Adaptation options for agricultural cultivation systems in the South Central Coast under the context of climate change: Assessment Report.

This report highlights the results of consultation meetings and field visits organized by the Department of Crop Production and the CGIAR Research Program on Climate Change, Agriculture and Food Security in Southeast Asia in association with the three offices of the Department of Agriculture and Rural Development in the South Central Coast provinces of Binh Thuan, Ninh Thuan, and Khanh Hoa, in combination with consultation with the provinces in the conference: “Summing up crops production in the Winter-Spring season in 2018-2019, implementing the Summer-Autumn season, Main rice season in 2019 for the South Central Coast and the Central Highlands” held by the Ministry of Agriculture and Rural Development in Tam Ky City, Quang Nam Province on 12 April 2019. The meetings underlined the progress made by the provinces on climate change adaptation and mitigation, options for risk reductions in agricultural production, and conversion of crop structure as results of implementing the guidelines of the provinces and the Sector, especially, solutions for reservation and efficient and economic use of water under the context of climate change. This assessment report also reviews some issues related to the agricultural transformation of the region in adapting to risks caused by climate change. They are based on comparative advantages in terms of geographical location and market of key agricultural products. This report also points out shortcomings in using land and unreasonable points in managing and using important natural resources, especially water, and provides recommendations for the agricultural transformation and inter-regional connection with the Central Highlands and the Southeast. The team also introduces climate-related risks maps and adaptation plans (CS MAP) which is applied in the five provinces in the Mekong Delta Region, and hopes this solution’s expansion shall be supported by the Ministry of Agriculture and Rural Development and the provinces

The hepatitis B virus pre-core protein p22 activates Wnt sgnaling

An emerging theme for Wnt-addicted cancers is that the pathway is regulated at multiple steps via various mechanisms. Infection with hepatitis B virus (HBV) is a major risk factor for liver cancer, as is deregulated Wnt signaling, however, the interaction between these two causes is poorly understood. To investigate this interaction, we screened the effect of the various HBV proteins for their effect on Wnt/β-catenin signaling and identified the pre-core protein p22 as a novel and potent activator of TCF/β-catenin transcription. The effect of p22 on TCF/β-catenin transcription was dose dependent and inhibited by dominant-negative TCF4. HBV p22 activated synthetic and native Wnt target gene promoter reporters, and TCF/β-catenin target gene expression in vivo. Importantly, HBV p22 activated Wnt signaling on its own and in addition to Wnt or β-catenin induced Wnt signaling. Furthermore, HBV p22 elevated TCF/β-catenin transcription above constitutive activation in colon cancer cells due to mutations in downstream genes of the Wnt pathway, namely APC and CTNNB1. Collectively, our data identifies a previously unappreciated role for the HBV pre-core protein p22 in elevating Wnt signaling. Understanding the molecular mechanisms of p22 activity will provide insight into how Wnt signaling is fine-tuned in cancer

Widespread FRA1-Dependent Control of Mesenchymal Transdifferentiation Programs in Colorectal Cancer Cells

Tumor invasion and metastasis involves complex remodeling of gene expression programs governing epithelial homeostasis. Mutational activation of the RAS-ERK is a frequent occurrence in many cancers and has been shown to drive overexpression of the AP-1 family transcription factor FRA1, a potent regulator of migration and invasion in a variety of tumor cell types. However, the nature of FRA1 transcriptional targets and the molecular pathways through which they promote tumor progression remain poorly understood. We found that FRA1 was strongly expressed in tumor cells at the invasive front of human colorectal cancers (CRCs), and that its depletion suppressed mesenchymal-like features in CRC cells in vitro. Genome-wide analysis of FRA1 chromatin occupancy and transcriptional regulation identified epithelial-mesenchymal transition (EMT)-related genes as a major class of direct FRA1 targets in CRC cells. Expression of the pro-mesenchymal subset of these genes predicted adverse outcomes in CRC patients, and involved FRA-1-dependent regulation and cooperation with TGFβ signaling pathway. Our findings reveal an unexpectedly widespread and direct role for FRA1 in control of epithelial-mesenchymal plasticity in CRC cells, and suggest that FRA1 plays an important role in mediating cross talk between oncogenic RAS-ERK and TGFβ signaling networks during tumor progression.This work was supported by project grants 1026228 and 1044168 (to A.S.D.) and Senior Research Fellowships (to R.D.H., R.B.P. and J.M.M.) from the National Health and Medical Research Council of Australia

Ubiquitin Ligase RNF146 Regulates Tankyrase and Axin to Promote Wnt Signaling

Canonical Wnt signaling is controlled intracellularly by the level of β-catenin protein, which is dependent on Axin scaffolding of a complex that phosphorylates β-catenin to target it for ubiquitylation and proteasomal degradation. This function of Axin is counteracted through relocalization of Axin protein to the Wnt receptor complex to allow for ligand-activated Wnt signaling. AXIN1 and AXIN2 protein levels are regulated by tankyrase-mediated poly(ADP-ribosyl)ation (PARsylation), which destabilizes Axin and promotes signaling. Mechanistically, how tankyrase limits Axin protein accumulation, and how tankyrase levels and activity are regulated for this function, are currently under investigation. By RNAi screening, we identified the RNF146 RING-type ubiquitin E3 ligase as a positive regulator of Wnt signaling that operates with tankyrase to maintain low steady-state levels of Axin proteins. RNF146 also destabilizes tankyrases TNKS1 and TNKS2 proteins and, in a reciprocal relationship, tankyrase activity reduces RNF146 protein levels. We show that RNF146, tankyrase, and Axin form a protein complex, and that RNF146 mediates ubiquitylation of all three proteins to target them for proteasomal degradation. RNF146 is a cytoplasmic protein that also prevents tankyrase protein aggregation at a centrosomal location. Tankyrase auto-PARsylation and PARsylation of Axin is known to lead to proteasome-mediated degradation of these proteins, and we demonstrate that, through ubiquitylation, RNF146 mediates this process to regulate Wnt signaling

