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The activity of vacuolar H+-ATPase (V-ATPase) in the apical membrane of blowfly (Calliphora vicina) salivary glands is regulated by the neurohormone serotonin (5-HT). 5-HT induces, via protein kinase A, the phosphorylation of V-ATPase subunit C and the assembly of V-ATPase holoenzymes. The protein phosphatase responsible for the dephosphorylation of subunit C and V-ATPase inactivation is not as yet known. We show here that inhibitors of protein phosphatases PP1 and PP2A (tautomycin, ocadaic acid) and PP2B (cyclosporin A, FK-506) do not prevent V-ATPase deactivation and dephosphorylation of subunit C. A decrease in the intracellular Mg2+ level caused by loading secretory cells with EDTA-AM leads to the activation of proton pumping in the absence of 5-HT, prolongs the 5-HT-induced response in proton pumping, and inhibits the dephosphorylation of subunit C. Thus, the deactivation of V-ATPase is most probably mediated by a protein phosphatase that is insensitive to okadaic acid and that requires Mg2+, namely, a member of the PP2C protein family. By molecular biological techniques, we demonstrate the expression of at least two PP2C protein family members in blowfly salivary glands. © 2009 Wiley Periodicals, Inc.
Equity crowdfunding
(2021)
In this study, we explore the development of equity crowdfunding (ECF) over the next 5 to 10 years by conducting an international Delphi study. Our results indicate that the ECF market is expected to grow significantly. However, it is unlikely to disrupt other forms of financing and will not cover all SME financing needs. ECF will remain a funding technique for SMEs and small investors; it is unlikely to attract large corporations or institutional investors. Platforms will impose stricter requirements for capital raisers, expand their services, and innovate their business models. National governments will probably partly liberalize the ECF market.
The availability of high-throughput data from transcriptomics and metabolomics technologies provides the opportunity to characterize the transcriptional effects on metabolism. Here we propose and evaluate two computational approaches rooted in data reduction techniques to identify and categorize transcriptional effects on metabolism by combining data on gene expression and metabolite levels. The approaches determine the partial correlation between two metabolite data profiles upon control of given principal components extracted from transcriptomics data profiles. Therefore, they allow us to investigate both data types with all features simultaneously without doing preselection of genes. The proposed approaches allow us to categorize the relation between pairs of metabolites as being under transcriptional or post-transcriptional regulation. The resulting classification is compared to existing literature and accumulated evidence about regulatory mechanism of reactions and pathways in the cases of Escherichia coil, Saccharomycies cerevisiae, and Arabidopsis thaliana.
It is the intention of this study to contribute to further rethinking and innovating in the Microcredit business which stands at a turning point – after around 40 years of practice it is endangered to fail as a tool for economic development and to become a doubtful finance product with a random scope instead. So far, a positive impact of Microfinance on the improvement of the lives of the poor could not be confirmed. Over-indebtment of borrowers due to the pre-dominance of consumption Microcredits has become a widespread problem. Furthermore, a rising number of abusive and commercially excessive practices have been reported.
In fact, the Microfinance sector appears to suffer from a major underlying deficit: there does not exist a coherent and transparent understanding of its meaning and objectives so that Microfinance providers worldwide follow their own approaches of Microfinance which tend to differ considerably from each other.
In this sense the study aims at consolidating the multi-faced and very often confusingly different Microcredit profiles that exist nowadays. Subsequently, in this study, the Microfinance spectrum will be narrowed to one clear-cut objective, in fact away from the mere monetary business transactions to poor people it has gradually been reduced to back towards a tool for economic development as originally envisaged by its pioneers.
Hence, the fundamental research question of this study is whether, and under which conditions, Microfinance may attain a positive economic impact leading to an improvement of the living of the poor.
The study is structured in five parts: the three main parts (II.-IV.) are surrounded by an introduction (I.) and conclusion (V.). In part II., the Microfinance sector is analysed critically aiming to identify the challenges persisting as well as their root causes. In the third part, a change to the macroeconomic perspective is undertaken in oder to learn about the potential and requirements of small-scale finance to enhance economic development, particularly within the economic context of less developed countries. By consolidating the insights gained in part IV., the elements of a new concept of Microfinance with the objecitve to achieve economic development of its borrowers are elaborated.
