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Relatedness has often been shown to have a central role in regional diversification. Knowledge flows between related industries are an important source of innovation, leading to industry growth and the establishment of new industries. Earlier studies have focused on dynamic diversification into new industries, but in this study, we emphasize static diversification, that is, changes in the balance between existing industries in a region. We use linked employer–employee data from Denmark and construct a range of measures at the level of regional industries. The role of relatedness in static diversification 2008–2013 is then analyzed based on industry characteristics in 2008. We find that relatedness plays a more important role in regions that are either spatially peripheral or economically non-peripheral, while relatedness has no relationship to static diversification on average. In addition to the empirical result, we contribute by comparing indices of relatedness, suggesting an alternative employment-weighted index, and conceptualizing relatedness as itself a disparity dimension of diversity. We finally ask how static and dynamic diversification affect disparity. We find that human capital intensity plays an important role in the link between diversification and the evolution of disparity. [ABSTRACT FROM AUTHOR]

We present a data structure that, given a graph G of n vertices and m edges, and a suitable pair of nested r-divisions of G, preprocesses G in O (m + n) time and handles any series of edge-deletions in O(m) total time while answering queries to pairwise biconnectivity in worst-case O(1) time. In case the vertices are not biconnected, the data structure can return a cutvertex separating them in worst-case O(1) time. As an immediate consequence, this gives optimal amortized decremental biconnectivity, 2-edge connectivity, and connectivity for large classes of graphs, including planar graphs and other minor free graphs. [ABSTRACT FROM AUTHOR]

Background: Scavenging indigenous village chickens play a vital role in sub-Saharan Africa, sustaining the livelihood of millions of farmers. These chickens are exposed to vastly different environments and feeds compared to commercial chickens. In this study, we analysed the caecal microbiota of 243 Ethiopian village chickens living in different altitude-dependent agro-ecologies. Results: Differences in bacterial diversity were significantly correlated with differences in specific climate factors, topsoil characteristics, and supplemental diets provided by farmers. Microbiota clustered into three enterotypes, with one particularly enriched at high altitudes. We assembled 9977 taxonomically and functionally diverse metagenome-assembled genomes. The vast majority of these were not found in a dataset of previously published chicken microbes or in the Genome Taxonomy Database. Conclusions: The wide functional and taxonomic diversity of these microbes highlights their importance in the local adaptation of indigenous poultry, and the significant impacts of environmental factors on the microbiota argue for further discoveries in other agro-ecologies. EEwR8PKafK2-LVnkA2-YG- Video Abstract [ABSTRACT FROM AUTHOR]

In this paper, we discuss the impact of artificial intelligence (AI) on innovation dynamics and argue that AI has affected innovation dynamics in at least two distinct ways. First, innovation using AI has unique dynamics that are characterised by data playing a central role and the increasing importance of external collaboration; however, data security and privacy issues also present new risks to external collaboration. When innovating in AI, collaboration with customers and competitors is critical, yet there are considerable risks associated with data sharing. Second, unique organisational challenges emerge during the diffusion of AI innovations, because adopting AI in an organisation not only results in the need for additional employee competencies but also challenges organisational power structures. We also discuss the merits of AI as a general purpose technology and argue that conclusions about AI in relation to innovation dynamics are likely to change when generative AI is widely adopted. [ABSTRACT FROM AUTHOR]

OSA is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent upper airway obstruction and hypoxia, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition, and subsequent transplantation of fecal matter to other animals induced changes in BP and glucose metabolism. Does OSA in adults associate with the composition and functional potential of the human gut microbiota? We used respiratory polygraphy data from up to 3,570 individuals 50 to 64 years of age from the population-based Swedish Cardiopulmonary bioimage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia, and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, onsite anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register. We found that all three OSA parameters were associated with lower diversity of species in the gut. Furthermore, in multivariable-adjusted analysis, the OSA-related hypoxia parameters were associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsella aerofaciens. The latter species was also independently associated with increased systolic BP. Furthermore, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Finally, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively. OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA. [ABSTRACT FROM AUTHOR]

In the online bipartite matching problem with replacements, all the vertices on one side of the bipartition are given, and the vertices on the other side arrive one-by-one with all their incident edges. The goal is to maintain a maximum matching while minimizing the number of changes (replacements) to the matching. We show that the greedy algorithm that always takes the shortest augmenting path from the newly inserted vertex (denoted the SAP protocol) uses at most amortized O(log2 n) replacements per insertion, where n is the total number of vertices inserted. This is the first analysis to achieve a polylogarithmic number of replacements for any replacement strategy, almost matching the Ω(logn) lower bound. The previous best strategy known achieved amortized O(√n) replacements [Bosek, Leniowski, Sankowski, Zych, FOCS 2014]. For the SAP protocol in particular, nothing better than the trivial O(n) bound was known except in special cases. Our analysis immediately implies the same upper bound of O(log2 n) reassignments for the capacitated assignment problem, where each vertex on the static side of the bipartition is initialized with the capacity to serve a number of vertices. We also analyze the problem of minimizing the maximum server load. We show that if the final graph has maximum server load L, then the SAP protocol makes amortized O(min{L log2 n,√n log n}) reassignments. We also show that this is close to tight, because Ω(min{L, √n}) reassignments can be necessary. [ABSTRACT FROM AUTHOR]

