136 research outputs found

    Training in Counseling Psychology: An Introduction to the Major Contribution

    Get PDF
    Abstract This Major Contribution, consisting of four articles, critically evaluates the status of training in counseling psychology, especially at the entry level, and offers a model for moving the field forward. In this first article, we provide a rationale for the contribution, laying the foundation for the subsequent three articles. Specifically, we ask the questions, Do training programs in counseling psychology produce the desired results? and Is the prevailing paradigm of training effective in developing counselor competence? Then we report on the research showing a disappointing relationship among training, experience, and expertise. We conclude by inviting the profession to engage in honest self-reflection about the status and future direction of training in counseling psychology

    Aster Models with Random Effects via Penalized Likelihood

    Get PDF
    1 online resource (PDF, 61 pages

    What goes in does not always come out: The impact of the ruminant digestive system of sheep on plant material, and its importance for the interpretation of dung-derived archaeobotanical assemblages

    Get PDF
    On archaeological sites where livestock dung was a major fuel source, plant material that survives digestion intact may well be preserved in the remnants of dung-fuelled fires. Preserved plant remains which were derived from dung relate to the diet of animals, and thus provide a way of investigating the agro-pastoral economies of the past. In order to improve our understanding of the taphonomic processes to which plant material is exposed to during digestion, we applied archaeobotanical methods to the analysis of dung from sheep fed a known diet of cereal and wild plant material. Two clear patterns emerge from these investigations. First, cereal material (grain or chaff) survives digestion poorly and was rarely found in the dung analysed. Second, large proportions of seeds of various wild species survive digestion in an identifiable form, probably due to their small size and/or protective coating. These findings are crucial for reliable interpretation of dung-derived plant material in archaeological settings

    Anti-nicastrin monoclonal antibodies elicit pleiotropic anti-tumour pharmacological effects in invasive breast cancer cells

    Get PDF
    The goal of targeted cancer therapies is to specifically block oncogenic signalling, thus maximising efficacy, while reducing side-effects to patients. The gamma-secretase (GS) complex is an attractive therapeutic target in haematological malignancies and solid tumours with major pharmaceutical activity to identify optimal inhibitors. Within GS, nicastrin (NCSTN) offers an opportunity for therapeutic intervention using blocking monoclonal antibodies (mAbs). Here we explore the role of anti-nicastrin monoclonal antibodies, which we have developed as specific, multi-faceted inhibitors of proliferation and invasive traits of triple-negative breast cancer cells. We use 3D in vitro proliferation and invasion assays as well as an orthotopic and tail vail injection triple-negative breast cancer in vivo xenograft model systems. RNAScope assessed nicastrin in patient samples. Anti-NCSTN mAb clone-2H6 demonstrated a superior anti-tumour efficacy than clone-10C11 and the RO4929097 small molecule GS inhibitor, acting by inhibiting GS enzymatic activity and Notch signalling in vitro and in vivo. Confirming clinical relevance of nicastrin as a target, we report evidence of increased NCSTN mRNA levels by RNA in situ hybridization (RNAScope) in a large cohort of oestrogen receptor negative breast cancers, conferring independent prognostic significance for disease-free survival, in multivariate analysis. We demonstrate here that targeting NCSTN using specific mAbs may represent a novel mode of treatment for invasive triple-negative breast cancer, for which there are few targeted therapeutic options. Furthermore, we propose that measuring NCSTN in patient samples using RNAScope technology may serve as companion diagnostic for anti-NCSTN therapy in the clinic

    The Importance of Tree Size and Fecundity for Wind Dispersal of Big-Leaf Mahogany