Microfinance is a rather sensitive business the great fundamental idea of which is easily corruptible and, additionally, the recipients of which are predestined victims of abuse due to their limited knowledge in finance. It therefore needs to be practiced responsibly, but also according to clear cut definitions of its meaning and objectives all institutions active in the sector should be devoted to comply with. This is especially relevant as the demand for Microfinance services is expected to rise further within the years coming. For example, the recent refugee migration movement towards Europe entails a vast potential for Microfinance to enable these people to make a new start into economic life. This goes to show that Microfinance may no longer mainly be associated with a less developed economic context, but that it will gain importance as a financial instrument in the developed economies, too.
In order to function properly, organisms have a complex control mechanism, in which a given gene is expressed at a particular time and place. One way to achieve this control is to regulate the initiation of transcription. This step requires the assembly of several components, i.e., a basal/general machinery common to all expressed genes, and a specific/regulatory machinery, which differs among genes and is the responsible for proper gene expression in response to environmental or developmental signals. This specific machinery is composed of transcription factors (TFs), which can be grouped into evolutionarily related gene families that possess characteristic protein domains. In this work we have exploited the presence of protein domains to create rules that serve for the identification and classification of TFs. We have modelled such rules as a bipartite graph, where families and protein domains are represented as nodes. Connections between nodes represent that a protein domain should (required rule) or should not (forbidden rule) be present in a protein to be assigned into a TF family. Following this approach we have identified putative complete sets of TFs in plant species, whose genome is completely sequenced: Cyanidioschyzon merolae (red algae), Chlamydomonas reinhardtii (green alga), Ostreococcus tauri (green alga), Physcomitrella patens (moss), Arabidopsis thaliana (thale cress), Populus trichocarpa (black cottonwood) and Oryza sativa (rice). The identification of the complete sets of TFs in the above-mentioned species, as well as additional information and reference literature are available at http://plntfdb.bio.uni-potsdam.de/. The availability of such sets allowed us performing detailed evolutionary studies at different levels, from a single family to all TF families in different organisms in a comparative genomics context. Notably, we uncovered preferential expansions in different lineages, paving the way to discover the specific biological roles of these proteins under different conditions. For the basic leucine zipper (bZIP) family of TFs we were able to infer that in the most recent common ancestor (MRCA) of all green plants there were at least four bZIP genes functionally involved in oxidative stress and unfolded protein responses that are bZIP-mediated processes in all eukaryotes, but also in light-dependent regulations. The four founder genes amplified and diverged significantly, generating traits that benefited the colonization of new environments. Currently, following the approach described above, up to 57 TF and 11 TR families can be identified, which are among the most numerous transcription regulatory families in plants. Three families of putative TFs predate the split between rhodophyta (red algae) and chlorophyta (green algae), i.e., G2-like, PLATZ, and RWPRK, and may have been of particular importance for the evolution of eukaryotic photosynthetic organisms. Nine additional families, i.e., ABI3/VP1, AP2-EREBP, ARR-B, C2C2-CO-like, C2C2-Dof, PBF-2-like/Whirly, Pseudo ARR-B, SBP, and WRKY, predate the split between green algae and streptophytes. The identification of putative complete list of TFs has also allowed the delineation of lineage-specific regulatory families. The families SBP, bHLH, SNF2, MADS, WRKY, HMG, AP2-EREBP and FHA significantly differ in size between algae and land plants. The SBP family of TFs is significantly larger in C. reinhardtii, compared to land plants, and appears to have been lost in the prasinophyte O. tauri. The families bHLH, SNF2, MADS, WRKY, HMG, AP2-EREBP and FHA preferentially expanded with the colonisation of land, and might have played an important role in this great moment in evolution. Later, after the split of bryophytes and tracheophytes, the families MADS, AP2-EREBP, NAC, AUX/IAA, PHD and HRT have significantly larger numbers in the lineage leading to seed plants. We identified 23 families that are restricted to land plants and that might have played an important role in the colonization of this new habitat. Based on the list of TFs in different species we have started to develop high-throughput experimental platforms (in rice and C. reinhardtii) to monitor gene expression changes of TF genes under different genetic, developmental or environmental conditions. In this work we present the monitoring of Arabidopsis thaliana TFs during the onset of senescence, a process that leads to cell and tissue disintegration in order to redistribute nutrients (e.g. nitrogen) from leaves to reproductive organs. We show that the expression of 185 TF genes changes when leaves develop from half to fully expanded leaves and finally enter partial senescence. 76% of these TFs are down-regulated during senescence, the remaining are up-regulated. The identification of TFs in plants in a comparative genomics setup has proven fruitful for the understanding of evolutionary processes and contributes to the elucidation of complex developmental programs.
