Severity of cardiomyopathy associated with adenine nucleotide translocator-1 deficiency correlates with mtDNA haplogroup

Mutations of both nuclear and mitochondrial DNA (mtDNA)-encoded mitochondrial proteins can cause cardiomyopathy associated with mitochondrial dysfunction. Hence, the cardiac phenotype of nuclear DNA mitochondrial mutations might be modulated by mtDNA variation. We studied a 13-generation Mennonite pedigree with autosomal recessive myopathy and cardiomyopathy due to an SLC25A4 frameshift null mutation (c.523delC, p.Q175RfsX38), which codes for the heart-muscle isoform of the adenine nucleotide translocator-1. Ten homozygous null (adenine nucleotide translocator-1(-/-)) patients monitored over a median of 6 years had a phenotype of progressive myocardial thickening, hyperalaninemia, lactic acidosis, exercise intolerance, and persistent adrenergic activation. Electrocardiography and echocardiography with velocity vector imaging revealed abnormal contractile mechanics, myocardial repolarization abnormalities, and impaired left ventricular relaxation. End-stage heart disease was characterized by massive, symmetric, concentric cardiac hypertrophy; widespread cardiomyocyte degeneration; overabundant and structurally abnormal mitochondria; extensive subendocardial interstitial fibrosis; and marked hypertrophy of arteriolar smooth muscle. Substantial variability in the progression and severity of heart disease segregated with maternal lineage, and sequencing of mtDNA from five maternal lineages revealed two major European haplogroups, U and H. Patients with the haplogroup U mtDNAs had more rapid and severe cardiomyopathy than those with haplogroup H

Evolution of the latitudinal diversity gradient in the hyperdiverse ant genus Pheidole

AimThe latitudinal diversity gradient is the dominant geographic pattern of life on Earth, but a consensus understanding of its origins has remained elusive. The analysis of recently diverged, hyperâ rich invertebrate groups provides an opportunity to investigate latitudinal patterns with the statistical power of large trees while minimizing potentially confounding variation in ecology and history. Here, we synthesize global phylogenetic and macroecological data on a hyperdiverse (> 1,100 species) ant radiation, Pheidole and test predictions of three general explanations for the latitudinal gradient: variation in diversification rates, tropical conservatism and ecological regulation.LocationGlobal.Time periodThe past 35 million years.Major taxa studiedThe hyperdiverse ant genus Pheidole Westwood.MethodsWe assembled geographic data for 1,499 species and morphospecies, and inferred a dated phylogeny for 449 species of Pheidole, including 167 species newly sequenced for this study. We tested for correlations between diversification rate and latitude with Bayesian analysis of macroevolutionary mixtures (BAMM), hidden state speciation and extinction (HiSSE), geographic state speciation and extinction (GeoSSE), and a nonâ parametric method (FiSSE), evaluated evidence for richness steady state, and examined patterns of diversification as Pheidole spread around the globe.ResultsThere was no evidence of systematic variation of net diversification rates with latitude across any of the methods. We found that Pheidole diversification occurred in bursts when new continents were colonized, followed by a slowdown in each region, but there is no evidence richness has saturated at an equilibrium in any region. Additionally, we found latitudinal affinity is moderately conserved with a Neotropical ancestor and simulations show that phylogenetic inertia alone is sufficient to produce the gradient pattern.Main conclusionsOur results provide no evidence that diversification rates vary systematically with latitude. Richness is far from steady state in each region, contrary to the ecological regulation hypothesis, although there is evidence that ecological opportunity promotes diversification after colonization of new areas. The fact that niche conservatism is strong enough to produce the gradient pattern is in accord with the tropical conservatism hypothesis. Overall, these results shed light on the mechanisms underlying the emergence of the diversity gradient within the past 34 million years, complementing recent work on deeper timeâ scales, and more generally contribute toward muchâ needed invertebrate perspective on global biodiversity dynamics.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148253/1/geb12867-sup-0001-AppendixS1-S2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148253/2/geb12867-sup-0005-TableS3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148253/3/geb12867-sup-0006-Supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148253/4/geb12867-sup-0002-FigS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148253/5/geb12867.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148253/6/geb12867_am.pd

Beginning of the End of Cost Competitiveness in CEE Countries - Analysis of Dependence between Labor Costs and Internationalization of the Region

