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61.
Michael R. La Frano Suzan L. Carmichael Chen Ma Macy Hardley Tong Shen Ron Wong Lorenzo Rosales Kamil Borkowski Theresa L. Pedersen Gary M. Shaw David K. Stevenson Oliver Fiehn John W. Newman 《Metabolomics : Official journal of the Metabolomic Society》2018,14(11):151
Background
Population-based biorepositories are important resources, but sample handling can affect data quality.Objective
Identify metabolites of value for clinical investigations despite extended postcollection freezing delays, using protocols representing a California mid-term pregnancy biobank.Methods
Blood collected from non-pregnant healthy female volunteers (n?=?20) underwent three handling protocols after 30 min clotting at room temperature: (1) ideal—samples frozen (??80 °C) within 2 h of collection; (2) delayed freezing—samples held at room temperature for 3 days, then 4 °C for 9 days, the median times for biobank samples, and then frozen; (3) delayed freezing with freeze–thaw—the delayed freezing protocol with a freeze–thaw cycle simulating retrieved sample sub-aliquoting. Mass spectrometry-based untargeted metabolomic analyses of primary metabolism and complex lipids and targeted profiling of oxylipins, endocannabinoids, ceramides/sphingoid-bases, and bile acids were performed. Metabolite concentrations and intraclass correlation coefficients (ICC) were compared, with the ideal protocol as the reference.Results
Sixty-two percent of 428 identified compounds had good to excellent ICCs, a metric of concordance between measurements of samples handled with the different protocols. Sphingomyelins, phosphatidylcholines, cholesteryl esters, triacylglycerols, bile acids and fatty acid diols were the least affected by non-ideal handling, while sugars, organic acids, amino acids, monoacylglycerols, lysophospholipids, N-acylethanolamides, polyunsaturated fatty acids, and numerous oxylipins were altered by delayed freezing. Freeze–thaw effects were assay-specific with lipids being most stable.Conclusions
Despite extended post-collection freezing delays characteristic of some biobanks of opportunistically collected clinical samples, numerous metabolomic compounds had both stable levels and good concordance.62.
Given the rarity of hybridization in seabirds, which presumably relates to their very high philopatry, the degree of breeding‐site vagrancy should correspond with the incidence of mixed‐species pairing, although not necessarily with the production of hybrids if there are behavioural or genetic barriers to successful reproduction. Using molecular methods, we verified that two of the three chicks hatched by a vagrant male White‐capped Albatross Thalassarche steadi paired with a female Black‐browed Albatross Thalassarche melanophris at South Georgia were genuine hybrids (these chicks died before fledging, but a third chick – the result of an extra‐pair copulation – fledged successfully). In a wider review, we could find only five known or suspected mixed‐species pairs, and three different hybrids in albatrosses, mostly between closely related species. This appears to reflect behavioural barriers to hybridization in sympatric species and the low incidence of breeding‐site vagrancy (which mainly involves single individuals that invariably associate with the most phenotypically similar local taxon). Breeding‐site vagrancy is most frequent in the ‘shy‐albatross’ complex, which could explain why genetic divergence occurred more recently in this group than in other Thalassarche, and hence exploratory behaviour appears to be more important than numerical abundance or breeding distribution in driving colonization as well as hybridization processes in albatrosses. 相似文献
63.
Theresa A. Grebe William K. Seltzer Jean DeMarchi Dinithi K. Silva W. W. Doane David Gozal S. F. Richter C. Michael Bowman R. A. Norman Susan N. Rhodes Lucy S. Hernried Shirley Murphy Ivan R. Harwood Frank J. Accurso Karen D. Jain 《American journal of human genetics》1994,54(3):443-446
We have performed molecular genetic analyses of Hispanic individuals with cystic fibrosis (CF) in the southwestern United States. Of 129 CF chromosomes analyzed, only 46% (59/129) carry ΔF508. The G542X mutation was found on 5% (7/129) of CF chromosomes. The 3849+10kbC→T mutation, detected primarily in Ashkenazi Jews, was present on 2% (3/129). R1162X and R334W, mutations identified in Spain and Italy, each occurred on 1.6% (2/129) of CF chromosomes. W1282X and R553X were each detected once. G551D and N1303K were not found. Overall, screening for 22 or more mutations resulted in detection of only 58% of CF transmembrane conductance regulator gene mutations among Hispanic individuals. Analysis of KM19/XV2c haplotypes revealed an unusual distribution. Although the majority of ΔF508 mutations are on chromosomes of B haplotypes, the other CF mutations are on A and C haplotypes at higher-than-expected frequencies. These genetic analyses demonstrate significant differences between Hispanic individuals with CF and those of the general North American population. Assessment of carrier/affected risk in Hispanic CF individuals cannot, therefore, be based on the mutation frequencies found through studies of the general population but must be adjusted to better reflect the genetic makeup of this ethnic group. Further studies are necessary to identify the causative mutation(s) in this population and to better delineate genotype/phenotype correlations. These will enable counselors to provide more accurate genetic counseling. 相似文献
64.
