3,323 research outputs found
A regression based transmission/disequilibrium test for binary traits: the power of joint tests for linkage and association
BACKGROUND: In this analysis we applied a regression based transmission disequilibrium test to the binary trait presence or absence of Kofendred Personality Disorder in the Genetic Analysis Workshop 14 (GAW14) simulated dataset and determined the power and type I error rate of the method at varying map densities and sample sizes. To conduct this transmission disequilibrium test, the logit transformation was applied to a binary outcome and regressed on an indicator variable for the transmitted allele from informative matings. All 100 replicates from chromosomes 1, 3, 5, and 9 for the Aipotu and the combined Aipotu, Karangar, and Danacaa populations were used at densities of 3, 1, and 0.3 cM. Power and type I error were determined by the number of replicates significant at the 0.05 level. RESULTS: The maximum power to detect linkage and association with the Aipotu population was 93% for chromosome 3 using a 0.3-cM map. For chromosomes 1, 5, and 9 the power was less than 10% at the 3-cM scan and less than 22% for the 0.3-cM map. With the larger sample size, power increased to 38% for chromosome 1, 100% for chromosome 3, 31% for chromosome 5, and 23% for chromosome 9. Type I error was approximately 7%. CONCLUSION: The power of this method is highly dependent on the amount of information in a region. This study suggests that single-point methods are not particularly effective in narrowing a fine-mapping region, particularly when using single-nucleotide polymorphism data and when linkage disequilibrium in the region is variable
Links between traumatic brain injury and ballistic pressure waves originating in the thoracic cavity and extremities
Identifying patients at risk of traumatic brain injury (TBI) is important
because research suggests prophylactic treatments to reduce risk of long-term
sequelae. Blast pressure waves can cause TBI without penetrating wounds or
blunt force trauma. Similarly, bullet impacts distant from the brain can
produce pressure waves sufficient to cause mild to moderate TBI. The fluid
percussion model of TBI shows that pressure impulses of 15-30 psi cause mild to
moderate TBI in laboratory animals. In pigs and dogs, bullet impacts to the
thigh produce pressure waves in the brain of 18-45 psi and measurable injury to
neurons and neuroglia. Analyses of research in goats and epidemiological data
from shooting events involving humans show high correlations (r > 0.9) between
rapid incapacitation and pressure wave magnitude in the thoracic cavity. A case
study has documented epilepsy resulting from a pressure wave without the bullet
directly hitting the brain. Taken together, these results support the
hypothesis that bullet impacts distant from the brain produce pressure waves
that travel to the brain and can retain sufficient magnitude to induce brain
injury. The link to long-term sequelae could be investigated via
epidemiological studies of patients who were gunshot in the chest to determine
whether they experience elevated rates of epilepsy and other neurological
sequelae
Fossil Mobiles: Exploring the Process of Art as Science Inquiry for Elementary Students through a Grounded Theory Study
Arts integration into Science, Technology, Engineering, and Mathematics (STEM) subject areas is currently an important area of investigation. This study developed a grounded theory of how artmaking of a mobile related to fossil life of the Devonian period engendered geoscience inquiry. Data were collected from elementary students entering fourth to sixth grade (7 male, 9 female) attending a week-long summer camp at a Midwestern university. Students engaged in a daily hour-long class creating fossil mobiles and learning geoscience content through illustrated slide shows, form and function sets of materials related to Devonian fossils, fossil books, and a fossil hunter- fossil find matching game. The art fossil mobile was constructed of painted dowel rods suspended from a beaded string with four craft fossils (traced onto clear plastic and back-painted or stenciled onto canvas) attached to the ends of the rods. The grounded theory research design identified seven major repeating interactions among the triad of art, science, and students: (1) art promoting science inquiry, (2) art aspects positively influencing science learning, (3) science learning increasing interest in fossils, (4) science influencing art, (5) student-centered artwork increasing desire for more art knowledge, (6) student-centered art providing connections to science, and (7) student-centered science increasing interest in fossils. Implications for educators include integrating art activities into science lessons, thereby providing engagement and motivation for students, supporting students’ fine motor skills development, and building a community of learners. Geoscience educators should consider the positive cyclical effects of art-science-student interactions identified in this study
First-principles prediction of redox potentials in transition-metal compounds with LDA+U
First-principles calculations within the Local Density Approximation (LDA) or
