Ultrastructure of the Intramandibular Gland of Workers and Queens of the Stingless Bee, Melipona quadrifasciata

The intramandibular glands of workers and queens of Melipona quadrifasciata Lepeletier (Hymenoptera: Apidae), at different ages and from different functional groups, were studied using light and transmission electron microscopy. The results demonstrated that these glands are composed of two types of secretory structures: 1.A hypertrophied epidermis on the dorsal side of the mandible that is an epithelial gland. 2. Free secretory cells filling the inner spaces of the appendices that constitute a unicellular gland. The epithelial gland is larger in the young (1-2-day-old workers), and the gland becomes involuted during the nurse worker stage. The unicellular glands of the workers posses some secretion during all of the studied phases, but secretory activity is more intensive in the foraging workers. Vesicles of secretion are absent in the unicellular glands of queens. These results demonstrate that these glands show functional adaptations in different castes corresponding to the functions of each caste

The ethics of taxing sugar-sweetened beverages to improve public health

The World Health Organization highlights fiscal policies as priority interventions for the promotion of healthy eating in its Action Plan for the Prevention and Control of Non-communicable Diseases. The taxation of sugar sweetened beverages (SSBs) in particular is noted to be an effective measure, and SSBs taxes have already been implemented in several countries worldwide. However, although the evidence base suggests that this will be effective in helping to combat rising obesity rates, opponents of SSBs taxation argue that it is illiberal and paternalistic, and therefore should be avoided. Bioethical analysis may play an essential role in clarifying whether policymakers should adopt SSBs taxes as part of wider obesity strategy. In this article we argue that no single ethical theory can account for the complexities inherent in obesity prevention strategy, especially the liberal theories relied upon by opponents of SSBs taxation. We contend that a pluralist approach to the ethics of SSBs taxation must be adopted as the only suitable way of accounting for the multiple overlapping, and sometimes, conflicting factors that are relevant to determining the moral acceptability of such an intervention

IFNG +874T/A polymorphism is not associated with American tegumentary leishmaniasis susceptibility but can influence Leishmania induced IFN-γ production

<p>Abstract</p> <p>Background</p> <p>Interferon-gamma is a key cytokine in the protective responses against intracellular pathogens. A single nucleotide polymorphism (SNP) located in the first intron of the human IFN-γ gene can putatively influence the secretion of cytokine with an impact on infection outcome as demonstrated for tuberculosis and other complex diseases. Our aim was to investigate the putative association of IFNG+874T/A SNP with American tegumentary leishmaniasis (ATL) and also the influence of this SNP in the secretion of IFN-γ <it>in vitro</it>.</p> <p>Methods</p> <p>Brazilian ATL patients (78 cutaneous, CL, and 58 mucosal leishmaniasis, ML) and 609 healthy volunteers were evaluated. The genotype of +874 region in the IFN-γ gene was carried out by Amplification Refractory Mutational System (ARMS-PCR). <it>Leishmania</it>-induced IFN-γ production on peripheral blood mononuclear cell (PBMC) culture supernatants was assessed by ELISA.</p> <p>Results</p> <p>There are no differences between +874T/A SNP frequency in cases and controls or in ML versus CL patients. Cutaneous leishmaniasis cases exhibiting AA genotype produced lower levels of IFN-γ than TA/TT genotypes. In mucosal cases, high and low IFN-γ producers were clearly demonstrated but no differences in the cytokine production was observed among the IFNG +874T or A carriers.</p> <p>Conclusion</p> <p>Our results suggest that +874T/A polymorphism was not associated with either susceptibility or severity to leishmaniasis. Despite this, IFNG +874T/A SNP could be involved in the pathogenesis of leishmaniasis by influencing the amount of cytokine released by CL patients, although it could not prevent disease development. On the other hand, it is possible that in ML cases, other potential polymorphic regulatory genes such as TNF-α and IL-10 are also involved thus interfering with IFN-γ secretion.</p

‘Trendy’ cities: exploring the adoption of different types of social media by Portuguese municipalities

