Structure and Function of the Stigma in Relation to the Germinative Requirements of the Pollen in the Easter Lily

Stigma of Easter Lily is papillate. Over the surface of the papillae a mucilaginous layer is formed and from this mucilaginous layer the pollen absorbs the requisite amount of water for germination. The papillae and nearly all cells of the stigma previous to the opening of the flower contain much starch which is transported from cell to cell chiefly in the form of dextrin. As the starch disappears in the papillae the mucilage appears on the outside of their walls. The pollen germinates on almost any media or in almost any solution that furnishes the required amount of water

Neocuproine-functionalized silica-coated magnetic nanoparticles for extraction of copper(II) from aqueous solution

Neocuproine has been covalently bound to silica-coated maghemite(c-Fe2O3) magnetic nanoparticles (MNPs) by a phenyl ether linkage. The resulting MNPs are able to remove Cu(II) from 12 ppm aqueous solution with an extraction efficiency of up to 99% at pH 2

An Approach to Nonparametric Inference on the Causal Dose Response Function

The causal dose response curve is commonly selected as the statistical parameter of interest in studies where the goal is to understand the effect of a continuous exposure on an outcome.Most of the available methodology for statistical inference on the dose-response function in the continuous exposure setting requires strong parametric assumptions on the probability distribution. Such parametric assumptions are typically untenable in practice and lead to invalid inference. It is often preferable to instead use nonparametric methods for inference, which only make mild assumptions about the data-generating mechanism. We propose a nonparametric test of the null hypothesis that the dose-response function is equal to a constant function. We argue that when the null hypothesis holds, the dose-response function has zero variance. Thus, one can test the null hypothesis by assessing whether there is sufficient evidence to claim that the variance is positive. We construct a novel estimator for the variance of the dose-response function, for which we can fully characterize the null limiting distribution and thus perform well-calibrated tests of the null hypothesis. We also present an approach for constructing simultaneous confidence bands for the dose-response function by inverting our proposed hypothesis test. We assess the validity of our proposal in a simulation study. In a data example, we study, in a population of patients who have initiated treatment for HIV, how the distance required to travel to an HIV clinic affects retention in care.Comment: 39 pages, 5 figure

Lysophosphatidic acid receptor 1 inhibition:a potential treatment target for pulmonary fibrosis

Lysophosphatidic acid (LPA)-mediated activation of LPA receptor 1 (LPAR1) contributes to the pathophysiology of fibrotic diseases such as idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc). These diseases are associated with high morbidity and mortality despite current treatment options. The LPA-producing enzyme autotaxin (ATX) and LPAR1 activation contribute to inflammation and mechanisms underlying fibrosis in preclinical fibrotic models. Additionally, elevated levels of LPA have been detected in bronchoalveolar lavage fluid from patients with IPF and in serum from patients with SSc. Thus, ATX and LPAR1 have gained considerable interest as pharmaceutical targets to combat fibrotic disease and inhibitors of these targets have been investigated in clinical trials for IPF and SSc. The goals of this review are to summarise the current literature on ATX and LPAR1 signalling in pulmonary fibrosis and to help differentiate the novel inhibitors in development. The mechanisms of action of ATX and LPAR1 inhibitors are described and preclinical studies and clinical trials of these agents are outlined. Because of their contribution to numerous physiologic events underlying fibrotic disease, ATX and LPAR1 inhibition presents a promising therapeutic strategy for IPF, SSc and other fibrotic diseases that may fulfil unmet needs of the current standard of care.</p

Lysophosphatidic acid receptor 1 inhibition:a potential treatment target for pulmonary fibrosis

Lysophosphatidic acid (LPA)-mediated activation of LPA receptor 1 (LPAR1) contributes to the pathophysiology of fibrotic diseases such as idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc). These diseases are associated with high morbidity and mortality despite current treatment options. The LPA-producing enzyme autotaxin (ATX) and LPAR1 activation contribute to inflammation and mechanisms underlying fibrosis in preclinical fibrotic models. Additionally, elevated levels of LPA have been detected in bronchoalveolar lavage fluid from patients with IPF and in serum from patients with SSc. Thus, ATX and LPAR1 have gained considerable interest as pharmaceutical targets to combat fibrotic disease and inhibitors of these targets have been investigated in clinical trials for IPF and SSc. The goals of this review are to summarise the current literature on ATX and LPAR1 signalling in pulmonary fibrosis and to help differentiate the novel inhibitors in development. The mechanisms of action of ATX and LPAR1 inhibitors are described and preclinical studies and clinical trials of these agents are outlined. Because of their contribution to numerous physiologic events underlying fibrotic disease, ATX and LPAR1 inhibition presents a promising therapeutic strategy for IPF, SSc and other fibrotic diseases that may fulfil unmet needs of the current standard of care.</p

