Genetic merit for fertility traits in Holstein cows: VI. Oocyte developmental competence and embryo development

peer-reviewedThe hypothesis of this study was that cows with good genetic merit for fertility traits (Fert+) would produce oocytes and embryos of greater quality than cows with poor genetic merit for fertility traits (Fert−) and that mRNA expression of candidate genes would reflect the observed differences in quality. The aim of the study, therefore, was to determine the effect of genetic merit for fertility traits on morphological classification and mRNA abundance of key genes in immature oocytes and cumulus cells following ovum pick-up and in embryos following superovulation, artificial insemination (AI), and uterine flushing. In experiment 1, 17 Fert+ and 11 Fert− cows, ranging from 54 to 84 d in milk, were submitted to ovum pick-up on 4 occasions during a 2-wk period. Recovered cumulus–oocyte complexes (COC) were morphologically graded. Oocytes and cumulus cells were separated, and mRNA abundance of genes associated with oocyte developmental competence was measured. There was no effect of genotype on the distribution of COC grades or on the mRNA abundance of the candidate genes in grade 1 COC. In experiment 2, 20 Fert+ and 19 Fert− cows, ranging from 71 to 189 d in milk, were submitted to superovulation and AI. The uteri of cows that responded to the superovulation protocol (17 Fert+ and 16 Fert− cows) were nonsurgically flushed 7 d postovulation. Recovered embryos were morphologically graded, and mRNA abundance of genes associated with embryo development was measured in grade 1 blastocysts. The response to the superovulation protocol was assessed by counting the number of codominant follicles on the day of AI, which was similar for both genotypes (22.0 ± 9.7 and 19.8 ± 8.2 for Fert+ and Fert− cows, respectively). There was no effect of genotype on the proportion of transferable embryos recovered or on the mRNA abundance of the candidate genes tested in the grade 1 blastocysts. Of the total embryos classified as blastocysts, however, the Fert+ cows tended to have a greater proportion of grade 1 blastocysts compared with Fert− cows (90% vs. 64%, respectively). In conclusion, genetic merit for fertility traits had a no effect on mRNA abundance of the candidate genes that were examined in immature oocytes and cumulus cells and in embryos recovered after superovulation. The observed differences in morphological blastocyst quality following superovulation would suggest that the superior reproductive performance of Fert+ cows could arise during the later stages of embryo development from d 7 until maternal recognition of pregnancy

Detection of the transforming AKT1 mutation E17K in non-small cell lung cancer by high resolution melting

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Computed Analysis of Three-Dimensional Cone-Beam Computed Tomography Angiography for Determination of Tumor-Feeding Vessels During Chemoembolization of Liver Tumor: A Pilot Study

The purpose of this study was to evaluate computed analysis of three-dimensional (3D) cone-beam computed tomography angiography (CTA) of the liver for determination of subsegmental tumor-feeding vessels (FVs). Eighteen consecutive patients underwent transarterial chemoembolization (TACE) from January to October 2008 for 25 liver tumors (15 hepatocellular carcinomas [HCCs] and 10 neuroendocrine metastases). Anteroposterior projection angiogram (two-dimensional [2D]) and 3D cone-beam CTA images were acquired by injection of the common hepatic artery. Retrospectively, FVs were independently identified by three radiology technologists using a software package (S) that automatically determines FVs by analysis of 3D images. Subsequently, three interventional radiologists (IRs) independently identified FVs by reviewing the 2D images followed by examination of the 3D images. Finally, the “ground truth” for the number and location of FVs was obtained by consensus among the IRs, who were allowed to use any imaging―including 2D, 3D, and all oblique or selective angiograms―for such determination. Sensitivities, durations, and degrees of agreement for review of 2D, 3D, and S results were evaluated. Sensitivity of 3D (73%) was higher than 2D (64%) images for identification of FVs (P = 0.036). The sensitivity of S (93%) was higher than 2D (P = 0.02) and 3D (P = 0.005) imaging. The duration for review of 3D imaging was longer than that for 2D imaging (187 vs. 94 s, P = 0.0001) or for S (135 s, P = 0.0001). The degree of agreement between the IRs using 2D and 3D imaging were 54% and 62%, respectively, whereas it was 82% between the three radiology technologists using S. These preliminary data show that computed determination of FVs is both accurate and sensitive