What are the determinants of social media adoption by local government? This ongoing research provides a tentative answer to this question by analysing the 308 municipalities in Portugal. Extending previous analyses of Facebook and/or Twitter usage levels, we examine why local governments adopt a particular social media platform. More concretely, we explore, with statistical analyses, the determinants of the adoption of different types of social media. We investigate the adoption of three extremely popular social media (i.e. Facebook, Twitter and YouTube) as well as possible alternatives to those, more popular, applications. Since these platforms have distinct natures and can serve diverse purposes, we examine to what extent aspects such as local government’s commitment to transparency and participation, administrative capacity, media landscape, and socio-demographic and economic factors can explain the adoption of certain social media platforms. The results show that, indeed, demographic characteristics and administrative capacity are important factors for the adoption of less popular social media. Surprisingly, we also observe a geographical difference in municipalities’ social media adoption, with the south, in this regard, being ‘trendier’, or more innovative, than the north.This paper is a result of the project “SmartEGOV: Harnessing EGOV for Smart Governance (Foundations, methods, Tools)/NORTE-01-0145-FEDER-000037”, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (EFDR). António Tavares acknowledges the financial support of the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Education and Science through national funds [Grant No. UID/CPO/0758/2019]

The transcriptional repressor protein NsrR senses nitric oxide directly via a [2Fe-2S] cluster

The regulatory protein NsrR, a member of the Rrf2 family of transcription repressors, is specifically dedicated to sensing nitric oxide (NO) in a variety of pathogenic and non-pathogenic bacteria. It has been proposed that NO directly modulates NsrR activity by interacting with a predicted [Fe-S] cluster in the NsrR protein, but no experimental evidence has been published to support this hypothesis. Here we report the purification of NsrR from the obligate aerobe Streptomyces coelicolor. We demonstrate using UV-visible, near UV CD and EPR spectroscopy that the protein contains an NO-sensitive [2Fe-2S] cluster when purified from E. coli. Upon exposure of NsrR to NO, the cluster is nitrosylated, which results in the loss of DNA binding activity as detected by bandshift assays. Removal of the [2Fe-2S] cluster to generate apo-NsrR also resulted in loss of DNA binding activity. This is the first demonstration that NsrR contains an NO-sensitive [2Fe-2S] cluster that is required for DNA binding activity

A systematic molecular and pharmacologic evaluation of AKT inhibitors reveals new insight into their biological activity.

Background AKT, a critical effector of the phosphoinositide 3-kinase (PI3K) signalling cascade, is an intensely pursued therapeutic target in oncology. Two distinct classes of AKT inhibitors have been in clinical development, ATP-competitive and allosteric. Class-specific differences in drug activity are likely the result of differential structural and conformational requirements governing efficient target binding, which ultimately determine isoform-specific potency, selectivity profiles and activity against clinically relevant AKT mutant variants.Methods We have carried out a systematic evaluation of clinical AKT inhibitors using in vitro pharmacology, molecular profiling and biochemical assays together with structural modelling to better understand the context of drug-specific and drug-class-specific cell-killing activity.Results Our data demonstrate clear differences between ATP-competitive and allosteric AKT inhibitors, including differential effects on non-catalytic activity as measured by a novel functional readout. Surprisingly, we found that some mutations can cause drug resistance in an isoform-selective manner despite high structural conservation across AKT isoforms. Finally, we have derived drug-class-specific phosphoproteomic signatures and used them to identify effective drug combinations.Conclusions These findings illustrate the utility of individual AKT inhibitors, both as drugs and as chemical probes, and the benefit of AKT inhibitor pharmacological diversity in providing a repertoire of context-specific therapeutic options

Thermal conductivity and thermal boundary resistance of nanostructures

International audienceWe present a fabrication process of low-cost superlattices and simulations related with the heat dissipation on them. The influence of the interfacial roughness on the thermal conductivity of semiconductor/semiconductor superlattices was studied by equilibrium and non-equilibrium molecular dynamics and on the Kapitza resistance of superlattice's interfaces by equilibrium molecular dynamics. The non-equilibrium method was the tool used for the prediction of the Kapitza resistance for a binary semiconductor/metal system. Physical explanations are provided for rationalizing the simulation results