Here, we present a longitudinal shotgun sequencing metagenomics study of 16 healthy, Danish women in the reproductive age. The aim of the study was to investigate whether lactobacilli, orally consumed, had any impact on the vaginal microbiome and its functional potential. The 16 women aged 19–45 years were recruited from Copenhagen, Denmark. One baseline vaginal sample (Day 0) and two study samples (Days 25–30 and Days 55–60, respectively), were sampled. The vaginal samples were analyzed by shotgun metagenomics. We detected 26 species in the vaginal microbiota of the 16 women, of which six belonged to the Lactobacillus genus. We observed three vaginal microbiome clusters mainly dominated by Gardnerella vaginalis, Lactobacillus iners, or Lactobacillus crispatus. The oral probiotic had no detectable effect on either the composition or the functional potential of the vaginal microbiota. Most of the study subjects (11 out of 16 women) exhibited only minor changes in the vaginal microbiome during the treatment with probiotics. Any compositional changes could not be associated to the probiotic treatment. Future studies may benefit from an increased number of participants, and administration of the probiotics during conditions with bacterial imbalance (e.g., during/after antibiotic treatment) or the use of different Lactobacillus spp. known to colonize the vagina. [ABSTRACT FROM AUTHOR]

Human gut microbiota produce a variety of molecules, some of which enter the bloodstream and impact health. Conversely, dietary or pharmacological compounds may affect the microbiota before entering the circulation. Characterization of these interactions is an important step towards understanding the effects of the gut microbiota on health. In this cross-sectional study, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for a detailed characterization of the gut microbiota and plasma metabolome, respectively, of 8583 participants invited at age 50 to 64 from the population-based Swedish CArdioPulmonary bioImage Study. Here, we find that the gut microbiota explain up to 58% of the variance of individual plasma metabolites and we present 997 associations between alpha diversity and plasma metabolites and 546,819 associations between specific gut metagenomic species and plasma metabolites in an online atlas (https://gutsyatlas.serve.scilifelab.se/). We exemplify the potential of this resource by presenting novel associations between dietary factors and oral medication with the gut microbiome, and microbial species strongly associated with the uremic toxin p-cresol sulfate. This resource can be used as the basis for targeted studies of perturbation of specific metabolites and for identification of candidate plasma biomarkers of gut microbiota composition. Here, Dekkers et al. characterize associations of 1528 gut metagenomic species with the plasma metabolome in 8583 participants of the SCAPIS Study, and find that gut microbiota explain up to 58% of the variance of individual plasma metabolites. [ABSTRACT FROM AUTHOR]

This study explores the relationship between mobility patterns, occupational choices and performance outcomes of university graduates from metropolitan and peripheral areas. After statistical matching, we find opposite outcomes for geographically mobile wage earners and entrepreneurs. Graduates from the periphery who stay in the study region to work have an inferior performance outcome compared with those who move to the metropolitan region. This 'penalty' is not present for non-movers in metropolitan areas. Non-mobile entrepreneurs benefit from attachment to their home region, in particular in the periphery. These findings can help direct regional policy aimed at retaining graduates and promoting regional development. [ABSTRACT FROM AUTHOR]

Based on a unique dataset on the use of artificial intelligence (AI) among employees in Denmark, we investigate within‐job relationships between AI use and skill requirements. We show that the effects of AI are varied and depend on whether AI is used for providing orders to humans or providing information for further human handling and in which occupation it is used. AI may enhance or augment skills through, for example, the increased use of high‐performance work practices, or it may increase work pace constraints and reduce employee autonomy. The results imply that the diffusion of AI can increase inequalities in the labour market by augmenting skills used in high‐skill jobs, although having relatively more adverse impacts on other jobs. We use additive noise modelling to establish the likely direction of causality in our results and find that the direction of causality is from AI use to skill requirements. [ABSTRACT FROM AUTHOR]

This article explores changes in the organization of work in European nations over 2000-2010. Results show a decline in the Discretionary Learning (DL). Periods of economic expansion tend to be DL enhancing, while periods of economic stagnation tend to reinforce the use of more hierarchical forms of work organization. More generally, the results show that cross-country comparisons do not provide a sound basis for drawing conclusions about how the evolution of national labor market policies impact on changes in work organization overtime within nations. [ABSTRACT FROM AUTHOR]