Shear Wave Splitting Analyses in Tian Shan: Geodynamic Implications of Complex Seismic Anisotropy

The Tian Shan is a tectonically complex intracontinental orogenic belt situated between the Tarim Basin and the Kazakh Shield. The vast majority of the previous shear wave splitting (SWS) measurements were presented as station averages, which are only valid when the anisotropy structure can be approximated by a single layer of anisotropy with a horizontal axis of symmetry, i.e., a model of simple anisotropy. A variety of anisotropy-forming hypotheses have been proposed based on the station-averaged measurements. In this study, we measure the splitting parameters at 25 stations that recorded high-quality data from a wide back azimuthal range for the purpose of identifying and characterizing complex anisotropy. Among the 25 stations, 15 of them show systematic azimuthal variations in the observed splitting parameters with a 90° periodicity that is consistent with a model of two-layered anisotropy. The fast orientations of the upper layer range from 50° to 90° measured clockwise from the north, which are subparallel to the strike of the orogenic belt, and the splitting times are between 0.9 and 1.9 s. The corresponding values for the lower layer are -45° to -85° and 1.2-2.2 s, respectively. The remaining 10 stations demonstrate azimuthally invariant splitting parameters with strike-parallel fast orientations, and can be represented by a single layer of anisotropy with a horizontal axis of symmetry. We propose that the strike-parallel anisotropy is caused by lithospheric shortening, and anisotropy in the lower layer is associated with WNW-ward flow of asthenospheric material sandwiched between the subducting Tarim lithosphere and the thick Kazakh lithospheric root

Outer-Sphere Contributions to the Electronic Structure of Type Zero Copper Proteins

Bioinorganic canon states that active-site thiolate coordination promotes rapid electron transfer (ET) to and from type 1 copper proteins. In recent work, we have found that copper ET sites in proteins also can be constructed without thiolate ligation (called “type zero” sites). Here we report multifrequency electron paramagnetic resonance (EPR), magnetic circular dichroism (MCD), and nuclear magnetic resonance (NMR) spectroscopic data together with density functional theory (DFT) and spectroscopy-oriented configuration interaction (SORCI) calculations for type zero Pseudomonas aeruginosa azurin variants. Wild-type (type 1) and type zero copper centers experience virtually identical ligand fields. Moreover, O-donor covalency is enhanced in type zero centers relative that in the C112D (type 2) protein. At the same time, N-donor covalency is reduced in a similar fashion to type 1 centers. QM/MM and SORCI calculations show that the electronic structures of type zero and type 2 are intimately linked to the orientation and coordination mode of the carboxylate ligand, which in turn is influenced by outer-sphere hydrogen bonding

Multidomain interventions: state-of-the-art and future directions for protocols to implement precision dementia risk reduction. A user manual for Brain Health Services-part 4 of 6.

Although prevention of dementia and late-life cognitive decline is a major public health priority, there are currently no generally established prevention strategies or operational models for implementing such strategies into practice. This article is a narrative review of available evidence from multidomain dementia prevention trials targeting several risk factors and disease mechanisms simultaneously, in individuals without dementia at baseline. Based on the findings, we formulate recommendations for implementing precision risk reduction strategies into new services called Brain Health Services. A literature search was conducted using medical databases (MEDLINE via PubMed and SCOPUS) to select relevant studies: non-pharmacological multidomain interventions (i.e., combining two or more intervention domains), target population including individuals without dementia, and primary outcomes including cognitive/functional performance changes and/or incident cognitive impairment or dementia. Further literature searches covered the following topics: sub-group analyses assessing potential modifiers for the intervention effect on cognition in the multidomain prevention trials, dementia risk scores used as surrogate outcomes in multidomain prevention trials, dementia risk scores in relation to brain pathology markers, and cardiovascular risk scores in relation to dementia. Multidomain intervention studies conducted so far appear to have mixed results and substantial variability in target populations, format and intensity of interventions, choice of control conditions, and outcome measures. Most trials were conducted in high-income countries. The differences in design between the larger, longer-term trials that met vs. did not meet their primary outcomes suggest that multidomain intervention effectiveness may be dependent on a precision prevention approach, i.e., successfully identifying the at-risk groups who are most likely to benefit. One such successful trial has already developed an operational model for implementing the intervention into practice. Evidence on the efficacy of risk reduction interventions is promising, but not yet conclusive. More long-term multidomain randomized controlled trials are needed to fill the current evidence gaps, especially concerning low- and middle-income countries and integration of dementia prevention with existing cerebrovascular prevention programs. A precision risk reduction approach may be most effective for dementia prevention. Such an approach could be implemented in Brain Health Services

