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Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
With rapid urbanization worldwide, most people now live in cities, but the effects of urbanization on knowledge about the natural environment is not well studied. Due to the importance of Cymbidium to Chinese traditional culture, we tested how urbanization influences the distribution of orchid knowledge across various knowledge domains at risk of loss due to declining orchid populations. Participants in the Cymbidium trade were interviewed in three distinct urbanization-level jurisdictions in Sichuan, China: Puge (low urbanization), Huili (moderate urbanization) and Chengdu (high urbanization). Using photographic cue-cards of nine Cymbidium taxa, we assessed aggregate and specific knowledge held by 91 orchid collectors/traders across the urbanization gradient. Contrary to expectations, we found that urbanization and orchid knowledge were positively related, but this varied by knowledge type, with moderate urbanization showing significantly higher knowledge in two domains. Our findings suggest that a generalizable understanding of how urbanization affects knowledge must account for differences in knowledge types and geographic/cultural scales, with implications for biocultural diversity conservation in an increasingly urban world.
For decades, fructose intake has been recognized as an environmental risk for metabolic syndromes and diseases. Here, we comprehensively examined effects of fructose intake on mice liver transcriptomes. Fructose supplemented water (34%; wt/vol) was fed to both male and female C57BL/6N mice at their free will for six weeks, followed by hepatic transcriptomics analysis. Based on our criteria, differentially expressed genes (DEGs) were selected and subjected to further computational analyses to predict key pathways and upstream regulator(s). Subsequently, predicted genes and pathways from the transcriptomics dataset were validated via quantitative RT-PCR analyses. As results, we identified 89 down-regulated and 88 up-regulated mRNAs in fructose-fed mice livers. These DEGs were subjected to bioinformatic analysis tools in which DEGs were mainly enriched in xenobiotic metabolic processes; further, in the Ingenuity Pathway Analysis software, it was suggested that the aryl hydrocarbon receptor (AhR) is an upstream regulator governing overall changes, while fructose suppresses the AhR signaling pathway. In our quantitative RT-PCR validation, we confirmed that fructose suppressed AhR signaling through modulating expressions of transcription factor (Arnt) and upstream regulators (Ncor2, and Rb1). Altogether, we demonstrated that ad libitum fructose intake suppresses the canonical AhR signaling pathway in C57BL/6N mice liver. Based on our current observations, further studies are warranted, especially with regard to the effects of co-exposure to fructose on 1) other types of carcinogens and 2) inflammation inducing agents (or even diets such as a high-fat diet), to find implications of fructose induced-AhR suppression.
Given the vast superiority of synchrotron radiation sources for EXAFS and near-edge measurements, one might assume that conducting such experiments in the laboratory is a waste of time and resources. Upon more careful consideration of the realities of everyday research, however, one can easily see that this is not true. In fact, many people have come to this realization, so much so that a whole conference has been devoted to laboratory EXAFS facilities, their role in research and their relation to synchrotron facilities. The concensus after the conference was that laboratory instruments can and have been developed, with adequate performance for a variety of nontrivial experiments. They usually employ dedicated focusing spectrometers, rotating anode generators and fairly expensive monochromator crystals (see articles in ref. 1 and 2).
Generalized direct products with amalgamated subgroups were introduced by B. H. Neumann and Hanna Neumann in their joint paper (4). In general, we call a given collection of groups with specified subgroups amalgamated an amalgam of groups; if all groups are abelian we speak of an abelian amalgam. The group freely generated by the amalgam is called the abelian free sum of the amalgam provided it contains the amalgam isomorphically. The free abelian sum need not exist. Hence one of the problems is to find necessary and sufficient conditions for its existence.