    Get PDF
    Seed dispersal by wind is a critical yet poorly understood process in tropical forest trees. How tree size and fecundity affect this process at the population level remains largely unknown because of insufficient replication across adults. We measured seed dispersal by the endangered neotropical timber species big-leaf mahogany (Swietenia macrophylla King, Meliaceae) in the Brazilian Amazon at 25 relatively isolated trees using multiple 1-m wide belt transects extended 100 m downwind. Tree diameter and fecundity correlated positively with increased seed shadow extent; but in combination large, high fecundity trees contributed disproportionately to longer-distance dispersal events (>60 m). Among three empirical models fitted to seed density vs. distance in one dimension, the Student-t (2Dt) generally fit best (compared to the negative exponential and inverse power). When seedfall downwind was modelled in two dimensions using a normalised sample, it peaked furthest downwind (c. 25 m) for large, high-fecundity trees; with the inverse Gaussian and Weibull functions providing comparable fits that were slightly better than the lognormal. Although most seeds fell within 30 m of parent trees, relatively few juveniles were found within this distance, resulting in juvenile-to-seed ratios peaking at c. 35–45 m. Using the 2Dt model fits to predict seed densities downwind, coupled with known fecundity data for 2000–2009, we evaluated potential Swietenia regeneration near adults (≤30 m dispersal) and beyond 30 m. Mean seed arrival into canopy gaps >30 m downwind was more than 3× greater for large, high fecundity trees than small, high-fecundity trees. Tree seed production did not necessarily scale up proportionately with diameter, and was not consistent across years, and this resulting intraspecific variation can have important consequences for local patterns of dispersal in forests. Our results have important implications for management and conservation of big-leaf mahogany populations, and may apply to other threatened wind-dispersed Meliaceae trees

    Charting Evolution’s Trajectory: Using Molluscan Eye Diversity to Understand Parallel and Convergent Evolution

    Get PDF
    For over 100 years, molluscan eyes have been used as an example of convergent evolution and, more recently, as a textbook example of stepwise evolution of a complex lens eye via natural selection. Yet, little is known about the underlying mechanisms that create the eye and generate different morphologies. Assessing molluscan eye diversity and understanding how this diversity came about will be important to developing meaningful interpretations of evolutionary processes. This paper provides an introduction to the myriad of eye types found in molluscs, focusing on some of the more unusual structures. We discuss how molluscan eyes can be applied to the study of evolution by examining patterns of convergent and parallel evolution and provide several examples, including the putative convergence of the camera-type eyes of cephalopods and vertebrates

    Paxillin Mediates Sensing of Physical Cues and Regulates Directional Cell Motility by Controlling Lamellipodia Positioning

    Get PDF
    Physical interactions between cells and the extracellular matrix (ECM) guide directional migration by spatially controlling where cells form focal adhesions (FAs), which in turn regulate the extension of motile processes. Here we show that physical control of directional migration requires the FA scaffold protein paxillin. Using single-cell sized ECM islands to constrain cell shape, we found that fibroblasts cultured on square islands preferentially activated Rac and extended lamellipodia from corner, rather than side regions after 30 min stimulation with PDGF, but that cells lacking paxillin failed to restrict Rac activity to corners and formed small lamellipodia along their entire peripheries. This spatial preference was preceded by non-spatially constrained formation of both dorsal and lateral membrane ruffles from 5–10 min. Expression of paxillin N-terminal (paxN) or C-terminal (paxC) truncation mutants produced opposite, but complementary, effects on lamellipodia formation. Surprisingly, pax−/− and paxN cells also formed more circular dorsal ruffles (CDRs) than pax+ cells, while paxC cells formed fewer CDRs and extended larger lamellipodia even in the absence of PDGF. In a two-dimensional (2D) wound assay, pax−/− cells migrated at similar speeds to controls but lost directional persistence. Directional motility was rescued by expressing full-length paxillin or the N-terminus alone, but paxN cells migrated more slowly. In contrast, pax−/− and paxN cells exhibited increased migration in a three-dimensional (3D) invasion assay, with paxN cells invading Matrigel even in the absence of PDGF. These studies indicate that paxillin integrates physical and chemical motility signals by spatially constraining where cells will form motile processes, and thereby regulates directional migration both in 2D and 3D. These findings also suggest that CDRs may correspond to invasive protrusions that drive cell migration through 3D extracellular matrices
    corecore