Locus Heterogeneity for Waardenburg Syndrome is Predictive of Clinical Subtypes 总被引:1,自引:4,他引:1 下载免费PDF全文
Lindsay A. Farrer Kathleen S. Arnos James H. Asher Clinton T. Baldwin Scott R. Diehl Thomas B. Friedman Jacquie Greenberg Kenneth M. Grundfast Christopher Hoth Anil K. Lalwani Barbara Landa Kate Leverton Aubrey Milunsky Robert Morell Walter E. Nance Valerie Newton Rajkumar Ramesar Valluri S. Rao Jennifer E. Reynolds Theresa B. San Agustin Edward R. Wilcox Ingrid Winship Andrew P. Read 《American journal of human genetics》1994,55(4):728-737
Waardenburg syndrome (WS) is a dominantly inherited and clinically variable syndrome of deafness, pigmentary changes, and distinctive facial features. Clinically, WS type I (WS1) is differentiated from WS type II (WS2) by the high frequency of dystopia canthorum in the family. In some families, WS is caused by mutations in the PAX3 gene on chromosome 2q. We have typed microsatellite markers within and flanking PAX3 in 41 WS1 kindreds and 26 WS2 kindreds in order to estimate the proportion of families with probable mutations in PAX3 and to study the relationship between phenotypic and genotypic heterogeneity. Evaluation of heterogeneity in location scores obtained by multilocus analysis indicated that WS is linked to PAX3 in 60% of all WS families and in 100% of WS1 families. None of the WS2 families were linked. In those families in which equivocal lod scores (between −2 and +1) were found, PAX3 mutations have been identified in 5 of the 15 WS1 families but in none of the 4 WS2 families. Although preliminary studies do not suggest any association between the phenotype and the molecular pathology in 20 families with known PAX3 mutations and in four patients with chromosomal abnormalities in the vicinity of PAX3, the presence of dystopia in multiple family members is a reliable indicator for identifying families likely to have a defect in PAX3. 相似文献
65.
On 16 June 1979, a herd of 41 sperm whales stranded near the mouth of the Siuslaw River in Florence, Oregon. The stomach contents from 32 whales were collected, identified to the lowest taxonomic level possible, enumerated, and measured. A total of 20,247 cephalopod lower beaks that represented 24 species from 14 different families were recovered. The most numerous species were Histioteuthis hoylei (25.9%), Taonius borealis (12.9%), Galiteuthis phyllura (11.2%), Gonatopsis/Berryteuthis type (10.9%), and Moroteuthis robusta (10.7%). Reconstructed estimates of mass indicated that M. robusta contributed almost 50% of the total mass of cephalopods consumed, followed by H. hoylei (19.3%), and T. borealis (7.0%). The most important species in the diet of stranded whales were M. robusta, H. hoylei, T. borealis, G. phyllura, Octopoteuthis deletron, and Gonatopsis/Berryteuthis type. There were significant differences in the diet of males and females, but no differences between sperm whales of different age groups. Overall, sperm whales primarily consumed small cephalopods that were likely eaten south of 45ºN in or near the California Current System. This study provides new estimates of the food habits of sperm whales in the northeast Pacific from one of the largest strandings of this species. 相似文献
66.
Michael Meyer Maya Ben‐Yehuda Greenwald Theresa Rauschendorfer Catharina Snger Marko Jukic Haruka Iizuka Fumimasa Kubo Lin Chen David M. Ornitz Sabine Werner 《Journal of cellular and molecular medicine》2020,24(2):1774-1785
Fibroblast growth factors (FGFs) are key regulators of tissue development, homeostasis and repair, and abnormal FGF signalling is associated with various human diseases. In human and murine epidermis, FGF receptor 3 (FGFR3) activation causes benign skin tumours, but the consequences of FGFR3 deficiency in this tissue have not been determined. Here, we show that FGFR3 in keratinocytes is dispensable for mouse skin development, homeostasis and wound repair. However, the defect in the epidermal barrier and the resulting inflammatory skin disease that develops in mice lacking FGFR1 and FGFR2 in keratinocytes were further aggravated upon additional loss of FGFR3. This caused fibroblast activation and fibrosis in the FGFR1/FGFR2 double‐knockout mice and even more in mice lacking all three FGFRs, revealing functional redundancy of FGFR3 with FGFR1 and FGFR2 for maintaining the epidermal barrier. Taken together, our study demonstrates that FGFR1, FGFR2 and FGFR3 act together to maintain epidermal integrity and cutaneous homeostasis, with FGFR2 being the dominant receptor. 相似文献
67.
