Adenomatous Polyposis Coli is Present Near the Minimal Level Required for Accurate Graded Responses to the Wingless Morphogen

The mechanisms by which the Wingless (Wg) morphogen modulates the activity of the transcriptional activator Armadillo (Arm) to elicit precise, concentration-dependent cellular responses remain uncertain. Arm is targeted for proteolysis by the Axin/Adenomatous polyposis coli (Apc1 and Apc2)/Zeste-white 3 destruction complex, and Wg-dependent inactivation of destruction complex activity is crucial to trigger Arm signaling. In the prevailing model for Wg transduction, only Axin levels limit destruction complex activity, whereas Apc is present in vast excess. To test this model, we reduced Apc activity to different degrees, and analyzed the effects on three concentration-dependent responses to Arm signaling that specify distinct retinal photoreceptor fates. We find that both Apc1 and Apc2 negatively regulate Arm activity in photoreceptors, but that the relative contribution of Apc1 is much greater than that of Apc2. Unexpectedly, a less than twofold reduction in total Apc activity, achieved by loss of Apc2, decreases the effective threshold at which Wg elicits a cellular response, thereby resulting in ectopic responses that are spatially restricted to regions with low Wg concentration. We conclude that Apc activity is not present in vast excess, but instead is near the minimal level required for accurate graded responses to the Wg morphogen

Thidiazuron como indutor de embriogênese somática em café (Coffea canephora Pierre).

Os efeitos de thidiazuron (TDZ) na indução de embriogênese somática em Coffea canephora foi investigado. Explantes foliares de C. canephora foram cultivados em um meio de cultura suplementado com diferentes concentrações de TDZ. Embriões somáticos foram observados nas concentrações de 0,25 até 2 mM, após dois meses em cultivo. Dentre os tratamentos testados, TDZ a 1 mM mostrou a mais alta freqüência de explantes com regeneração e maior número de embriões por explante. Entretanto, a indução de embriogênese somática ocorreu de forma não-sincronizada com todos os tratamentos investigados apresentando embriões em diferentes estádios de desenvolvimento

Evidence for Tankyrases as Antineoplastic Targets in Lung Cancer

Background: New pharmacologic targets are urgently needed to treat or prevent lung cancer, the most common cause of cancer death for men and women. This study identified one such target. This is the canonical Wnt signaling pathway, which is deregulated in cancers, including those lacking adenomatous polyposis coli or β -catenin mutations. Two poly-ADP-ribose polymerase (PARP) enzymes regulate canonical Wnt activity: tankyrase (TNKS) 1 and TNKS2. These enzymes poly-ADP-ribosylate (PARsylate) and destabilize axin, a key component of the β -catenin phosphorylation complex. Methods: This study used comprehensive gene profiles to uncover deregulation of the Wnt pathway in murine transgenic and human lung cancers, relative to normal lung. Antineoplastic consequences of genetic and pharmacologic targeting of TNKS in murine and human lung cancer cell lines were explored, and validated in vivo in mice by implantation of murine transgenic lung cancer cells engineered with reduced TNKS expression relative to controls. Results: Microarray analyses comparing Wnt pathway members in malignant versus normal tissues of a murine transgenic cyclin E lung cancer model revealed deregulation of Wnt pathway components, including TNKS1 and TNKS2. Real-time PCR assays independently confirmed these results in paired normal-malignant murine and human lung tissues. Individual treatments of a panel of human and murine lung cancer cell lines with the TNKS inhibitors XAV939 and IWR-1 dose-dependently repressed cell growth and increased cellular axin 1 and tankyrase levels. These inhibitors also repressed expression of a Wnt-responsive luciferase construct, implicating the Wnt pathway in conferring these antineoplastic effects. Individual or combined knockdown of TNKS1 and TNKS2 with siRNAs or shRNAs reduced lung cancer cell growth, stabilized axin, and repressed tumor formation in murine xenograft and syngeneic lung cancer models. Conclusions: Findings reported here uncovered deregulation of specific components of the Wnt pathway in both human and murine lung cancer models. Repressing TNKS activity through either genetic or pharmacological approaches antagonized canonical Wnt signaling, reduced murine and human lung cancer cell line growth, and decreased tumor formation in mouse models. Taken together, these findings implicate the use of TNKS inhibitors to target the Wnt pathway to combat lung cancer