Background: Microbial dysbiosis with increased Staphylococcus aureus (S. aureus) colonization on the skin is a hallmark of atopic dermatitis (AD), however most microbiome studies focus on bacteria in the flexures and the microbial composition at other body sites have not been studied systematically. Objectives: The aim of the study is to characterize the skin microbiome, including bacteria, fungi and virus, at different body sites in relation to AD, lesional state, and S. aureus colonization, and to test whether the nares could be a reservoir for S. aureus strain colonization. Methods: Using shotgun metagenomics we characterized microbial compositions from 14 well defined skin sites from 10 patients with AD and 5 healthy controls. Results: We found clear differences in microbial composition between AD and controls at multiple skin sites, most pronounced on the flexures and neck. The flexures exhibited lower alpha-diversity and were colonized by S. aureus, accompanied by S. epidermidis in lesions. Malassezia species were absent on the neck in AD. Virus mostly constituted Propionibacterium and Staphylococcusphages, with increased abundance of Propionibacterium phages PHL041 and PHL092 and Staphylococcus epidermidis phages CNPH82 and PH15 in AD. In lesional samples, both the genus Staphylococcus and Staphylococcus phages were more abundant. S. aureus abundance was higher across all skin sites except from the feet. In samples where S. aureus was highly abundant, lower abundances of S. hominis and Cutibacterium acnes were observed. M. osloensis and M. luteus were more abundant in AD. By single nucleotide variant analysis of S. aureus we found strains to be subject specific. On skin sites some S. aureus strains were similar and some dissimilar to the ones in the nares. Conclusions: Our data indicate a global and site-specific dysbiosis in AD, involving both bacteria, fungus and virus. When defining targeted treatment clinicians should both consider the individual and skin site and future research into potential crosstalk between microbiota in AD yields high potential. [ABSTRACT FROM AUTHOR]

Interactions between host and gut microbial communities are modulated by diets and play pivotal roles in immunological homeostasis and health. We show that exchanging the protein source in a high fat, high sugar, westernized diet from casein to whole-cell lysates of the non-commensal bacterium Methylococcus capsulatus Bath is sufficient to reverse western diet-induced changes in the gut microbiota to a state resembling that of lean, low fat diet-fed mice, both under mild thermal stress (T22 °C) and at thermoneutrality (T30 °C). Concomitant with microbiota changes, mice fed the Methylococcus-based western diet exhibit improved glucose regulation, reduced body and liver fat, and diminished hepatic immune infiltration. Intake of the Methylococcu-based diet markedly boosts Parabacteroides abundances in a manner depending on adaptive immunity, and upregulates triple positive (Foxp3+RORγt+IL-17+) regulatory T cells in the small and large intestine. Collectively, these data point to the potential for leveraging the use of McB lysates to improve immunometabolic homeostasis. Dietary changes can impact the microbial constitution of the gastrointestinal tract and modulate the local immune response. Here, the authors show supplementation using lysates of Methylococcus capsulatus Bath result in changes to the microbiota, modulate Treg populations and metabolic read outs in a dietary control murine model. [ABSTRACT FROM AUTHOR]

Private sector R&D is largely concentrated in a few multinational companies (MNCs). The mobility of labor between these MNCs and the rest of the economy is therefore an important mechanism for the diffusion of knowledge and technology, but these flows are not without friction. This paper analyses in great detail the flow of labor between firms with specific emphasis on flows to and from R&D intensive MNCs. Using linked employer-employee data for Denmark, we match employees moving from R&D intensive MNCs to other employees switching jobs. We find that employees are more inclined to move between R&D intensive MNCs and their subsidiaries rather than between these firms and other firms in the economy. This is particularly true for high skill employees. Our results suggest that other domestic firms are to a larger extent kept out of the 'knowledge spillover' loop, which provides them with fewer opportunities to learn from the R&D intensive MNCs. In other words, R&D intensive MNCs and their subsidiaries form a kind of sub-labor market within the national labor market; employees exhibit higher mobility within this group of firms than between this group and the rest of the labor market. [ABSTRACT FROM AUTHOR]

This article establishes a link between international differences in the organization of work and modes of regulation of labor markets within Europe. The article operates with four forms of work organization (discretionary learning, lean production, Taylorism, and simple or traditional). Through a factor analysis three dimensions of national labor market systems (flexible security, passive security, and job support) are defined. Using a multi-level logistic regression model that takes into account both characteristics of individuals and of national labor market systems it is shown that there is a significant positive correlation between flexible security and the prevalence of discretionary learning. On this basis we point to an extension of flexible security in Europe’s labor markets as an adequate response to the current crisis. [ABSTRACT FROM PUBLISHER]

Presents a study which proposed deterministic fully dynamic graph algorithms for connectivity, minimum spanning tree, 2-edge connectivity and biconnectivity. Previous work on deterministic algorithms; Discussion of the time deterministic fully dynamic algorithm for graph connectivity; Problem of decrementally maintaining a minimum spanning forest.

The variance explained by gut microbiota species was >10% for 133 metabolites and >25% for 22 metabolites, such as uremic toxin p-cresol sulfate ( I r i SP I 2 i sp = 36%) and the coffee metabolite quinate ( I r i SP I 2 i sp = 27%). The correct version replaces these sentences with 'We observed that the variance of 1168 of the 1321 metabolites was partly explained by variation in the gut microbiota (Fig. The variance explained by gut microbiota species was >15% for 554 metabolites and >30% for 61 metabolites, such as uremic toxin p-cresol sulfate ( I r i SP I 2 i sp = 46%) and the coffee metabolite quinate ( I r i SP I 2 i sp = 45%). [Extracted from the article]