Sufficient amino acid (AA) transport is essential to ensure the normal physiological function and growth of growing animals. The processes of AA sensing and transport in humans and murine animals, but rarely in goats, have been arousing great interest recently. This study was conducted to investigate the messenger RNA expression patterns of lysophosphatidic acid receptor 5 (LPAR5), guanine nucleotide-binding protein α-transducing 3 (GNAT3) and important partial AA transporters in digestive tracts, metabolic organs and muscles of growing goats. The results showed that these genes were widely expressed in goats, and had different expression patterns. LPAR5, GNAT3, solute carrier (SLC38A2), SLC7A7, SLC7A1 and SLC3A1 were rarely expressed in the rumen, but were highly expressed in the abomasum and intestine which are the main sites of AA absorption. GNAT3, SLC38A1, SLC38A2, SLC6A19, SLC7A7 and SLC7A1 showed comparatively high expression in the pancreas and the vital digestive glands, and the relatively high expression of these nine genes were noted in the tibialis posterior, the active muscle in energy metabolism. The correlation analysis showed that there were certain positive correlation among most genes. The current results indicate that the AA sensing and transport occur extensively in the abomasum and small intestine, metabolic organs and muscle tissues of ruminants, and that related genes have tissue specificity.
The response of soil microbial communities to soil quality changes is a sensitive indicator of soil ecosystem health. The current work investigated soil microbial communities under different fertilization treatments in a 31-year experiment using the phospholipid fatty acid (PLFA) profile method. The experiment consisted of five fertilization treatments: without fertilizer input (CK), chemical fertilizer alone (MF), rice (Oryza sativa L.) straw residue and chemical fertilizer (RF), low manure rate and chemical fertilizer (LOM), and high manure rate and chemical fertilizer (HOM). Soil samples were collected from the plough layer and results indicated that the content of PLFAs were increased in all fertilization treatments compared with the control. The iC15:0 fatty acids increased significantly in MF treatment but decreased in RF, LOM and HOM, while aC15:0 fatty acids increased in these three treatments. Principal component (PC) analysis was conducted to determine factors defining soil microbial community structure using the 21 PLFAs detected in all treatments: the first and second PCs explained 89.8% of the total variance. All unsaturated and cyclopropyl PLFAs except C12:0 and C15:0 were highly weighted on the first PC. The first and second PC also explained 87.1% of the total variance among all fertilization treatments. There was no difference in the first and second PC between RF and HOM treatments. The results indicated that long-term combined application of straw residue or organic manure with chemical fertilizer practices improved soil microbial community structure more than the mineral fertilizer treatment in double-cropped paddy fields in Southern China.
In this paper, the melting of stainless steel 316L using Computational Fluid Dynamics to observe the melt pool characteristics is studied. The simulation model allows the observation of the molten pool flow during the selective laser melting process due to Marangoni's effect and recoil pressure. Furthermore, different parameters are tested to show their effects on the melt pool and track formation. Different laser powers, as well as scanning speeds, were used to study the effects they have on the melt pool characteristics. The results were used to determine the relationships between these factors and the melt pool characteristics.
The gastrointestinal tract (GIT) of animals is capable of sensing various kinds of nutrients via G-protein coupled receptor-mediated signaling transduction pathways, and the process is known as ‘gut nutrient chemosensing’. GPR40, GPR41, GPR43 and GPR119 are chemoreceptors for free fatty acids (FFAs) and lipid derivatives, but they are not well studied in small ruminants. The objective of this study is to determine the expression of GPR40, GPR41, GPR43 and GPR119 along the GIT of kid goats under supplemental feeding (S) v. grazing (G) during early development. In total, 44 kid goats (initial weight 1.35±0.12 kg) were slaughtered for sampling (rumen, abomasum, duodenum, jejunum, ileum, cecum, colon and rectum) between days 0 and 70. The expression of GPR41 and GPR43 were measured at both mRNA and protein levels, whereas GPR40 and GPR119 were assayed at protein level only. The effects of age and feeding system on their expression were variable depending upon GIT segments, chemoreceptors and expression level (mRNA or protein), and sometimes feeding system × age interactions (P<0.05) were observed. Supplemental feeding enhanced expression of GPR40, GPR41 and GPR43 in most segments of the GIT of goats, whereas G enhanced expression of GPR119. GPR41 and GPR43 were mainly expressed in rumen, abomasum and cecum, with different responses to age and feeding system. GPR41 and GPR43 expression in abomasum at mRNA level was greatly (P<0.01) affected by both age and feeding system; whereas their expression in rumen and abomasum at protein level were different, feeding system greatly (P<0.05) affected GPR41 expression, but had no effect (P>0.05) on GPR43 expression; and there were no feeding system×age interactions (P>0.05) on GPR41 and GPR43 protein expression. The expression of GPR41 and GPR43 in rumen and abomasum linearly (P<0.01) increased with increasing age (from days 0 to 70). Meanwhile, age was the main factor affecting GPR40 expression throughout the GIT. These outcomes indicate that age and feeding system are the two factors affecting chemoreceptors for FFAs and lipid derivatives expression in the GIT of kids goats, and S enhanced the expression of chemoreceptors for FFAs, whereas G gave rise to greater expression of chemoreceptors for lipid derivatives. Our results suggest that enhanced expression of chemoreceptors for FFAs might be one of the benefits of early supplemental feeding offered to young ruminants during early development.