Assessment of Automobiles and Pedestrians Control Techniques Within Markets in Kaduna State, Nigeria

The Assessment of automobile and pedestrian control techniques within the market environment cannot be overemphasized as it is one of the most important ways in curtailing poor market environment in terms of traffic congestion. Automobile and pedestrian congestion is a situation that arises when the road networks are incapable of accommodating the traffic generated. Automobile and pedestrians control techniques in market refers to regulation, adoption, or maintenance of automobile and pedestrian functions or feature either by design or new construction within the market. The sustainable design encompasses standard layout, adequate parking, standard road network system, provision of signs and markings, proper zoning etc. This research aimed at assessing pedestrian and automobile control technique adopted within markets in Kaduna with the view of designing a more improved circulation pattern and sustainable markets in terms of automobile and pedestrian control within the study area. With this regard, an observation method of research was adopted. The daily markets were randomly selected out of the numerous markets within Kaduna metropolis and its environs. The result shows that the proper automobiles and pedestrians control techniques was not properly observed or  adopted in over 90% of the market. The study further revealed that the selected markets within Kaduna share similar features and characteristics. Therefore to curtail these, recommendations were made on various practical methods for integration/adoption in market design so as to archive an effective automobile control within the markets in Kaduna metropolis. Keywords: Automobiles, Control Techniques, Market Congestion, Pedestria

Extraction and Characterization of Microplastics from Organic Solid Matrices and their Remediation

Plastics have become an essential commodity due to their superior engineering properties, durability and low cost to be used by a wide range of commercial products. However, the degradation of plastics due to mechanical, chemical, biological, and photolytic stresses has led to the formation of microplastics (MPs). MPs have risen to the top of environmental concerns due to their affinity to pollute the environment, and to pass to the food chain, threatening human health. In this context, attempts have been made to extract and characterize MPs from aqueous and solid matrices. A problem that not only hampers research but also regulatory decisions is the variety of methods used for the extraction and characterization of MPs, especially in organic solid matrices (OSMs) with organic (OM) \u3e 5%, making the comparison of results difficult. This paper aims to address this need, by critically assessing the methodologies and protocols used for extraction of MPs from OSMs, which includes sample collection, dispersion, OM removal, and separation, as well as the qualitative and quantitative characterization of MPs. Further, current impediments in the accurate characterization of MPs are identified along with recommendations for future developments. Finally, recent efforts by various countries to legislate against certain sources of MPs, as well as issues and novel techniques to remediate MPs from the soil, and wastewater have been highlighted

The E3 ubiquitin ligase component, Cereblon, is an evolutionarily conserved regulator of Wnt signaling

Immunomodulatory drugs (IMiDs) are important for the treatment of multiple myeloma and myelodysplastic syndrome. Binding of IMiDs to Cereblon (CRBN), the substrate receptor of the CRL4CRBN E3 ubiquitin ligase, induces cancer cell death by targeting key neo-substrates for degradation. Despite this clinical significance, the physiological regulation of CRBN remains largely unknown. Herein we demonstrate that Wnt, the extracellular ligand of an essential signal transduction pathway, promotes the CRBN-dependent degradation of a subset of proteins. These substrates include Casein kinase 1α (CK1α), a negative regulator of Wnt signaling that functions as a key component of the β-Catenin destruction complex. Wnt stimulation induces the interaction of CRBN with CK1α and its resultant ubiquitination, and in contrast with previous reports does so in the absence of an IMiD. Mechanistically, the destruction complex is critical in maintaining CK1α stability in the absence of Wnt, and in recruiting CRBN to target CK1α for degradation in response to Wnt. CRBN is required for physiological Wnt signaling, as modulation of CRBN in zebrafish and Drosophila yields Wnt-driven phenotypes. These studies demonstrate an IMiD-independent, Wnt-driven mechanism of CRBN regulation and provide a means of controlling Wnt pathway activity by CRBN, with relevance for development and disease