Plasticity of human growth
(2020)
Background:
This systematic review aimed at collecting, analyzing and summarizing scientific studies focusing on psychosocial factors that influence linear growth among humans.
Methods:
The online database "PubMed" was used in order to acquire suitable scientific studies. These studies were evaluated based on clearly defined criteria that determine whether a study was to be excluded or included in the literature review. In the end, a total sum of 36 studies remained, which were carefully analyzed and used to generate an overview of the association between psychosocial factors and linear growth.
Results:
In the 36 reviewed studies, different social and psychological factors, such as socioeconomic status, parental education or emotional deprivation were set in relation to physical growth among humans. The studies were listed and summarized, depending on the investigated psychosocial factor. A clear association between psychosocial factors and growth could be observed in most of the reviewed studies. Discussion: Based on the results of the reviewed studies it could be concluded that the regulation of linear growth is also subject to different psychosocial factors. The way in which the developing human and the specific social environment interact seemed to have a major impact on linear growth. Statusspecific stress was discussed as one possible explanation for the regulating mechanism of human linear growth.
Nitrogen lipid regulator (NlpR) is a pleiotropic regulator that positively controls genes associated with both nitrogen and lipid metabolism in the oleaginous bacterium Rhodococcus jostii RHA1. In this study, we investigated the effect of nlpR disruption and overexpression on the assimilation of C-13-labeled glucose as carbon source, during cultivation of cells under nitrogen-limiting and nitrogen-rich conditions, respectively. Label incorporation into the total lipid extract (TLE) fraction was about 30% lower in the mutant strain in comparison with the wild type strain under low-nitrogen conditions. Moreover, a higher C-13 abundance (similar to 60%) into the extracellular polymeric substance fraction was observed in the mutant strain, nlpR disruption also promoted a decrease in the label incorporation into several TLE-derivative fractions including neutral lipids (NL), glycolipids (GL), phospholipids (PL), triacylglycerols (TAG), diacylglycerols (DAG), and free fatty acids (FFA), with the DAG being the most affected. In contrast, the nlpR overexpression in RHA1 cells under nitrogen-rich conditions produced an increase of the label incorporation into the TLE and its derivative NL and PL fractions, the last one being the highest C-13 enriched. In addition, a higher C-13 enrichment occurred in the TAG, DAG, and FFA fractions after nlpR induction, with the FFA fraction being the most affected within the TLE. Isotopic-labeling experiments demonstrated that NlpR regulator is contributing in oleaginous phenotype of R. jostii RHA1 to the allocation of carbon into the different lipid fractions in response to nitrogen levels, increasing the rate of carbon flux into lipid metabolism.
In silico identification of genes regulated by abscisic acid in Arabidopsis thaliana (L.) Heynh.
(2005)
Abscisic acid (ABA) is a major plant hormone that plays an important role during plant growth and development. During vegetative growth ABA mediates (in part) responses to various environmental stresses such as cold, drought and high salinity. The response triggered by ABA includes changes in the transcript level of genes involved in stress tolerance. The aim of this project was the In silico identification of genes putatively regulated by ABA in A. thaliana. In silico predictions were combined with experimental data in order to evaluate the reliability of computational predictions. Taking advantage of the genome sequence of A. thaliana publicly available since 2000, 1 kb upstream sequences were screened for combinations of cis-elements known to be involved in the regulation of ABA-responsive genes. It was found that around 10 to 20 percent of the genes of A. thaliana might be regulated by ABA. Further analyses of the predictions revealed that certain combinations of cis-elements that confer ABA-responsiveness were significantly over-represented compared with results in random sequences and with random expectations. In addition, it was observed that other combinations that confer ABA-responsiveness in monocotyledonous species might not be functional in A. thaliana. It is proposed that ABA-responsive genes in A. thaliana show pairs of ABRE (abscisic acid responsive element) with MYB binding sites, DRE (dehydration responsive element) or with itself. The analysis of the distances between pairs of cis-elements suggested that pairs of ABREs are bound by homodimers of ABRE binding proteins. In contrast, pairs between MYB binding sites and ABRE, or DRE and ABRE showed a distance between cis-elements that suggested that the binding proteins interact through protein complexes and not directly. The comparison of computational predictions with experimental data confirmed that the regulatory mechanisms leading to the induction or repression of genes by ABA is very incompletely understood. It became evident that besides the cis-elements proposed in this study to be present in ABA-responsive genes, other known and unknown cis-elements might play an important role in the transcriptional regulation of ABA-responsive genes. For example, auxin-related cis elements, or the cis-elements recognized by the NAM-family of transcription factors (Non-Apical meristem). This work documents the use of computational and experimental approaches to analyse possible interactions between cis-elements involved in the regulation of ABA-responsive genes. The computational predictions allowed the distinction between putatively relevant combinations of cis-elements from irrelevant combinations of cis-elements in ABA-responsive genes. The comparison with experimental data allowed to identify certain cis-elements that have not been previously associated to the ABA-mediated transcriptional regulation, but that might be present in ABA-responsive genes (e.g. auxin responsive elements). Moreover, the efforts to unravel the gene regulatory network associated with the ABA-signalling pathway revealed that NAM-transcription factors and their corresponding binding sequences are important components of this network.
