Asymmetric inheritance of the apical domain and self-renewal of retinal ganglion cell progenitors depend on Anillin function.

Divisions that generate one neuronal lineage-committed and one self-renewing cell maintain the balance of proliferation and differentiation for the generation of neuronal diversity. The asymmetric inheritance of apical domains and components of the cell division machinery has been implicated in this process, and might involve interactions with cell fate determinants in regulatory feedback loops of an as yet unknown nature. Here, we report the dynamics of Anillin - an essential F-actin regulator and furrow component - and its contribution to progenitor cell divisions in the developing zebrafish retina. We find that asymmetrically dividing retinal ganglion cell progenitors position the Anillin-rich midbody at the apical domain of the differentiating daughter. anillin hypomorphic conditions disrupt asymmetric apical domain inheritance and affect daughter cell fate. Consequently, the retinal cell type composition is profoundly affected, such that the ganglion cell layer is dramatically expanded. This study provides the first in vivo evidence for the requirement of Anillin during asymmetric neurogenic divisions. It also provides insights into a reciprocal regulation between Anillin and the ganglion cell fate determinant Ath5, suggesting a mechanism whereby the balance of proliferation and differentiation is accomplished during progenitor cell divisions in vivo.journal articleresearch support, non-u.s. gov't2015 Mar 012015 02 05importe

Scientific opinion on the tolerable upper intake level for manganese

Following a request from the European Commission (EC), the EFSA Panel onNutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientificopinion on the tolerable upper intake level (UL) for manganese. Systematic reviewsof the literature of human and animal data were conducted to assess evidenceregarding excess manganese intake (including authorised manganese salts) andthe priority adverse health effect, i.e. manganese-induced neurotoxicity. Availablehuman and animal studies support neurotoxicity as a critical effect, however, dataare not sufficient and suitable to characterise a dose–response relationship andidentify a reference point for manganese-induced neurotoxicity. In the absenceof adequate data to establish an UL, estimated background dietary intakes (i.e.manganese intakes from natural dietary sources only) observed among high consumers (95th percentile) were used to provide an indication of the highest level of intake where there is reasonable confidence on the absence of adverse effects. A safe level of intake of 8 mg/day was established for adults ≥18years (including pregnant and lactating women) and ranged between 2 and 7 mg/day for other population groups. The application of the safe level of intake is more limited than an UL because the intake level at which the risk of adverse effects starts to increase is not defined

Scientific opinion on the tolerable upper intake level for manganese

Following a request from the European Commission (EC), the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for manganese. Systematic reviews of the literature of human and animal data were conducted to assess evidence regarding excess manganese intake (including authorised manganese salts) and the priority adverse health effect, i.e. manganese-induced neurotoxicity. Available human and animal studies support neurotoxicity as a critical effect, however, data are not sufficient and suitable to characterise a dose–response relationship and identify a reference point for manganese-induced neurotoxicity. In the absence of adequate data to establish an UL, estimated background dietary intakes (i.e. manganese intakes from natural dietary sources only) observed among high consumers (95th percentile) were used to provide an indication of the highest level of intake where there is reasonable confidence on the absence of adverse effects. A safe level of intake of 8 mg/day was established for adults ≥ 18 years (including pregnant and lactating women) and ranged between 2 and 7 mg/day for other population groups. The application of the safe level of intake is more limited than an UL because the intake level at which the risk of adverse effects starts to increase is not defined

Smart Tourism Destinations: Can the Destination Management Organizations Exploit Benefits of the ICTs? Evidences from a Multiple Case Study

Recent developments of ICTs enable new ways to experience tourism and conducted to the concept of smart tourism. The adoption of cutting-edge technologies and its combination with innovative organizational models fosters cooperation, knowledge sharing, and open innovation among service providers in tourism destination. Moreover, it offers innovative services to visitors. In few words, they become smart tourism destinations. In this paper, we report first results of the SMARTCAL project aimed at conceiving a digital platform assisting Destination Management Organizations (DMOs) in providing smart tourism services. A DMO is the organization charged with managing the tourism offer of a collaborative network, made up of service providers acting in a destination. In this paper, we adopted a multiple case studies approach to analyze five Italian DMOs. Our aims were to investigate (1) if, and how, successful DMOs were able to offer smart tourism services to visitors; (2) if the ICTs adoption level was related to the collaboration level among DMO partners. First results highlighted that use of smart technologies was still in an embryonic stage of development, and it did not depend from collaboration levels