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Stabilization of Urokinase and Urokinase Receptor mRNAs by HuR Is Linked to Its Cytoplasmic Accumulation Induced by Activated Mitogen-Activated Protein Kinase-Activated Protein Kinase 2

The mRNAs of urokinase plasminogen activator (uPA) and its receptor, uPAR, contain instability-determining AU-rich elements (AREs) in their 3′ untranslated regions. The cellular proteins binding to these RNA sequences (ARE(uPA/uPAR)) are not known. We show here that the mRNA-stabilizing factor HuR functionally interacts with these sequences. HuR stabilized an ARE(uPA)-containing RNA substrate in vitro and stabilized in HeLa Tet-off cells both endogenous uPA and uPAR mRNAs and a β-globin reporter mRNA containing the ARE(uPA). RNAi-mediated depletion of HuR in BT-549 and MDA-MB-231 cells significantly reduced the steady-state levels of endogenous uPA and uPAR mRNAs. Furthermore, we show that a constitutively active form of mitogen-activated protein kinase-activated protein kinase 2 (MK2), MK2-EE, has an ARE-mRNA-stabilizing effect that correlates with its ability to enhance the cytoplasmic accumulation of endogenous HuR, but not in cells cotransfected with a dominant negative version of MK2, MK2-K76R. These effects were mimicked by hydrogen peroxide treatment (oxidative stress), which resulted in the phosphorylation of endogenous MK2. In addition, hydrogen peroxide treatment enhanced the cytoplasmic binding of HuR to the ARE(uPA), which was abrogated in cells transfected with MK2-K76R. These results indicate a role for HuR and MK2 in regulating the expression of uPA and uPAR genes at the posttranscriptional level

The ‘Five Million Hectare Reforestation Program’ in Vietnam: An Analysis of its Implementation and Transaction Costs - A Case Study in Hoa Binh Province

This research study uses a qualitative approach to examine the implementation of the ‘Five Million Hectare Reforestation Program’ (the 5MHRP) in Vietnam, and to explore the underlying reasons for local people’s participation in the program. The study also uses a transactional model to examine the private transaction costs borne by farmers when carrying out forest management activities under the program. The study reveals that: (i) the implementation of the program was generally characterized by a top-down process, (ii) the principal contribution to household benefits derived from forest management activities was the collection and sale of non-timber forest products, not the subsidy provided by the government, (iii) the main challenges faced during implementation of the program were the low and fixed subsidies provided, the improper types of trees being planted, poor access to the forest, and a lack of awareness among local people towards the benefits to be derived from participation in the forest management program, and that (iv) under the program’s community contracts, attending meetings (52%) and self-monitoring activities (35%) constituted the largest proportion of total time spent on forest management, while under the individual contracts, self-monitoring activities (98%) were the main component. Participating in the planting and protection of forests under the program brought greater benefits to households than when involved in forest protection activities alone. The main implications of this study are that an increase of payments under both types of contract, and especially the community contract, as well as the provision of higher quality seedlings and fertilizers, need to be taken into consideration in future initiatives. In addition, local communities and authorities should be further empowered, and their contribution should be taken into consideration in future programs

Trabid, a new positive regulator of Wnt-induced transcription with preference for binding and cleaving K63-linked ubiquitin chains

A key effector of the canonical Wnt pathway is β-catenin, which binds to TCF/LEF factors to promote the transcription of Wnt target genes. In the absence of Wnt stimulation, β-catenin is phosphorylated constitutively, and modified with K48-linked ubiquitin for subsequent proteasomal degradation. Here, we identify Trabid as a new positive regulator of Wnt signaling in mammalian and Drosophila cells. Trabid show a remarkable preference for binding to K63-linked ubiquitin chains with its three tandem NZF fingers (Npl4 zinc finger), and it cleaves these chains with its OTU (ovarian tumor) domain. These activities of Trabid are required for efficient TCF-mediated transcription in cells with high Wnt pathway activity, including colorectal cancer cell lines. We further show that Trabid can bind to and deubiquitylate the APC tumor suppressor protein, a negative regulator of Wnt-mediated transcription. Epistasis experiments indicate that Trabid acts below the stabilization of β-catenin, and that it may affect the association or activity of the TCF–β-catenin transcription complex. Our results indicate a role of K63-linked ubiquitin chains during Wnt-induced transcription

Institutional arrangement and transaction cost in implementing of the National Five Million Hectares Reforestation Program in Vietnam [Abstract only].

In German Aerospace Center (DLR); Germany. Federal Ministry of Education and Research (BMBF). Mekong Environmental Symposium, Ho Chi Minh City, Vietnam, 5-7 March 2013. Abstract volume, Topic 03 - Mekong Basin forest dynamics and REDD+. Wessling, Germany: German Aerospace Center (DLR); Bonn, Germany: Federal Ministry of Education and Research (BMBF)