Frances E. Tiffin-Richards Ana S. Costa Bernhard Holschbach Rolf D. Frank Athina Vassiliadou Thilo Krüger Karl Kuckuck Theresa Gross Frank Eitner Jürgen Floege J?rg B. Schulz Kathrin Reetz 《PloS one》2014,9(10)
Background
Chronic kidney disease (CKD) patients undergoing hemodialysis (HD) therapy have an increased risk of developing cognitive impairment and dementia, which are known relevant factors in disease prognosis and therapeutic success, but still lack adequate screening in clinical routine. We evaluated the Montreal Cognitive Assessment (MoCA) for suitability in assessing cognitive performance in HD patients in comparison to the commonly used Mini-Mental State Examination (MMSE) and a detailed neuropsychological test battery, used as gold standard.Methods
43 HD patients and 42 healthy controls with an average age of 58 years, were assessed with the MoCA, the MMSE and a detailed neuropsychological test battery, covering the domains of memory, attention, language, visuospatial and executive functions. Composite scores were created for comparison of cognitive domains and test results were analyzed using Spearman''s correlation and linear regression. Cognitive dysfunction was defined using z-score values and predictive values were calculated. Sensitivity and specificity of the MoCA were determined using receiver operating characteristic (ROC) analysis.Results
HD patients performed worse in all cognitive domains, especially in memory recall and executive functions. The MoCA correlated well with the detailed test battery and identified patients with cognitive impairment with a sensitivity of 76.7% and specificity of 78.6% for a cut-off value of ≤24 out of 30 points. In the detailed assessment executive functions accounted significantly for performance in the MoCA. The MMSE only discriminated weakly between groups.Conclusions
The MoCA represents a suitable cognitive screening tool for hemodialysis patients, demonstrating good sensitivity and specificity levels, and covering executive functions, which appear to play an important role in cognitive performance of HD patients. 相似文献68.
Host behaviour drives parasite genetics at multiple geographic scales: population genetics of the chewing louse,Thomomydoecus minor 下载免费PDF全文
Sheree E. Harper Theresa A. Spradling James W. Demastes Courtney S. Calhoun 《Molecular ecology》2015,24(16):4129-4144
Pocket gophers and their symbiotic chewing lice form a host–parasite assemblage known for a high degree of cophylogeny, thought to be driven by life history parameters of both host and parasite that make host switching difficult. However, little work to date has focused on determining whether these life histories actually impact louse populations at the very fine scale of louse infrapopulations (individuals on a single host) at the same or at nearby host localities. We used microsatellite and mtDNA sequence data to make comparisons of chewing‐louse (Thomomydoecus minor) population subdivision over time and over geographic space where there are different potential amounts of host interaction surrounding a zone of contact between two hybridizing pocket‐gopher subspecies. We found that chewing lice had high levels of population isolation consistent with a paucity of horizontal transmission even at the very fine geographic scale of a single alfalfa field. We also found marked genetic discontinuity in louse populations corresponding with host subspecies and little, if any, admixture in the louse genetic groups even though the lice are closely related. The correlation of louse infrapopulation differentiation with host interaction at multiple scales, including across a discontinuity in pocket‐gopher habitat, suggests that host behaviour is the primary driver of parasite genetics. This observation makes sense in light of the life histories of both chewing lice and pocket gophers and provides a powerful explanation for the well‐documented pattern of parallel cladogenesis in pocket gophers and chewing lice. 相似文献
69.
Massimo Maddaloni Irina Kochetkova SangMu Jun Gayle Callis Theresa Thornburg David W. Pascual 《PloS one》2015,10(1)
Autoimmune diseases arise from the loss of tolerance to self, and because the etiologies of such diseases are largely unknown, symptomatic treatments rely on anti-inflammatory and analgesic agents. Tolerogenic treatments that can reverse disease are preferred, but again, often thwarted by not knowing the responsible auto-antigens (auto-Ags). Hence, a viable alternative to stimulating regulatory T cells (Tregs) is to induce bystander tolerance. Colonization factor antigen I (CFA/I) has been shown to evoke bystander immunity and to hasten Ag-specific Treg development independent of auto-Ag. To translate in treating human autoimmune diseases, the food-based Lactococcus was engineered to express CFA/I fimbriae, and Lactococcus-CFA/I fermented milk fed to arthritic mice proved highly efficacious. Protection occurred via CD39+ Tregs producing TGF-β and IL-10 to potently suppress TNF-α production and neutrophil influx into the joints. Thus, these data demonstrate the feasibility of oral nutraceuticals for treating arthritis, and potency of protection against arthritis was improved relative to that obtained with Salmonella-CFA/I. 相似文献
70.