efforts to fully elucidate its functions within the embryo. Here we use a nonplacental model vertebrate (zebrafish) to interrogate the intraembryonic functions of IGF-II signaling. The zebrafish genome contains two coorthologs of mammalian IGF2 (igf2a, igf2b), which exhibit distinct patterns of expression during embryogenesis.

Paracrine insulin-like growth factor signaling influences primordial germ cell migration: in vivo evidence from the zebrafish model.

IGF signaling has been shown to stimulate migration of multiple cell types in vitro, but few studies have confirmed an equivalent function for IGF signaling in vivo. We recently showed that suppression of IGF receptors in the zebrafish embryo disrupts primordial germ cell (PGC) migration, but the mechanism underlying these effects has not been elucidated. We hypothesized that PGCs are intrinsically dependent upon IGF signaling during the migratory phase of development.

Mechanisms of Cables 1 gene inactivation in human ovarian cancer development.

Cables 1, a cyclin-dependent kinase binding protein, is primarily involved in cell cycle regulation. Loss of nuclear Cables 1 expression is observed in human colon, lung and endometrial cancers. We previously reported that loss of nuclear Cables 1 expression was also observed with high frequency in a limited sample set of human ovarian carcinomas, although the mechanisms underlying loss of nuclear Cables 1 expression remained unknown.

Insulin-like growth factor receptor 1b is required for zebrafish primordial germ cell migration and survival.

Insulin-like growth factor (IGF) signaling is a critical regulator of somatic growth during fetal and adult development, primarily through its stimulatory effects on cell proliferation and survival. IGF signaling is also required for development of the reproductive system, although its precise role in this regard remains unclear. We have hypothesized that IGF signaling is required for embryonic germline development, which requires the specification and proliferation of primordial germ cells (PGCs) in an extragonadal location, followed by directed migration to the genital ridges.

Insulin-like growth factor signaling in fish.

The insulin-like growth factor (IGF) system plays a central role in the neuroendocrine regulation of growth in all vertebrates. Evidence from studies in a variety of vertebrate species suggest that this growth factor complex, composed of ligands, receptors, and high-affinity binding proteins, evolved early during vertebrate evolution. Among nonmammalian vertebrates, IGF signaling has been studied most extensively in fish, particularly teleosts of commercial importance.

Targeted knockdown of insulin-like growth factor binding protein-2 disrupts cardiovascular development in zebrafish embryos.

IGF binding protein-2 (IGFBP-2) is an evolutionarily conserved protein that binds IGFs and modulates their biological activities. Although the actions of IGFBP-2 have been well studied in vitro, we have a poor understanding of its in vivo functions, particularly during early development. Using the transparent zebrafish embryo as a model, we show that IGFBP-2 mRNA is expressed in lens epithelium and cranial boundary regions during early embryonic development and becomes localized to the liver by the completion of embryogenesis.

Thyroglobulin type-1 domain protease inhibitors exhibit specific expression in the cortical ooplasm of vitellogenic rainbow trout oocytes.

The synthesis, uptake, and processing of yolk proteins remain poorly described aspects of oviparous reproductive development. In this study, we report the identification and characterization of two protease inhibitors in rainbow trout ovary whose expression and distribution are directly associated with yolk protein uptake in vitellogenic oocytes. The first transcript, termed "oocyte protease inhibitor-1" (OPI-1), is predicted to encode a 9.

Yolk proteolysis in rainbow trout oocytes after serum-free culture: evidence for a novel biochemical mechanism of atresia in oviparous vertebrates.

Our recent studies show little evidence for increased granulosa cell apoptosis during atresia in teleost follicles, in direct contrast to the mammalian model. Histological evidence suggests that atresia in many oviparous vertebrates involves proteolytic degradation of the energy-rich yolk storage proteins within the oocyte. This study tests the hypothesis that physiological conditions that promote atresia (hormone withdrawal) lead to increased lysosomal protease activity in rainbow trout oocytes.

Inhibition of apoptosis in vitellogenic ovarian follicles of rainbow trout (Oncorhynchus mykiss) by salmon gonadotropin, epidermal growth factor, and 17beta-estradiol.

We have examined the ability of selected hormones and growth factors to suppress the spontaneous onset on apoptotic DNA fragmentation in isolated vitellogenic rainbow trout ovarian follicles cultured in serum-free conditions. Primary culture of isolated follicles for 24 hr in serum-free conditions resulted in a 3-5-fold increase in the amount of fragmented DNA as compared to non-cultured controls, measured by radioactive 3'end-labeling. Culture in medium containing salmon gonadotropin (SG-G100; 1, 5 microg/ml) suppressed the spontaneous onset of DNA fragmentation in dose-dependent fashion.