Generalized Gradient Approximation (GGA), though very successful, are known to
underestimate redox potentials, such as those at which lithium intercalates in
transition metal compounds. We argue that this inaccuracy is related to the
lack of cancellation of electron self-interaction errors in LDA/GGA and can be
improved by using the DFT+ method with a self-consistent evaluation of the
parameter. We show that, using this approach, the experimental lithium
intercalation voltages of a number of transition metal compounds, including the
olivine LiMPO (M=Mn, Fe Co, Ni), layered LiMO (Co,
Ni) and spinel-like LiMO (M=Mn, Co), can be reproduced
accurately.Comment: 19 pages, 6 figures, Phys. Rev. B 70, 235121 (2004
Thyroid hormones enhance the biomechanical functionality of scaffold-free neocartilage
IntroductionThe aim of this study was to investigate the effects of thyroid hormones tri-iodothyronine (T3), thyroxine (T4), and parathyroid hormone (PTH) from the parathyroid glands, known to regulate the developing limb and growth plate, on articular cartilage tissue regeneration using a scaffold-free in vitro model.MethodsIn Phase 1, T3, T4, or PTH was applied during weeks 1 or 3 of a 4-week neocartilage culture. Phase 2 employed T3 during week 1, followed by PTH during week 2, 3, or weeks 2 to 4, to further enhance tissue properties. Resultant neotissues were evaluated biochemically, mechanically, and histologically.ResultsIn Phase 1, T3 and T4 treatment during week 1 resulted in significantly enhanced collagen production; 1.4- and 1.3-times untreated neocartilage. Compressive and tensile properties were also significantly increased, as compared to untreated and PTH groups. PTH treatment did not result in notable tissue changes. As T3 induces hypertrophy, in Phase 2, PTH (known to suppress hypertrophy) was applied sequentially after T3. Excitingly, sequential treatment with T3 and PTH reduced expression of hypertrophic marker collagen X, while yielding neocartilage with significantly enhanced functional properties. Specifically, in comparison to no hormone application, these hormones increased compressive and tensile moduli 4.0-fold and 3.1-fold, respectively.ConclusionsThis study demonstrated that T3, together with PTH, when applied in a scaffold-free model of cartilage formation, significantly enhanced functional properties. The novel use of these thyroid hormones generates mechanically robust neocartilage via the use of a scaffold-free tissue engineering model
Acute Beetroot Juice Ingestion Increases Nitric Oxide Bioavailability Without Changing Oral Microbial Composition in Healthy Young Women
Dietary nitrate supplementation can elicit beneficial health and exercise performance effects. Oral microbiota are critical for the metabolism of exogenously consumed nitrate; however, limited data are available on the influence of dietary nitrate ingestion on bacterial taxa and in women. PURPOSE: To investigate if acute dietary nitrate ingestion alters the oral microbiota in young healthy women compared to a nitrate-depleted placebo. METHODS: In a randomized double-blinded crossover design, fifteen recreationally active women (mean ± SD: age 20 ± 1 years; body mass 63 ± 10 kg; height 1.68 ± 0.1 m) participated in two conditions to ingest nitrate-rich beetroot juice (BR; 12 mmol of nitrate) and nitrate-depleted beetroot juice (PL, negligible nitrate), 2.5 hours prior to a resting blood draw and buccal swab sample. Plasma [nitrate] and [nitrite] were analyzed using gas phase chemiluminescence. Buccal swab samples were used for DNA extraction and isolation. DNA was amplified using polymerase chain reaction targeting the V3 - V4 region of the 16S rRNA gene. Following index PCR, amplicons were pooled and sequenced using the iSeq Illumina NGS sequencer. Reads were clustered into amplicon sequence variants and analyzed for alpha and beta diversity and relative abundance. RESULTS: BR increased plasma [nitrate] (PL: 52 ± 14 µM vs. BR: 629 ± 132 µM, P \u3c 0.001) and plasma [nitrite] (PL: 276 ± 286 nM vs. BR: 703 ± 391 nM, P \u3c 0.001). One sample had insufficient DNA and thus, a subset of samples was analyzed for oral microbial composition (n = 14). Alpha (i.e., species richness or evenness) and beta diversity was not different between PL and BR (P \u3e 0.05). The relative abundance of the phylum and genus were not influenced by BR (P \u3e 0.05). CONCLUSION: Acute nitrate ingestion did not improve or worsen the composition of global or lower taxonomic levels of bacteria in young recreationally active women. These data indicate that acute nitrate ingestion is an intervention to rapidly increase nitric oxide bioavailability in young recreationally active women, which is an effect that did not require changes to the oral microbial community. Further research is required to understand the impact of dosing regimen and population on oral bacterial taxa and the efficacy of nitrate on nitrate-induced effects
Angiotensin II and angiotensin-(1-7) decrease sFlt1 release in normal but not preeclamptic chorionic villi: an in vitro study