The educational sector currently faces a massive digital transformation with various digital offerings entering the market. To provide some orientation in this transforming space, a national digital education platform (NDEP) is under development in Germany as part of a nationwide flagship project. On the one hand, in efficiently connecting the relevant stakeholders to each other and to value-adding education-related offerings, various benefits emerge. On the other hand, monopolising the educational sector and influencing the respective market through a state-controlled platform bears potential regulatory risks from misuse of power by the platform to malpractice by the users. Against this background, we aim to identify and systematise these potential drawbacks prior to the platform’s actual development and implementation. We pursue a qualitative, interpretivist approach for policy analysis, based on ten elite interviews and two workshops. Our results are threefold: (1) We capture the consolidated NDEP architecture; (2) We categorise the range of relevant functions and value propositions of the NDEP; (3) We derive 23 regulatory areas of conflict across the three building blocks that result from the potential ecosystem and function scope configurations of the NDEP. As a contribution to research, we shed new interdisciplinary light on the governance and infrastructure of public-private platforms that enable innovation and collaboration while integrating respective market segments. As a contribution to practice, we provide clear guidance for policy-makers in strategizing the development and governance of and through national digital platforms in education.
On 21 April 2021, the European Commission presented its long-awaited proposal for a Regulation “laying down harmonized rules on Artificial Intelligence”, the so-called “Artificial Intelligence Act” (AIA). This article takes a critical look at the proposed regulation. After an introduction (1), the paper analyzes the unclear preemptive effect of the AIA and EU competences (2), the scope of application (3), the prohibited uses of Artificial Intelligence (AI) (4), the provisions on high-risk AI systems (5), the obligations of providers and users (6), the requirements for AI systems with limited risks (7), the enforcement system (8), the relationship of the AIA with the existing legal framework (9), and the regulatory gaps (10). The last section draws some final conclusions (11).
On 21 April 2021, the European Commission presented its long-awaited proposal for a Regulation “laying down harmonized rules on Artificial Intelligence”, the so-called “Artificial Intelligence Act” (AIA). This article takes a critical look at the proposed regulation. After an introduction (1), the paper analyzes the unclear preemptive effect of the AIA and EU competences (2), the scope of application (3), the prohibited uses of Artificial Intelligence (AI) (4), the provisions on high-risk AI systems (5), the obligations of providers and users (6), the requirements for AI systems with limited risks (7), the enforcement system (8), the relationship of the AIA with the existing legal framework (9), and the regulatory gaps (10). The last section draws some final conclusions (11).
The limitations and possibilities of the state in solving societal problems are perennial issues in the political and policy sciences and increasingly so in studies of environmental politics. With the aim of better understanding the role of the state in addressing environmental degradation through policy making, this article investigates the nexus between the environmental policy outputs and the environmental performance. Drawing on three theoretical perspectives on the state and market nexus in the environmental dilemma, we identify five distinct pathways. We then examine the extent to which these pathways are manifested in the real world. Our empirical investigation covers up to 37 countries for the period 1970–2010. While we see no global pattern of linkages between policy outputs and performance, our exploratory analysis finds evidence of policy effects, which suggest that the state can, under certain circumstances, improve the environment through policy making.