Overnutrition is the principal cause of insulin resistance (IR) and dyslipidemia, which drive nonalcoholic fatty liver disease (NAFLD). Overnutrition is further linked to disrupted bowel function, microbiota alterations, and change of function in gut-lining cell populations, including Paneth cells of the small intestine. Paneth cells regulate microbial diversity through expression of antimicrobial peptides, particularly human α-defensin-5 (HD-5), and have shown repressed secretory capacity in human obesity. Mice were fed a 60% high-fat diet for 13 wk and subsequently treated with physiologically relevant amounts of HD-5 (0.001%) or vehicle for 10 wk. The glucoregulatory capacity was determined by glucose tolerance tests and measurements of corresponding insulin concentrations both before and during intervention. Gut microbiome composition was examined by 16S rRNA gene amplicon sequencing. HD-5-treated mice exhibited improved glucoregulatory capacity along with an ameliorated plasma and liver lipid profile. This was accompanied by specific decrease in jejunal inflammation and gut microbiota alterations including increased Bifidobacterium abundances, which correlated inversely with metabolic dysfunctions. This study provides proof of concept for the use of human defensins to improve host metabolism by mitigating the triad cluster of dyslipidemia, IR, and NAFLD. [ABSTRACT FROM AUTHOR]

Host ecological factors and external environmental factors are known to influence the structure of gut microbial communities, but few studies have examined the impacts of environmental changes on microbiotas in free‐ranging animals. Rapid land‐use change has the potential to shift gut microbial communities in wildlife through exposure to novel bacteria and/or by changing the availability or quality of local food resources. The consequences of such changes to host health and fitness remain unknown and may have important implications for pathogen spillover between humans and wildlife. To better understand the consequences of land‐use change on wildlife microbiotas, we analyzed long‐term dietary trends, gut microbiota composition, and innate immune function in common vampire bats (Desmodus rotundus) in two nearby sites in Belize that vary in landscape structure. We found that vampire bats living in a small forest fragment had more homogenous diets indicative of feeding on livestock and shifts in microbiota heterogeneity, but not overall composition, compared to those living in an intact forest reserve. We also found that irrespective of sampling site, vampire bats which consumed relatively more livestock showed shifts in some core bacteria compared with vampire bats which consumed relatively less livestock. The relative abundance of some core microbiota members was associated with innate immune function, suggesting that future research should consider the role of the host microbiota in immune defense and its relationship to zoonotic infection dynamics. We suggest that subsequent homogenization of diet and habitat loss through livestock rearing in the Neotropics may lead to disruption to the microbiota that could have downstream impacts on host immunity and cross‐species pathogen transmission. [ABSTRACT FROM AUTHOR]

Copyright of Applied Physiology, Nutrition & Metabolism is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Amid increasing interest in firm age and its effects on firm performance, this special issue offers an exhaustive review of the literature and a novel collection of evidence on the effects of firm age on performance, including a special focus of interest on innovation performance, financial performance, exports, survival and growth. This editorial positions the theme in the extant literature, and provides key definitions and challenges ahead in the field of evolutionary economics. It introduces the collection of articles composing the special issue. The papers offer a diversity of country contexts, as well as analytical approaches and methods. They include an exhaustive review of the literature on age and firms' performance, and present original empirical studies focusing on the effects of age on firms' economic outcomes on the one hand, and on innovation outcomes on the other hand. While most of the papers use econometric analysis, the level of analysis ranges from firm to individual. [ABSTRACT FROM AUTHOR]

We present an algorithm to support the dynamic embedding in the plane of a dynamic graph. An edge can be inserted across a face between two vertices on the face boundary (we call such a vertex pair linkable), and edges can be deleted. The planar embedding can also be changed locally by flipping components that are connected to the rest of the graph by at most two vertices. Given vertices u, v, linkable( u, v) decides whether u and v are linkable in the current embedding, and if so, returns a list of suggestions for the placement of ( u, v) in the embedding. For non-linkable vertices u, v, we define a new query, one-flip- linkable( u, v) providing a suggestion for a flip that will make them linkable if one exists. We support all updates and queries in $\mathcal {O}(\log ^{2} n)$ time. Our time bounds match those of Italiano et al. for a static (flipless) embedding of a dynamic graph. Our new algorithm is simpler, exploiting that the complement of a spanning tree of a connected plane graph is a spanning tree of the dual graph. The primal and dual trees are interpreted as having the same Euler tour, and a main idea of the new algorithm is an elegant interaction between top trees over the two trees via their common Euler tour. [ABSTRACT FROM AUTHOR]

Paracetamol/acetaminophen (N-Acetyl-p-Aminophenol; APAP) is the preferred analgesic for pain relief and fever during pregnancy. It has therefore caused concern that several studies have reported that prenatal exposure to APAP results in developmental alterations in both the reproductive tract and the brain. Genitals and nervous system of male mammals are actively masculinised during foetal development and early postnatal life by the combined actions of prostaglandins and androgens, resulting in the male-typical reproductive behaviour seen in adulthood. Both androgens and prostaglandins are known to be inhibited by APAP. Through intrauterine exposure experiments in C57BL/6 mice, we found that exposure to APAP decreased neuronal number in the sexually dimorphic nucleus (SDN) of the preoptic area (POA) in the anterior hypothalamus of male adult offspring. Likewise, exposure to the environmental pollutant and precursor of APAP, aniline, resulted in a similar reduction. Decrease in neuronal number in the SDNPOA is associated with reductions in male sexual behaviour. Consistent with the changes, male mice exposed in uteri to APAP exhibited changes in urinary marking behaviour as adults and had a less aggressive territorial display towards intruders of the same gender. Additionally, exposed males had reduced intromissions and ejaculations during mating with females in oestrus. Together, these data suggest that prenatal exposure to APAP may impair male sexual behaviour in adulthood by disrupting the sexual neurobehavioral programming. These findings add to the growing body of evidence suggesting the need to limit the widespread exposure and use of APAP by pregnant women. [ABSTRACT FROM AUTHOR]