In order to exemplify the above econometric model I carried out empirical analysis of the companies listed on the Warsaw Stock Exchange, identifying the companies for which efficiency-seeking is the main internationalization motive. The analysis of internationalization of 26 companies during the years 1990-2010 clearly shows that a significant part of investments is located outside the territory of Poland, in the countries with lower labor costs. This fact confirms that CEE countries will gradually become less and less attractive in terms of costs not only for MNEs from developed countries but also for the companies originating from transition economies.Głównym celem artykułu jest weryfikacja, czy niski poziom kosztów pracy w Europie Środkowej i Wschodniej będący do tej pory jednym z czynników wpływających na konkurencyjność tego regionu pozostanie nim w dłuższej perspektywie czasowej. W pracy na podstawie próby wszystkich państw UE zbadano zależność pomiędzy poziomem internacjonalizacji (stan odpływu BIZ per capita) a kosztami pracy w sektorze przedsiębiorstw i GNP per capita. Analiza regresji potwierdziła istnienie zależności pomiędzy wyżej wymienionymi czynnikami. Oznacza to, że stopniowy wzrost kosztów pracy w państwach Europy Środkowej i Wschodniej prowadził będzie do stopniowego odpływu BIZ z tego regionu do państw bardziej konkurencyjnych kosztowo. W celu egzemplifikacji powyższych zależności w pracy dodatkowo przedstawiono analizę inwestycji zagranicznych polskich spółek notowanych na GPW, z których to 26 dokonało inwwestycji zagranicznych o wyraźnych motywach związanych z obniżeniem kosztów produkcji. Fakt ten potwierdza powolny spadek konkurencyjności kosztowej polskiej gospodarki, tym samym zmusza do poszukiwania nowych rozwiązań instytucjonalnych mogących utrzymać konkurencyjność polskiej gospodarki w długim okresie

Association of ultra-processed food intake with risk of inflammatory bowel disease: Prospective cohort study

Objective: To evaluate the relation between intake of ultra-processed food and risk of inflammatory bowel disease (IBD).Design: Prospective cohort study.Setting: 21 low, middle, and high income countries across seven geographical regions (Europe and North America, South America, Africa, Middle East, south Asia, South East Asia, and China).Participants: 116 087 adults aged 35-70 years with at least one cycle of follow-up and complete baseline food frequency questionnaire (FFQ) data (country specific validated FFQs were used to document baseline dietary intake). Participants were followed prospectively at least every three years.Main outcome measures: The main outcome was development of IBD, including Crohn\u27s disease or ulcerative colitis. Associations between ultra-processed food intake and risk of IBD were assessed using Cox proportional hazard multivariable models. Results are presented as hazard ratios with 95% confidence intervals.Results: Participants were enrolled in the study between 2003 and 2016. During the median follow-up of 9.7 years (interquartile range 8.9-11.2 years), 467 participants developed incident IBD (90 with Crohn\u27s disease and 377 with ulcerative colitis). After adjustment for potential confounding factors, higher intake of ultra-processed food was associated with a higher risk of incident IBD (hazard ratio 1.82, 95% confidence interval 1.22 to 2.72 for ≥5 servings/day and 1.67, 1.18 to 2.37 for 1-4 servings/day compared with \u3c1 serving/day, P=0.006 for trend). Different subgroups of ultra-processed food, including soft drinks, refined sweetened foods, salty snacks, and processed meat, each were associated with higher hazard ratios for IBD. Results were consistent for Crohn\u27s disease and ulcerative colitis with low heterogeneity. Intakes of white meat, red meat, dairy, starch, and fruit, vegetables, and legumes were not associated with incident IBD.Conclusions: Higher intake of ultra-processed food was positively associated with risk of IBD. Further studies are needed to identify the contributory factors within ultra-processed foods.Study registration: ClinicalTrials.gov NCT03225586

What lies between market and hierarchy? Insights from internalization theory and global value chain theory

In this paper, we suggest that internalization theory might be extended by incorporating complementary insights from GVC theory. More specifically, we argue that internalization theory can explain why lead firms might wish to externalize selected activities, but that it is largely silent on the mechanisms by which those lead firms might exercise control over the resultant externalized relationships with their GVC partners. We advance an explanation linking the choice of control mechanism to two factors: power asymmetries between the lead firms and their GVC partners, and the degree of codifiability of the information to be exchanged in the relationship

Socially Parasitic Ants Evolve a Mosaic of Host-Matching and Parasitic Morphological Traits

