| 1. |
- Benrick, Anna, 1979, et al.
(author)
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Adiponectin protects against development of metabolic disturbances in a PCOS mouse model
- 2017
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 114:34
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Journal article (peer-reviewed)abstract
- Adiponectin, together with adipocyte size, is the strongest factor associated with insulin resistance in women with polycystic ovary syndrome (PCOS). This study investigates the causal relationship between adiponectin levels and metabolic and reproductive functions in PCOS. Prepubertal mice overexpressing adiponectin from adipose tissue (APNtg), adiponectin knockouts (APNko), and their wild-type (WT) littermate mice were continuously exposed to placebo or dihydrotestosterone (DHT) to induce PCOS-like traits. As expected, DHT exposure led to reproductive dysfunction, as judged by continuous anestrus, smaller ovaries with a decreased number of corpus luteum, and an increased number of cystic/atretic follicles. A two-way between-groups analysis showed that there was a significant main effect for DHT exposure, but not for genotype, indicating adiponectin does not influence follicle development. Adiponectin had, however, some protective effects on ovarian function. Similar to in many women with PCOS, DHT exposure led to reduced adiponectin levels, larger adipocyte size, and reduced insulin sensitivity in WTs. APNtg mice remained metabolically healthy despite DHT exposure, while APNko-DHT mice were even more insulin resistant than their DHT-exposed littermate WTs. DHT exposure also reduced the mRNA expression of genes involved in metabolic pathways in gonadal adipose tissue of WT and APNko, but this effect of DHT was not observed in APNtg mice. Moreover, APNtg-DHT mice displayed increased pancreatic mRNA levels of insulin receptors, Pdx1 and Igf1R, suggesting adiponectin stimulates beta cell viability/hyperplasia in the context of PCOS. In conclusion, adiponectin improves metabolic health but has only minor effects on reproductive functions in this PCOS-like mouse model.
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| 2. |
- Cohen, Joel E., et al.
(author)
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Body sizes of hosts and parasitoids in individual feeding relationships
- 2005
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In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 102:3, s. 684-689
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Journal article (peer-reviewed)abstract
- In a natural community of 49 species (12 species of aphids and 37 species of their parasitoids), body lengths of 2,151 parasitoid individuals were, to an excellent approximation, related to the body lengths of their individual aphid hosts by a power law with an exponent close to 3/4. Two alternative models predict this exponent. One is based on surface area to volume relationships. The other is based on recent developments in metabolic ecology. Both models require a changing ratio (in both host and parasitoid) of length to diameter with increasing body length. These changing ratios are manifested differently in the two models and result in testably different predictions for the scaling of body form with increasing size. The estimated exponent of 3/4 for the relationship between individual host body size and individual parasitoid body size degrades to an exponent of nearly 1/2, and the scatter in the relationship between aphid and parasitoid body length is substantially increased, if the average length of a parasitoid species is examined as a function of the average length of its aphid host species instead of using measurements of individuals.allometry | aphids | development | metabolism | weight–length relationsExplaining the size of organisms is an enduring challenge to ecologists and evolutionary biologists (1, 2) to cellular and developmental biologists (3). Ecological studies of the relationship between consumer and resource body sizes (4–8) usually assume that the average body size of a species is an adequate approximation to the size of the individuals taking part in a particular trophic interaction. However, individuals of different size within one resource species may be selectively consumed by different consumer species or individuals of different size within a given consumer species. Vice versa, individuals of different size within one consumer species may selectively consume resource species of different average size or individuals of different size within a given resource species. To understand the relationship between consumer and resource body sizes, it is important that the data correctly represent the body sizes of the consumers and resources involved in the trophic interactions. What are the consequences of focusing on body sizes of consumer and resource individuals vs. average sizes of taxonomic species for understanding feeding relations in natural communities? To answer this question, here we report quantitative field data on body sizes in individual events of parasitism.Animal consumers are often considerably larger than their prey (4), whereas parasites and pathogens are generally much smaller than their resources (5). Solitary insect parasitoids that complete their larval development on or in the body of other living insects, and require just a single host to complete development, lie between these extremes: they are often similar in size to their insect hosts. Parasitoid and host body sizes are well suited to shed light on the role of individual differences in consumer-resource body size relations because the variations in both parasitoid and host body sizes are likely to be of comparable magnitude.Parasitoids are important components of all terrestrial ecological communities. Probably 1–2 million species are parasitoids (9), and they are thus a significant fraction of all species on this planet. As potentially important regulators of their host populations, parasitoids are intensively used in biological control (10). Most prior studies of the body sizes of hosts and parasitoids consider only a single species of host. The few studies (11–14) that consider host–parasitoid size relationships of multiple species have only one data point per species.We studied quantitatively the relationship between final individual aphid host and parasitoid body length in a natural aphid-parasitoid community with multiple species of hosts and parasitoids. The objectives of the study were to (i) describe the relationship between final aphid host and parasitoid body size, (ii) analyze the consequences of focusing on body sizes of consumer and resource individuals vs. average sizes of taxonomic species for the apparent relationship between final aphid host and parasitoid body size, and (iii) offer two alternative explanations for the relationship between final aphid host and parasitoid body size. We hope that future studies will discriminate between these alternative explanations.