ABSTRACT This paper analyzes what happens to redundant skills and workers when large companies close down and whether their skills are destroyed or reallocated. The analysis is based on a combination of qualitative and quantitative data of the closure of four companies. Getting a job in a skill-related industry or moving to a spinoff firm leads to skill reallocation. Thus, the result depends on regional idiosyncrasies such as industry structure and urbanization. If local policy makers and the owners exert a coordinated effort, it is possible to create success stories of less skill destruction in urban as well as peripheral regions. [ABSTRACT FROM AUTHOR]

A hallmark of parasite infection is the accumulation of innate immune cells, notably granulocytes and mast cells, at the site of infection. While this is typically viewed as a transient response, with the tissue returning to steady state once the infection is cleared, we found that mast cells accumulated in the large-intestinal epithelium following infection with the nematode Trichuris muris and persisted at this site for several months after worm expulsion. Mast cell accumulation in the epithelium was associated with the induction of type-2 immunity and appeared to be driven by increased maturation of local progenitors in the intestinal lamina propria. Furthermore, we also detected increased local and systemic levels of the mucosal mast cell protease MCPt-1, which correlated highly with the persistent epithelial mast cell population. Finally, the mast cells appeared to have striking consequences on epithelial barrier integrity, by regulation of gut permeability long after worm expulsion. These findings highlight the importance of mast cells not only in the early phases of infection but also at later stages, which has functional implications on the mucosal tissue. [ABSTRACT FROM AUTHOR]

Climate change-related coral bleaching, i.e., the visible loss of zooxanthellae from the coral host, is increasing in frequency and extent and presents a major threat to coral reefs globally. Coral bleaching has been proposed to involve accelerating light stress of their microalgal endosymbionts via a positive feedback loop of photodamage, symbiont expulsion and excess in vivo light exposure. To test this hypothesis, we used light and O2 microsensors to characterize in vivo light exposure and photosynthesis of Symbiodinium during a thermal stress experiment. We created tissue areas with different densities of Symbiodinium cells in order to understand the optical properties and light microenvironment of corals during bleaching. Our results showed that in bleached Pocillopora damicornis corals, Symbiodinium light exposure was up to fivefold enhanced relative to healthy corals, and the relationship between symbiont loss and light enhancement was well-described by a power-law function. Cell-specific rates of Symbiodinium gross photosynthesis and light respiration were enhanced in bleached P. damicornis compared to healthy corals, while areal rates of net photosynthesis decreased. Symbiodinium light exposure in Favites sp. revealed the presence of low light microniches in bleached coral tissues, suggesting that light scattering in thick coral tissues can enable photoprotection of cryptic symbionts. Our study provides evidence for the acceleration of in vivo light exposure during coral bleaching but this optical feedback mechanism differs between coral hosts. Enhanced photosynthesis in relation to accelerating light exposure shows that coral microscale optics exerts a key role on coral photophysiology and the subsequent degree of radiative stress during coral bleaching. [ABSTRACT FROM AUTHOR]

The quantitative methodology derived from replicator dynamics for empirical studies of economic evolution is becoming increasingly well developed in theory but is rarely applied in practice. One reason is the relatively naïve nature of current methods, which focus on the evolution of a single characteristic in a single environment. This assumption constrains the analysis of real selection processes in which firms operate in several markets and their products have several characteristics that interact to determine fitness. This entails that measurement of economic selection becomes confounded: characteristics that are associated with firm growth are not becoming more frequent in the population. The reason for confounded selection is that characteristics interact to augment or constrain the rate and direction of evolution and one-dimensional, single trait replicator dynamics cannot cope with confounded selection. The contribution of this paper is to develop an approach that serves to explicitly analyse confounded selection. The primary elements of the method are the selection gradients of the characteristics and the covariance matrix of the characteristics. Based on these, the method motivates a taxonomy of selection based on the interaction of characteristics. Applying the method to a population of firms will shed light on potentially confounded selection. It will reveal the indirect effects of characteristics on selection and the augmentation and constraints created thereby. [ABSTRACT FROM AUTHOR]