Children Base Their Investment on Calculated Pay-Off

To investigate the rise of economic abilities during development we studied children aged between 3 and 10 in an exchange situation requiring them to calculate their investment based on different offers. One experimenter gave back a reward twice the amount given by the children, and a second always gave back the same quantity regardless of the amount received. To maximize pay-offs children had to invest a maximal amount with the first, and a minimal amount with the second. About one third of the 5-year-olds and most 7- and 10-year-olds were able to adjust their investment according to the partner, while all 3-year-olds failed. Such performances should be related to the rise of cognitive and social skills after 4 years

The Political Economy of Tax Reform in Bangladesh: Political Settlements, Informal Institutions and the Negotiation of Reform

political economy, tax reform, political settlementsThis paper explores the political economy of tax reform in Bangladesh over several decades, shedding light on the complex factors that account for unusually effective and sustained resistance to significant reform. We contend that it is necessary to understand both deep-seated formal and informal institutions and the micro-level incentives that shape the negotiation of short-term reform in order to comprehend tax outcomes. We describe a tax system that is highly informal, largely manual and characterised by high levels of discretion and corruption. However, despite appearing highly dysfunctional on the surface, this system serves the core interests of powerful political, economic and administrative actors. Underpinned by robust informal institutions, the current system delivers low and predictable tax rates to businesses, provides extensive discretion and opportunities for corruption to the tax administration, and acts as an important vehicle for political elites to raise funds and distribute patronage and economic rents. While the tax system has not been without reform, individual reform efforts have been constrained by the parameters of this broader settlement, leaving competing interest groups to pursue strategic gains at the margins while seeking to satisfy external reform demands. This tax bargain reflects Bangladesh’s broader political economy, which is characterised by entrenched informal institutions underpinning the combination of generally weak governance and high levels of economic growth – the so-called ‘paradox of Bangladesh’.DfID, NORA

Gastric inhibitory polypeptide receptor: association analyses for obesity of several polymorphisms in large study groups

<p>Abstract</p> <p>Background</p> <p>Gastric inhibitory polypeptide (GIP) is postulated to be involved in type 2 diabetes mellitus and obesity. It exerts its function through its receptor, GIPR. We genotyped three <it>GIPR </it>SNPs (rs8111428, rs2302382 and rs1800437) in German families with at least one obese index patient, two case-control studies and two cross-sectional population-based studies.</p> <p>Methods</p> <p>Genotyping was performed by MALDI-TOF, ARMS-PCR and RFLP. The family-study: 761 German families with at least one extremely obese child or adolescent (n = 1,041) and both parents (n = 1,522). Case-control study: (a) German obese children (n = 333) and (b) obese adults (n = 987) in comparison to 588 adult lean controls. The two cross-sectional population-based studies: KORA (n = 8,269) and SHIP (n = 4,310).</p> <p>Results</p> <p>We detected over-transmission of the A-allele of rs2302382 in the German families (p_TDT-Test= 0.0089). In the combined case-control sample, we estimated an odd ratio of 1.54 (95%CI 1.09;2.19, p_CA-Test= 0.014) for homozygotes of the rs2302382 A-allele compared to individuals with no A-allele. A similar trend was found in KORA where the rs2302382 A-allele led to an increase of 0.12 BMI units (p = 0.136). In SHIP, however, the A-allele of rs2302382 was estimated to contribute an average decrease of 0.27 BMI units (p-value = 0.031).</p> <p>Conclusion</p> <p>Our data suggest a potential relevance of <it>GIPR </it>variants for obesity. However, additional studies are warranted in light of the conflicting results obtained in one of the two population-based studies.</p