VAMP8 is a vesicle SNARE that regulates mucin secretion in airway goblet cells

Mucin secretion in the lung is regulated by the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) exocytotic core, which has not been defined in airway goblet cells. In this study, the SNARE vesicle-associated membrane protein 8 (VAMP8) was found to be expressed in human airway epithelial goblet cells. VAMP8 knockdown by RNA interference techniques reduced airway epithelial mucin secretion induced by PAR agonists, neutrophil elastase and ATP. Basal (non-agonist elicited) mucin secretion was also reduced as a result of VAMP8 knockdown. Importantly, mucin secretion was reduced in the lungs of VAMP8 knockout mice compared to wild-type littermates. Our data suggest that VAMP8 is an essential SNARE in airway mucin granule exocytosis. Reduction of VAMP8 activity/expression may provide a novel therapeutic target to ameliorate airway mucus obstruction in lung diseases

Engaging rural preceptors in new longitudinal community clerkships during workforce shortage: a qualitative study

Background: In keeping with its mission to produce doctors for rural and regional Australia, the University of Wollongong, Graduate School of Medicine has established an innovative model of clinical education. This includes a 12-month integrated community-based clerkship in a regional or rural setting, offering senior students longitudinal participation in a \u27community of practice\u27 with access to continuity of patient care experiences, continuity of supervision and curriculum, and individualised personal and professional development. This required developing new teaching sites, based on attracting preceptors and providing them with educational and physical infrastructure. A major challenge was severe health workforce shortages. Methods: Before the new clerkship started, we interviewed 28 general practitioners to determine why they engaged as clerkship preceptors. Independent researchers conducted semi-structured interviews. Responses were transcribed for inductive qualitative content analysis. Results: The new model motivated preceptors to engage because it enhanced their opportunities to contribute to authentic learning when compared with the perceived limitations of short-term attachments. Preceptors appreciated the significant recognition of the value of general practice teaching and the honour of major involvement in the university. They predicted that the initiative would have positive effects on general practitioner morale and improve the quality of their practice. Other themes included the doctors\u27 commitment to their profession, \u27handing on\u27 to the next generation and helping their community to attract doctors in the future. Conclusions: Supervisors perceive that new models of clinical education offer alternative solutions to health care education, delivery and workforce. The longitudinal relationship between preceptor, student and community was seen as offering reciprocal benefits. General practitioners are committed to refining practice and ensuring generation of new members in their profession. They are motivated to engage in novel regional and rural longitudinal clinical clerkships as they perceive that they offer students an authentic learning experience and are a potential strategy to help address workforce shortages and maldistribution

Structure-activity relationship studies of tetrahydroquinolone free fatty acid receptor 3 modulators

Free fatty acid receptor 3 (FFA3, previously GPR41) is activated by short-chain fatty acids, mediates health effects of the gut microbiota, and is a therapeutic target for metabolic and inflammatory diseases. The shortage of well-characterized tool compounds has however impeded progress. Herein, we report structure–activity relationship of an allosteric modulator series and characterization of physicochemical and pharmacokinetic properties of selected compounds, including previous and new tools. Two representatives, 57 (TUG-1907) and 63 (TUG-2015), showed improved solubility and preserved potency. Of these, 57, with EC50 = 145 nM and a solubility of 33 μM, showed high clearance in vivo but is a preferred tool in vitro. In contrast, 63, with EC50 = 162 nM and a solubility of 9 μM, showed lower clearance and seems better suited for in vivo studies. Using 57, we demonstrate for the first time that FFA3 activation leads to calcium mobilization in murine dorsal root ganglia

Centromere Protein B Null Mice are Mitotically and Meiotically Normal but Have Lower Body and Testis Weights

CENP-B is a constitutive centromere DNA-binding protein that is conserved in a number of mammalian species and in yeast. Despite this conservation, earlier cytological and indirect experimental studies have provided conflicting evidence concerning the role of this protein in mitosis. The requirement of this protein in meiosis has also not previously been described. To resolve these uncertainties, we used targeted disruption of the Cenpb gene in mouse to study the functional significance of this protein in mitosis and meiosis. Male and female Cenpb null mice have normal body weights at birth and at weaning, but these subsequently lag behind those of the heterozygous and wild-type animals. The weight and sperm content of the testes of Cenpb null mice are also significantly decreased. Otherwise, the animals appear developmentally and reproductively normal. Cytogenetic fluorescence-activated cell sorting and histological analyses of somatic and germline tissues revealed no abnormality. These results indicate that Cenpb is not essential for mitosis or meiosis, although the observed weight reduction raises the possibility that Cenpb deficiency may subtly affect some aspects of centromere assembly and function, and result in reduced rate of cell cycle progression, efficiency of microtubule capture, and/or chromosome movement. A model for a functional redundancy of this protein is presented

Filling Key Gaps in Population and Community Ecology

We propose research to fill key gaps in the areas of population and community ecology, based on a National Science Foundation workshop identifying funding priorities for the next 5–10 years. Our vision for the near future of ecology focuses on three core areas: predicting the strength and context-dependence of species interactions across multiple scales; identifying the importance of feedbacks from individual interactions to ecosystem dynamics; and linking pattern with process to understand species coexistence. We outline a combination of theory development and explicit, realistic tests of hypotheses needed to advance population and community ecology