The notion that the obesogenic potential of high fat diets in rodents is attenuated when the protein:carbohydrate ratio is increased is largely based on studies using casein or whey as the protein source. We fed C57BL/6J mice high fat-high protein diets using casein, soy, cod, beef, chicken or pork as protein sources. Casein stood out as the most efficient in preventing weight gain and accretion of adipose mass. By contrast, mice fed diets based on pork or chicken, and to a lesser extent mice fed cod or beef protein, had increased adipose tissue mass gain relative to casein fed mice. Decreasing the protein:carbohydrate ratio in diets with casein or pork as protein sources led to accentuated fat mass accumulation. Pork fed mice were more obese than casein fed mice, and relative to casein, the pork-based feed induced substantial accumulation of fat in classic interscapular brown adipose tissue accompanied by decreased UCP1 expression. Furthermore, intake of a low fat diet with casein, but not pork, as a protein source reversed diet-induced obesity. Compared to pork, casein seems unique in maintaining the classical brown morphology in interscapular brown adipose tissue with high UCP1 expression. This was accompanied by increased expression of genes involved in a futile cycling of fatty acids. Our results demonstrate that intake of high protein diets based on other protein sources may not have similar effects, and hence, the obesity protective effect of high protein diets is clearly modulated by protein source. [ABSTRACT FROM AUTHOR]

Studies report that fetal exposure to paracetamol/acetaminophen by maternal consumption can interfere with male reproductive development. Moreover, recent biomonitoring data report widespread presence of paracetamol in German and Danish populations, suggesting exposure via secondary (nonpharmaceutical) sources, such as metabolic conversion from the ubiquitous industrial compound aniline. In this study, we investigated the extent to which paracetamol and aniline can interfere with female reproductive development. Intrauterine exposure to paracetamol by gavage of pregnant dams resulted in shortening of the anogenital distance in adult offspring, suggesting that fetal hormone signaling had been disturbed. Female offspring of paracetamol-exposed mothers had ovaries with diminished follicle reserve and reduced fertility. Fetal gonads of exposed animals had also reduced gonocyte numbers, suggesting that the reduced follicle count in adults could be due to early disruption of germ cell development. However, ex vivo cultures of ovaries from 12.5 days post coitum fetuses showed no decrease in proliferation or expression following exposure to paracetamol. This suggests that the effect of paracetamol occurs prior to this developmental stage. Accordingly, using embryonic stem cells as a proxy for primordial germ cells we show that paracetamol is an inhibitor of cellular proliferation, but without cytotoxic effects. Collectively, our data show that intrauterine exposure to paracetamol at levels commonly observed in pregnant women, as well as its precursor aniline, may block primordial germ cell proliferation, ultimately leading to reduced follicle reserves and compromised reproductive capacity later in life. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various articles within the issue on topics including market failure, importance of policy studies for policy-making process, and innovation policy in policy landscape and policy objectives.

Angiopoietin-like protein 4 (ANGPTL4) is a lipoprotein lipase inhibitor that is involved in lipid metabolism and angiogenesis. Animal studies have suggested that the ANGPTL4 protein is modulated by the gut microbiota, possibly through increased concentrations of SCFA, such as C4, found in whole-fat milk or as a result of fermentation of inulin. This study investigated whether a standardised diet either high in fat content or supplemented with inulin powder would increase plasma ANGPTL4 in overweight men and whether this increase was mediated through a compositional change of the gut microbiota. The study had a crossover design with three arms, where participants were given a standardised isoenergetic diet supplemented with inulin powder, whole-fat milk or water (control). Plasma and urine samples were collected before and after each intervention period. Faecal samples and adipose tissue biopsies were collected after each intervention period. The study included twenty-one participants of whom eighteen completed the study. The dietary interventions did not change ANGPTL4 plasma concentration, nor was plasma ANGPTL4 associated with plasma lipids, TAG or NEFA concentration. The relative abundance of bifidobacteria following the inulin diet was higher, compared with the control diet. However, the changes in microbiota were not associated with plasma ANGPTL4 and the overall composition of the microbiota did not change between the dietary periods. Although weight was maintained throughout the dietary periods, weight was negatively associated with plasma ANGPTL4 concentration. In the adipose tissue, ANGPTL4 expression was correlated with leptin expression, but not with hypoxia-inducible factor 1α (HIF-1α) expression. [ABSTRACT FROM AUTHOR]

Industrial use of aniline is increasing worldwide with production estimated to surpass 5.6 million metric tons in 2016. Exposure to aniline occurs via air, diet, and water augmenting the risk of exposing a large number of individuals. Early observations suggest that aniline is metabolized to paracetamol/acetaminophen, likely explaining the omnipresence of low concentrations of paracetamol in European populations. This is of concern as recent studies implicate paracetamol as a disrupter of reproduction. Here, we show through steroidogenic profiling that exposure to aniline led to increased levels of the D4 steroids, suggesting that the activity of CYP21 was decreased. By contrast, paracetamol decreased levels of androgens likely through inhibition of CYP17A1 activity.We confirmthat aniline in vivo is rapidly converted to paracetamol by the liver. Intrauterine exposure to aniline and paracetamol in environmental and pharmaceutical relevant doses resulted in shortening of the anogenital distance inmice, a sensitivemarker of fetal androgen levels that in humans is associated with reproductive malformations and later life reproductive disorders. In conclusion, our results provide evidence for a scenario where aniline, through its conversion into antiandrogenic paracetamol, impairsmale reproductive development. [ABSTRACT FROM AUTHOR]