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| 3. |
- Cohen, Joel, et al.
(author)
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Ecological community description using the food web, species abundance, and body size
- 2003
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In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 100:4, s. 1781-1786
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Journal article (peer-reviewed)abstract
- Measuring the numerical abundance and average body size of individuals of each species in an ecological community's food web reveals new patterns and illuminates old ones. This approach is illustrated using data from the pelagic community of a small lake: Tuesday Lake, Michigan, United States. Body mass varies almost 12 orders of magnitude. Numerical abundance varies almost 10 orders of magnitude. Biomass abundance (average body mass times numerical abundance) varies only 5 orders of magnitude. A new food web graph, which plots species and trophic links in the plane spanned by body mass and numerical abundance, illustrates the nearly inverse relationship between body mass and numerical abundance, as well as the pattern of energy flow in the community. Species with small average body mass occur low in the food web of Tuesday Lake and are numerically abundant. Larger-bodied species occur higher in the food web and are numerically rarer. Average body size explains more of the variation in numerical abundance than does trophic height. The trivariate description of an ecological community by using the food web, average body sizes, and numerical abundance includes many well studied bivariate and univariate relationships based on subsets of these three variables. We are not aware of any single community for which all of these relationships have been analyzed simultaneously. Our approach demonstrates the connectedness of ecological patterns traditionally treated as independent. Moreover, knowing the food web gives new insight into the disputed form of the allometric relationship between body mass and abundance.
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| 4. |
- Dahl-Halvarsson, Martin, et al.
(author)
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Drosophila model of myosin myopathy rescued by overexpression of a TRIM-protein family member
- 2018
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:28
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Journal article (peer-reviewed)abstract
- Myosin is a molecular motor indispensable for body movement and heart contractility. Apart from pure cardiomyopathy, mutations in MYH7 encoding slow/beta-cardiac myosin heavy chain also cause skeletal muscle disease with or without cardiac involvement. Mutations within the alpha-helical rod domain of MYH7 are mainly associated with Laing distal myopathy. To investigate the mechanisms underlying the pathology of the recurrent causative MYH7 mutation (K1729del), we have developed a Drosophila melanogaster model of Laing distal myopathy by genomic engineering of the Drosophila Mhc locus. Homozygous MhcK1728del animals die during larval/pupal stages, and both homozygous and heterozygous larvae display reduced muscle function. Flies expressing only MhcK1728del in indirect flight and jump muscles, and heterozygous MhcK1728del animals, were flightless, with reduced movement and decreased lifespan. Sarcomeres of MhcK1728del mutant indirect flight muscles and larval body wall muscles were disrupted with clearly disorganized muscle filaments. Homozygous MhcK1728del larvae also demonstrated structural and functional impairments in heart muscle, which were not observed in heterozygous animals, indicating a dose-dependent effect of the mutated allele. The impaired jump and flight ability and the myopathy of indirect flight and leg muscles associated with MhcK1728del were fully suppressed by expression of Abba/Thin, an E3-ligase that is essential for maintaining sarcomere integrity. This model of Laing distal myopathy in Drosophila recapitulates certain morphological phenotypic features seen in Laing distal myopathy patients with the recurrent K1729del mutation. Our observations that Abba/Thin modulates these phenotypes suggest that manipulation of Abba/Thin activity levels may be beneficial in Laing distal myopathy.
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| 5. |
- Ericsson, Malin, et al.