<p>Abstract</p> <p>Background</p> <p>During preeclampsia, placental angiogenesis is impaired. Factors released from the placenta including vascular endothelial growth factor (VEGF), placental growth factor (PLGF), soluble VEGF receptor 1 (sFlt1), and soluble endoglin (sEng) are regulatory molecules of placental development and function. While the renin angiotensin system has been shown to regulate angiogenic factors in other research fields, these mechanisms have not been extensively studied during pregnancy.</p> <p>Methods</p> <p>We evaluated the effects of angiotensin II (Ang II) and angiotensin-(1-7) [Ang-(1-7)] on the release of VEGF, PLGF, sFlt1, and sEng from placental chorionic villi (CV). CV were collected from nulliparous third-trimester normotensive and preeclamptic subjects. CV were incubated for 0, 2, 4, and 16 hours with or without Ang II (1 nM and 1 microM) or Ang-(1-7) (1 nM and 1 microM). The release of VEGF, PLGF, sFlt1, sEng, lactate dehydrogenase (LDH), and human placenta lactogen (HPL) was measured by ELISA.</p> <p>Results</p> <p>The release of sFlt1, PLGF, sEng from normal and preeclamptic CV increased over time. Release of sFlt1 and sEng was significantly higher from preeclamptic CV. VEGF was below the detectable level of the assay in normal and preeclamptic CV. After 2 hours, sFlt1 release from normal CV was significantly inhibited with Ang II (1 nM and 1 microM) and Ang-(1-7) (1 nM and 1 microM). There was a time-dependent increase in HPL indicating that the CV were functioning normally.</p> <p>Conclusions</p> <p>Our study demonstrates a critical inhibitory role of angiotensin peptides on sFlt1 in normal pregnancy. Loss of this regulation in preeclampsia may allow sFlt1 to increase resulting in anti-angiogenesis and end organ damage in the mother.</p
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FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs.
Chondrodystrophy in dogs is defined by dysplastic, shortened long bones and premature degeneration and calcification of intervertebral discs. Independent genome-wide association analyses for skeletal dysplasia (short limbs) within a single breed (PBonferroni = 0.01) and intervertebral disc disease (IVDD) across breeds (PBonferroni = 4.0 × 10-10) both identified a significant association to the same region on CFA12. Whole genome sequencing identified a highly expressed FGF4 retrogene within this shared region. The FGF4 retrogene segregated with limb length and had an odds ratio of 51.23 (95% CI = 46.69, 56.20) for IVDD. Long bone length in dogs is a unique example of multiple disease-causing retrocopies of the same parental gene in a mammalian species. FGF signaling abnormalities have been associated with skeletal dysplasia in humans, and our findings present opportunities for both selective elimination of a medically and financially devastating disease in dogs and further understanding of the ever-growing complexity of retrogene biology
Streamlining Sporozoite Isolation From Mosquitoes by Leveraging the Dynamics of Migration to the Salivary Glands
Background: Sporozoites isolated from the salivary glands of Plasmodium-infected mosquitoes are a prerequisite for several basic and pre-clinical applications. Although salivary glands are pooled to maximize sporozoite recovery, insufficient yields pose logistical and analytical hurdles; thus, predicting yields prior to isolation would be valuable. Preceding oocyst densities in the midgut is an obvious candidate. However, it is unclear whether current understanding of its relationship with sporozoite densities can be used to maximize yields, or whether it can capture the potential density-dependence in rates of sporozoite invasion of the salivary glands.
Methods: This study presents a retrospective analysis of Anopheles stephensi mosquitoes infected with two strains of the rodent-specific Plasmodium berghei. Mean oocyst densities were estimated in the midguts earlier in the infection (11-15 days post-blood meal), with sporozoites pooled from the salivary glands later in the infection (17-29 days). Generalized linear mixed effects models were used to determine if (1) mean oocyst densities can predict sporozoite yields from pooled salivary glands, (2) whether these densities can capture differences in rates of sporozoite invasion of salivary glands, and (3), if the interaction between oocyst densities and time could be leveraged to boost overall yields.
Results: The non-linear effect of mean oocyst densities confirmed the role of density-dependent constraints in limiting yields beyond certain oocyst densities. Irrespective of oocyst densities however, the continued invasion of salivary glands by the sporozoites boosted recoveries over time (17-29 days post-blood meal) for either parasite strain.
Conclusions: Sporozoite invasion of the salivary glands over time can be leveraged to maximize yields for P. berghei. In general, however, invasion of the salivary glands over time is a critical fitness determinant for all Plasmodium species (extrinsic incubation period, EIP). Thus, delaying sporozoite collection could, in principle, substantially reduce dissection effort for any parasite within the genus, with the results also alluding to the potential for changes in sporozoites densities over time to modify infectivity for the next host
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