A basic expectation of evolution by natural selection is that species morphologies will adapt to their ecological niche. In social organisms, this may include selective pressure from the social environment. Many nonant parasites of ant colonies are known to mimic the morphology of their host species, often in striking fashion [1, 2], indicating there is selection on parasite morphology to match the host (Batesian and/or Wasmannian mimicry [3]). However, ants that parasitize other ant societies are usually closely related to their hosts (Emery’s rule) [4–8] and expected to be similar due to common ancestry, making any kind of mimicry difficult to detect [9]. Here, we investigate the diversification of the hyperdiverse ant genus Pheidole in Madagascar, including the evolution of 13 putative social parasite species within a broader radiation of over 100 ant species on the island. We find that the parasitic species are monophyletic and that their associated hosts are spread across the Malagasy Pheidole radiation. This provides an opportunity to test for selection on morphological similarity and divergence between parasites and hosts. Using X-ray microtomography and both linear measurements and three-dimensional (3D) geometric morphometrics, we show that ant social parasite worker morphologies feature a mix of ‘‘host-matching’’ and ‘‘parasitic’’ traits, where the former converge on the host phenotype and the latter diverge from typical Pheidole phenotypes to match a common parasitic syndrome. This finding highlights the role of social context in shaping the evolution of phenotypes and raises questions about the role of morphological sensing in nestmate recognition.All fieldwork was funded by National Science Foundation grants DEB0072713, DEB-0344731, and DEB-0842395 (to B.L.F.). Lab work was supported by a National Science Foundation grant (DEB-1145989) (to E.P.E. and L.L.K.) and subsidy funding to OIS

Funerary Artifacts, Social Status, and Atherosclerosis in Ancient Peruvian Mummy Bundles

Background: Evidence of atherosclerotic plaques in ancient populations has led to the reconsideration of risk factors for heart disease and of the common belief that it is a disease of modern times. Methods: Fifty-one wrapped mummy bundles excavated from the sites of Huallamarca, Pedreros, and Rinconada La Molina from the Puruchuco Museum collection in Lima, Peru, were scanned using computed tomography to investigate the presence of atherosclerosis. Funerary artifacts contained within the undisturbed mummy bundles were analyzed as an attempt to infer the social status of the individuals to correlate social status with evidence of heart disease in this ancient Peruvian group. This work also provides an inventory of the museum mummy collection to guide and facilitate future research. Results: Statistical analysis concluded that there is little association between the types of grave goods contained within the bundles when the groups are pooled together. However, some patterns of artifact type, material, atherosclerosis, and sex emerge when the 3 excavation sites are analyzed separately. Conclusions: From the current sample, it would seem that social class is difficult to discern, but those from Huallamarca have the most markers of elite status. We had hypothesized that higher-status individuals may have had lifestyles that would place them at a higher risk for atherogenesis. There seems to be some indication of this within the site of Huallamarca, but it is inconclusive in the other 2 archeological sites. It is possible that a larger sample size in the future could reveal more statistically significant results

Genomic Correlates of Atherosclerosis in Ancient Humans

Paleogenetics offers a unique opportunity to study human evolution, population dynamics, and disease evolution in situ. Although histologic and computed x-ray tomographic investigations of ancient mummies have clearly shown that atherosclerosis has been present in humans for more than 5,000 years, limited data are available on the presence of genetic predisposition for cardiovascular disease in ancient human populations. In a previous whole-genome study of the Tyrolean Iceman, a 5,300-year-old glacier mummy from the Alps, an increased risk for coronary heart disease was detected. The Iceman’s genome revealed several single nucleotide polymorphisms that are linked with cardiovascular disease in genome-wide association studies. Future genetic studies of ancient humans from various geographic origins and time periods have the potential to provide more insights into the presence and possible changes of genetic risk factors in our ancestors. The study of ancient humans and a better understanding of the interaction between environmental and genetic influences on the development of heart diseases may lead to a more effective prevention and treatment of the most common cause of death in the modern world

How do MNC R&D laboratory roles affect employee international assignments?

Research and development (R&D) employees are important human resources for multinational corporations (MNCs) as they are the driving force behind the advancement of innovative ideas and products. International assignments of these employees can be a unique way to upgrade their expertise; allowing them to effectively recombine their unique human resources to progress existing knowledge and advance new ones. This study aims to investigate the effect of the roles of R&D laboratories in which these employees work on the international assignments they undertake. We categorise R&D laboratory roles into those of the support laboratory, the locally integrated laboratory and the internationally interdependent laboratory. Based on the theory of resource recombinations, we hypothesise that R&D employees in support laboratories are not likely to assume international assignments, whereas those in locally integrated and internationally interdependent laboratories are likely to assume international assignments. The empirical evidence, which draws from research conducted on 559 professionals in 66 MNC subsidiaries based in Greece, provides support to our hypotheses. The resource recombinations theory that extends the resource based view can effectively illuminate the international assignment field. Also, research may provide more emphasis on the close work context of R&D scientists rather than analyse their demographic characteristics, the latter being the focus of scholarly practice hitherto