(author)
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Childhood social class and cognitive aging in the Swedish Adoption/Twin Study of Aging
- 2017
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In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 114:27, s. 7001-7006
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Journal article (peer-reviewed)abstract
- In this report we analyzed genetically informative data to investigate within-person change and between-person differences in late-life cognitive abilities as a function of childhood social class. We used data from nine testing occasions spanning 28 y in the Swedish Adoption/Twin Study of Aging and parental social class based on the Swedish socioeconomic index. Cognitive ability included a general factor and the four domains of verbal, fluid, memory, and perceptual speed. Latent growth curve models of the longitudinal data tested whether level and change in cognitive performance differed as a function of childhood social class. Between-within twin-pair analyses were performed on twins reared apart to assess familial confounding. Childhood social class was significantly associated with mean-level cognitive performance at age 65 y, but not with rate of cognitive change. The association decreased in magnitude but remained significant after adjustments for level of education and the degree to which the rearing family was supportive toward education. A between-pair effect of childhood social class was significant in all cognitive domains, whereas within-pair estimates were attenuated, indicating genetic confounding. Thus, childhood social class is important for cognitive performance in adulthood on a population level, but the association is largely attributable to genetic influences.
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| 6. |
- Fernandes, Ricardo A., et al.
(author)
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A cell topography-based mechanism for ligand discrimination by the T cell receptor
- 2019
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In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:28, s. 14002-14010
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Journal article (peer-reviewed)abstract
- The T cell receptor (TCR) initiates the elimination of pathogens and tumors by T cells. To avoid damage to the host, the receptor must be capable of discriminating between wild-type and mutated self and nonself peptide ligands presented by host cells. Exactly how the TCR does this is unknown. In resting T cells, the TCR is largely unphosphorylated due to the dominance of phosphatases over the kinases expressed at the cell surface. However, when agonist peptides are presented to the TCR by major histocompatibility complex proteins expressed by antigen-presenting cells (APCs), very fast receptor triggering, i.e., TCR phosphorylation, occurs. Recent work suggests that this depends on the local exclusion of the phosphatases from regions of contact of the T cells with the APCs. Here, we developed and tested a quantitative treatment of receptor triggering reliant only on TCR dwell time in phosphatase-depleted cell contacts constrained in area by cell topography. Using the model and experimentally derived parameters, we found that ligand discrimination likely depends crucially on individual contacts being ∼200 nm in radius, matching the dimensions of the surface protrusions used by T cells to interrogate their targets. The model not only correctly predicted the relative signaling potencies of known agonists and nonagonists but also achieved this in the absence of kinetic proofreading. Our work provides a simple, quantitative, and predictive molecular framework for understanding why TCR triggering is so selective and fast and reveals that, for some receptors, cell topography likely influences signaling outcomes.
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| 7. |
- Nalepka, Patrick, et al.
(author)
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Human social motor solutions for human-machine interaction in dynamical task contexts
- 2019
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In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:4, s. 1437-1446
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Journal article (peer-reviewed)abstract
- Multiagent activity is commonplace in everyday life and can improve the behavioral efficiency of task performance and learning. Thus, augmenting social contexts with the use of interactive virtual and robotic agents is of great interest across health, sport, and industry domains. However, the effectiveness of human–machine interaction (HMI) to effectively train humans for future social encounters depends on the ability of artificial agents to respond to human coactors in a natural, human-like manner. One way to achieve effective HMI is by developing dynamical models utilizing dynamical motor primitives (DMPs) of human multiagent coordination that not only capture the behavioral dynamics of successful human performance but also, provide a tractable control architecture for computerized agents. Previous research has demonstrated how DMPs can successfully capture human-like dynamics of simple nonsocial, single-actor movements. However, it is unclear whether DMPs can be used to model more complex multiagent task scenarios. This study tested this human-centered approach to HMI using a complex dyadic shepherding task, in which pairs of coacting agents had to work together to corral and contain small herds of virtual sheep. Human–human and human–artificial agent dyads were tested across two different task contexts. The results revealed (i) that the performance of human–human dyads was equivalent to those composed of a human and the artificial agent and (ii) that, using a “Turing-like†methodology, most participants in the HMI condition were unaware that they were working alongside an artificial agent, further validating the isomorphism of human and artificial agent behavior.
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