We introduce the polygonalisation complex of a surface, a cube complex whose vertices correspond to polygonalisations. This is a geometric model for the mapping class group and it is motivated by works of Harer, Mosher and Penner. Using properties of the flip graph, we show that the midcubes in the polygonalisation complex can be extended to a family of embedded and separating hyperplanes, parametrised by the arcs in the surface.
We study the crossing graph of these hyperplanes and prove that it is quasi-isometric to the arc complex. We use the crossing graph to prove that, generically, different surfaces have different polygonalisation complexes. The polygonalisation complex is not CAT(0), but we can characterise the vertices where Gromov's link condition fails. This gives a tool for proving that, generically, the automorphism group of the polygonalisation complex is the (extended) mapping class group of the surface.
Introduction: Accurate identification of children with a concussion by emergency department (ED) physicians is important to initiate appropriate anticipatory guidance and management. In children meeting international criteria for concussion, we aimed to determine the proportion who were provided this diagnosis by the ED physician and which variables were associated with a physician-diagnosed concussion. We also compared persistent symptoms in concussion cases versus those with alternative diagnoses. Methods: This was a planned secondary analysis of a prospective, multicenter cohort study. Participants were children aged 5 through 17 years and met Zurich/Berlin International Consensus Statement criteria for concussion. The primary outcome was the proportion of study participants who were assigned a diagnosis of concussion by the treating ED physician. Based on available evidence, between 50% and 90% of children meeting international concussion criteria are also diagnosed by an ED physician as having a concussion. Assuming a worst case scenario that 50% of physicians would diagnose concussion, our anticipated study sample size of 2946 would be accompanied by a +2% margin of error at the 95% confidence level for the primary outcome. Results: Among the 2946 eligible children, 2340 [79.4% (95% CI 78.0, 80.8)] were diagnosed with a concussion by an ED physician. Twelve variables were associated with this ED diagnosis, five of which had an odds ratio (OR) > 1.5: older age (13-17 vs 5-7 years, OR=2.9), longer time to presentation (>16 vs. <16 hours, OR=2.1), nausea (OR=1.7), sport mechanism (OR=1.7), and amnesia (OR=1.6). In those with physician-diagnosed concussion versus no concussion, the frequency of persistent symptoms was 62.5% vs. 38.8% (p<0.0001) at one week, 46.3% vs. 25.8% (p<0.0001) at two weeks and 33.0% vs. 23.0% (p<0.0001) at four weeks. Conclusion: Most children meeting international criteria for concussion were provided this diagnosis by the ED physician. There were five variables which increased the odds of this diagnosis by at least 1.5-fold. Relative to international criteria, the more selective assignment of concussion by ED physicians was associated with a greater frequency of persistent concussion symptoms. Nevertheless, many patients with alternative diagnoses exhibited persistent concussive symptoms at all time points. Clinicians should therefore weigh the benefits and risks of strictly applying the Zurich/Berlin international criteria versus individual discretion.
Trust law has grown and developed over recent years through the continued ingenuity of practitioners and the provision of innovative new trust laws by offshore jurisdictions. The wealth managed through the medium of trust law has also changed in recent years, as increasingly it has come from the newly rich of Asia. This brings distinctive issues to the fore: the role of settlors, family members and trusted advisors in trust administration; the position of trustees in relation to instructions coming from such persons; and an increased desire for confidentiality in trust administration and the settlement of trust disputes. This collection focuses on trusts which are deliberately created to manage wealth and the concomitant issues such trusts raise in other areas of law. Essays from leading members of the judiciary, practitioners and academics explore these developments and their implications for the users of trust law and for society in general.