Duration of Rheumatoid Arthritis and the Risk of Developing Interstitial Lung Disease

Age of ILD onset is similar in patients with RA-UIP and RA-NSIP but duration of RA before ILD onset differs

Open-access mega-journals: A bibliometric profile

In this paper we present the first comprehensive bibliometric analysis of eleven open-access mega-journals (OAMJs). OAMJs are a relatively recent phenomenon, and have been characterised as having four key characteristics: large size; broad disciplinary scope; a GoldOA business model; and a peer-review policy that seeks to determine only the scientific soundness of the research rather than evaluate the novelty or significance of the work. Our investigation focuses on four key modes of analysis: journal outputs (the number of articles published and changes in output over time); OAMJ author characteristics (nationalities and institutional affiliations); subject areas (the disciplinary scope of OAMJs, and variations in sub-disciplinary output); and citation profiles (the citation distributions of each OAMJ, and the impact of citing journals). We found that while the total output of the eleven megajournals grew by 14.9% between 2014 and 2015, this growth is largely attributable to the increased output of Scientific Reports and Medicine. We also found substantial variation in the geographical distribution of authors. Several journals have a relatively high proportion of Chinese authors, and we suggest this may be linked to these journals’ high Journal Impact Factors (JIFs). The mega-journals were also found to vary in subject scope, with several journals publishing disproportionately high numbers of articles in certain sub-disciplines. Our citation analsysis offers support for Björk & Catani’s suggestion that OAMJs’s citation distributions can be similar to those of traditional journals, while noting considerable variation in citation rates across the eleven titles. We conclude that while the OAMJ term is useful as a means of grouping journals which share a set of key characteristics, there is no such thing as a “typical” mega-journal, and we suggest several areas for additional research that might help us better understand the current and future role of OAMJs in scholarly communication

Human Genome-Wide RNAi Screen Identifies an Essential Role for Inositol Pyrophosphates in Type-I Interferon Response

The pattern recognition receptor RIG-I is critical for Type-I interferon production. However, the global regulation of RIG-I signaling is only partially understood. Using a human genome-wide RNAi-screen, we identified 226 novel regulatory proteins of RIG-I mediated interferon-β production. Furthermore, the screen identified a metabolic pathway that synthesizes the inositol pyrophosphate 1-IP7 as a previously unrecognized positive regulator of interferon production. Detailed genetic and biochemical experiments demonstrated that the kinase activities of IPPK, PPIP5K1 and PPIP5K2 (which convert IP5 to1-IP7) were critical for both interferon induction, and the control of cellular infection by Sendai and influenza A viruses. Conversely, ectopically expressed inositol pyrophosphate-hydrolases DIPPs attenuated interferon transcription. Mechanistic experiments in intact cells revealed that the expression of IPPK, PPIP5K1 and PPIP5K2 was needed for the phosphorylation and activation of IRF3, a transcription factor for interferon. The addition of purified individual inositol pyrophosphates to a cell free reconstituted RIG-I signaling assay further identified 1-IP7 as an essential component required for IRF3 activation. The inositol pyrophosphate may act by β-phosphoryl transfer, since its action was not recapitulated by a synthetic phosphonoacetate analogue of 1-IP7. This study thus identified several novel regulators of RIG-I, and a new role for inositol pyrophosphates in augmenting innate immune responses to viral infection that may have therapeutic applications