The intestinal microbiota is vital for shaping the local intestinal environment as well as host immunity and metabolism. At the same time, epidemiological and experimental evidence suggest an important role for parasitic worm infections in maintaining the inflammatory and regulatory balance of the immune system. In line with this, the prevalence of persistent worm infections is inversely correlated with the incidence of immune-associated diseases, prompting the use of controlled parasite infections for therapeutic purposes. Despite this, the impact of parasite infection on the intestinal microbiota, as well as potential downstream effects on the immune system, remain largely unknown. We have assessed the influence of chronic infection with the large-intestinal nematode Trichuris muris, a close relative of the human pathogen Trichuris trichiura, on the composition of the murine intestinal microbiota by 16S ribosomal-RNA gene-based sequencing. Our results demonstrate that persistent T. muris infection dramatically affects the large-intestinal microbiota, most notably with a drop in the diversity of bacterial communities, as well as a marked increase in the relative abundance of the Lactobacillus genus. In parallel, chronic T. muris infection resulted in a significant shift in the balance between regulatory and inflammatory T cells in the intestinal adaptive immune system, in favour of inflammatory cells. Together, these data demonstrate that chronic parasite infection strongly influences the intestinal microbiota and the adaptive immune system. Our results illustrate the complex interactions between these factors in the intestinal tract, and contribute to furthering the understanding of this interplay, which is of crucial importance considering that 500 million people globally are suffering from these infections and their potential use for therapeutic purposes. [ABSTRACT FROM AUTHOR]

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This paper critically discusses the most common methodology for decomposing productivity change into inter- and intra-firm effects. It is argued that the methodology can be improved to explicitly take the role of structural transformation into account, and by so doing, a potential source of bias in the results is corrected. This requires the use of a tool from the field of theoretical evolutionary biology: Price's equation. A review of a sample of studies that apply decomposition analyses shows that the methodology is best suited for studies of the evolution of labour productivity and the reallocation of labour. Based on Danish data for 1992-2010, it is then demonstrated how the results of decomposition analyses can be considerably improved by the explicit inclusion of levels in the selection process. In the specific analysis conducted by the current paper, economic selection among industries is included. It is found that the structural transformation of the economy has a large impact on the results of decomposition studies, not least on the magnitude of the inter-firm selection effect. Structural transformation from capital-intensive and thus high-labour-productivity manufacturing towards labour-intensive and thus low-labour-productivity services entails that the traditional methodology is biased downwards in its measure of economic selection. Finally, it is demonstrated that the length of the interval studied, while often determined by data limitations, has a significant but predictable effect on the results, and it is tentatively demonstrated that economic selection tends to be stronger in the trough of the business cycle. [ABSTRACT FROM AUTHOR]

Neo-Schumpeterian evolutionary economics has, since the early works of Nelson and Winter, defined evolution as the change of the mean of a characteristic of a population. This paper trancends the previous paradigm and explores novel aspects of evolution in economics. Within the traditional paradigm change is provided by directional selection (and directional innovation). However, the full definition of evolutionary processes has to include two important types of selection that change the variance without necessarily changing the mean. Stabilizing selection removes any outlier and diversifying selection promotes the coexistence of behavioural variants. This paper emphasizes the need for an integrated analysis of all three types of selection. It also demonstrates that the evolutionary algebra provided by Price's equation increases the intellectual coherence and power of thinking about selection and other aspects of evolutionary processes. Directional, stabilizing and diversifying selection are then related to fitness functions that can produce the different types of selection; and the functions are used for simple simulations of the change of the population distribution of a quantitative characteristic. Finally, the paper adds to evolutionary economics a novel way of using Price's equation to decompose the statistics of the changes of the frequency distributions. The changes of mean, variance, skewness and kurtosis are all decomposed as the sum of a selection effect and an intra-member effect. It is especially the signs of these effects that serve to define and characterize the different types of selection. Both this result and the general analysis of the types of selection are of relevance for applied evolutionary economics. [ABSTRACT FROM AUTHOR]

Holm JB, Grygorczyk R, Lambert IH. Volume-sensitive release of organic osmolytes in the human lung epithelial cell line A549: role of the 5-lipoxygenase. Am J Physiol Cell Physiol 305: C48-C60, 2013. First published March 13, 2013; doi:10.1152/ajpcell.00412.2012.--Pathophysiological conditions challenge cell volume homeostasis and perturb cell volume regulatory mechanisms leading to alterations of cell metabolism, active transepithelial transport, cell migration, and death. We report that inhibition of the 5-lipoxygenase (5-LO) with AA861 or ETH 615-139, the cysteinyl leukotriene 1 receptor (CysLT1) with the antiasthmatic drug Zafirlukast, or the volume-sensitive organic anion channel (VSOAC) with DIDS blocks the release of organic osmolytes (taurine, meAIB) and the concomitant cell volume restoration following hypoosmotic swelling of human type II-like lung epithelial cells (A549). Reactive oxygen species (ROS) are produced in A549 cells upon hypotonic cell swelling by a diphenylene iodonium-sensitive NADPH oxidase. The swelling-induced taurine release is suppressed by ROS scavenging (butylated hydroxytoluene, N-acetyl cysteine) and potentiated by H2O2. Ca2 mobilization with ionomycin or ATP stimulates the swelling-induced taurine release whereas calmodulin inhibition (W7) inhibits the release. Chelation of the extracellular Ca2 (EGTA) had no effect on swelling-induced taurine release but prevented ATP-induced stimulation. H2O2, ATP, and ionomycin were unable to stimulate the taurine release in the presence of AA861 or Zafirlukast, placing 5-LO and CysLT1 as essential elements in the swelling-induced activation of VSOAC with ROS and Ca2 as potent modulators. Inhibition of tyrosine kinases (genistein, cucurbitacin) reduces volume-sensitive taurine release, adding tyrosine kinases (Janus kinase) as regulators of VSOAC activity. Caspase-3 activity during hypoxia is unaffected by inhibition of 5-LO/CysLT1 but reduced when swelling-induced taurine loss via VSOAC is prevented by DIDS excess extracellular taurine, indicating a beneficial role of taurine under hypoxia. [ABSTRACT FROM AUTHOR]