In this study, we investigated the cognitive-emotional interplay by measuring the effects of executive competition (Pessoa, 2013), i.e., how inhibitory control is influenced when emotional information is encountered. Sixty-three children (8 to 9 years of age) participated in an inhibition task (central task) accompanied by happy, sad, or neutral emoticons (displayed in the periphery). Typical interference effects were found in the main task for speed and accuracy, but in general, these effects were not additionally modulated by the peripheral emoticons indicating that processing of the main task exhausted the limited capacity such that interference from the task-irrelevant, peripheral information did not show (Pessoa, 2013). Further analyses revealed that the magnitude of interference effects depended on the order of congruency conditions: when incongruent conditions preceded congruent ones, there was greater interference. This effect was smaller in sad conditions, and particularly so at the beginning of the experiment. These findings suggest that the bottom-up perception of task-irrelevant emotional information influenced the top-down process of inhibitory control among children in the sad condition when processing demands were particularly high. We discuss if the salience and valence of the emotional stimuli as well as task demands are the decisive characteristics that modulate the strength of this relation.
The regulation of protein function by modulating the surface charge status via sequence-locally enriched phosphorylation sites (P-sites) in so called phosphorylation "hotspots" has gained increased attention in recent years. We set out to identify P-hotspots in the model plant Arabidopsis thaliana. We analyzed the spacing of experimentally detected P-sites within peptide-covered regions along Arabidopsis protein sequences as available from the PhosPhAt database. Confirming earlier reports (Schweiger and Lanial, 2010), we found that, indeed, P-sites tend to cluster and that distributions between serine and threonine P-sites to their respected closest next P-site differ significantly from those for tyrosine P-sites. The ability to predict P-hotspots by applying available computational P-site prediction programs that focus on identifying single P-sites was observed to be severely compromised by the inevitable interference of nearby P-sites. We devised a new approach, named HotSPotter, for the prediction of phosphorylation hotspots. HotSPotter is based primarily on local amino acid compositional preferences rather than sequence position-specific motifs and uses support vector machines as the underlying classification engine. HotSPotter correctly identified experimentally determined phosphorylation hotspots in A. thaliana with high accuracy. Applied to the Arabidopsis proteome, HotSPotter-predicted 13,677 candidate P-hotspots in 9,599 proteins corresponding to 7,847 unique genes. Hotspot containing proteins are involved predominantly in signaling processes confirming the surmised modulating role of hotspots in signaling and interaction events. Our study provides new bioinformatics means to identify phosphorylation hotspots and lays the basis for further investigating novel candidate P-hotspots. All phosphorylation hotspot annotations and predictions have been made available as part of the PhosPhAt database at http://phosphat.mpimp-golm.mpg.de.
In the area of cardiac monitoring, the use of digitally driven technologies is on the rise. While the development of medical products is advancing rapidly, allowing for new use-cases in cardiac monitoring and other areas, regulatory and legal requirements that govern market access are often evolving slowly, sometimes creating market barriers. This article gives a brief overview of the existing clinical studies regarding the use of smart wearables in cardiac monitoring and provides insight into the main regulatory and legal aspects that need to be considered when such products are intended to be used in a health care setting. Based on this brief overview, the article elaborates on the specific requirements in the main areas of authorization/certification and reimbursement/compensation, as well as data protection and data security. Three case studies are presented as examples of specific market access procedures: the USA, Germany, and Belgium. This article concludes that, despite the differences in specific requirements, market access pathways in most countries are characterized by a number of similarities, which should be considered early on in product development. The article also elaborates on how regulatory and legal requirements are currently being adapted for digitally driven wearables and proposes an ongoing evolution of these requirements to facilitate market access for beneficial medical technology in the future.
High-growth firms (HGFs) are important for job creation and productivity growth. We investigate the relationship between product and labour market regulations, as well as the quality of regional governments that implement these regulations, and the development of HGFs across European regions. Using data from Eurostat, the Organisation for Economic Co-operation and Development (OECD), World Economic Forum (WEF), and Gothenburg University, we show that both regulatory stringency and the quality of the regional government relate to the regional shares of HGFs. In particular, we find that the effect of labour and product market regulations is moderated by the quality of regional government. Depending on the quality of regional governments, regulations may have a ‘good, bad or ugly’ influence on the development of HGFs. Our findings contribute to the debate on the effects of regulations and offer important building blocks to develop tailored policy measures that may influence the development of HGFs in a region.