Platinum compounds are used in the treatment of cancer. We demonstrate that cisplatin-induced (10 μM) apoptosis (caspase-3 activity) is pronounced within 18 hours in non-adherent Ehrlich ascites tumour cells (EATC), whereas there is no increase in caspase-3 activity in the adherent Ehrlich Lettré ascites tumour cells (ELA). Loss of KCl and cell shrinkage are hallmarks in apoptosis and has been shown in EATC. However, we find no reduction in cell volume and only a minor loss of K+ which is accompanied by net uptake of Na+ following 18 hours cisplatin exposure in ELA. Glutathione and taurine have previously been demonstrated to protect cells from apoptosis. We find, however, that increase or decrease in the cellular content of glutathione and taurine has no effect on cisplatin-induced cell death in EATC and ELA. Nevertheless, knock-down of the taurine transporter TauT leads to a significant increase in apoptosis in ELA following cisplatin exposure. We find that cytosolic accumulation of cisplatin is similar in EATC and ELA. However, the nuclear accumulation and DNA-binding of cisplatin is significant lower in ELA compared to EATC. We suggest three putative reasons for the observed cisplatin insensitivity in the adherent tumor cells (ELA) compared to the non-adherent tumor cells (EATC): less nuclear cisplatin accumulation, increased TauT activity, and decreased anion and water loss. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Examines Georg W.F. Hegel's impact on Dietrich Bonhoeffer's theology by focusing on the theological similarities in method and intentions. Difficulties in tracing Hegel's impact on Bonhoeffer's 'Sanctorium Communio'; Bonhoeffer's Hegelian approach to the social sciences in 'Sanctorium Communio'; Bonhoeffer's understanding of sin and the impossibility of the Hegelian theory.

The impact of the gut microbiome is being increasingly appreciated in health and in various chronic diseases, among them neurodegenerative disorders such as Parkinson's disease (PD). In the pathogenesis of PD, the role of the gut has been previously established. In conjunction with a better understanding of the intestinal microbiome, a link to the misfolding and spread of alpha-synuclein via inflammatory processes within the gut is discussed. In a case-control study, we assessed the gut microbiome of 54 PD patients and 32 healthy controls (HC). Additionally, we tested in this proof-of-concept study whether dietary intervention alone or additional physical colon cleaning may lead to changes of the gut microbiome in PD. 16 PD patients underwent a well-controlled balanced, ovo-lacto vegetarian diet intervention including short fatty acids for 14 days. 10 of those patients received additional treatment with daily fecal enema over 8 days. Stool samples were collected before and after 14 days of intervention. In comparison to HC, we could confirm previously reported PD associated microbiome changes. The UDPRS III significantly improved and the levodopa-equivalent daily dose decreased after vegetarian diet and fecal enema in a one-year follow-up. Additionally, we observed a significant association between the gut microbiome diversity and the UPDRS III and the abundance of Ruminococcaceae. Additionally, the abundance of Clostridiaceae was significantly reduced after enema. Dietary intervention and bowel cleansing may provide an additional non-pharmacologic therapeutic option for PD patients. [ABSTRACT FROM AUTHOR]

Enteroendocrine L-cell derived peptide hormones, notably glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2), have become important targets in the treatment of type 2 diabetes, obesity and intestinal diseases. As gut microbial imbalances and maladaptive host responses have been implicated in the pathology of obesity and diabetes, this study aimed to determine the effects of pharmacologically stimulated GLP-1 and GLP-2 receptor function on the gut microbiome composition in diet-induced obese (DIO) mice. DIO mice received treatment with a selective GLP-1 receptor agonist (liraglutide, 0.2 mg/kg, BID) or dual GLP-1/GLP-2 receptor agonist (GUB09–145, 0.04 mg/kg, BID) for 4 weeks. Both compounds suppressed caloric intake, promoted a marked weight loss, improved glucose tolerance and reduced plasma cholesterol levels. 16S rDNA sequencing and deep-sequencing shotgun metagenomics was applied for comprehensive within-subject profiling of changes in gut microbiome signatures. Compared to baseline, DIO mice assumed phylogenetically similar gut bacterial compositional changes following liraglutide and GUB09-145 treatment, characterized by discrete shifts in low-abundant species and related bacterial metabolic pathways. The microbiome alterations may potentially associate to the converging biological actions of GLP-1 and GLP-2 receptor signaling on caloric intake, glucose metabolism and lipid handling. [ABSTRACT FROM AUTHOR]