MicroRNA in ovarian function Maalouf, S. W; Liu, W. S; Pate, J. L
Cell and Tissue Research,
01/2016, Volume:
363, Issue:
1
Journal Article, Book Review
Peer reviewed
The mammalian ovary is a dynamic organ. The coordination of follicle recruitment, selection, and ovulation and the timely development and regression of the corpus luteum are essential for a ...functional ovary and fertility. Deregulation of any of these processes results in ovarian dysfunction and potential infertility. MicroRNA (miRNA) are short noncoding RNA that regulate developmental processes and time-sensitive functions. The expression of miRNA in the ovary varies with cell type, function, and stage of the estrous cycle. miRNA are involved in the formation of primordial follicles, follicular recruitment and selection, follicular atresia, oocyte-cumulus cell interaction, granulosal cell function, and luteinization. miRNA are differentially expressed in luteal cells at the various stages of the estrous cycle and during maternal recognition of pregnancy, suggesting a role in luteal development, maintenance, and regression. An understanding of the patterns of expression and functions of miRNA in the ovary will lead to novel therapeutics to treat ovarian dysfunction and improve fertility and, potentially, to the development of better contraceptives.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The first structurally characterized copper cluster with a Cu13 centered cuboctahedral arrangement, a model of the bulk copper fcc structure, was observed in Cu13(S2CNnBu2)6(C≡CR)4(PF6) (R=C(O)OMe, ...C6H4F) nanoclusters. Four of the eight triangular faces of the cuboctahedron are capped by acetylide groups in μ3 fashion, and each of the six square faces is bridged by a dithiolate ligand in μ2,μ2 fashion, which leads to a truncated tetrahedron of twelve sulfur atoms. DFT calculations are fully consistent with the description of these Cu13 clusters as two‐electron superatoms, that is, a Cu1311+ core passivated by ten monoanionic ligands, with an a1 HOMO containing two 1S jellium electrons.
Just like in the metal: Cu13 clusters with a centered cuboctahedral unit, a model of the bulk Cu metal fcc structure, have been synthesized. The Cu1311+ core can be described as a two‐electron superatom; four of the eight triangular faces are capped by acetylide groups, and each of the six square faces is bridged by a dithiolate ligand to yield ideal tetrahedral symmetry.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The measurement of the energy spectrum of cosmic ray helium nuclei from 70 GeV to 80 TeV using 4.5 years of data recorded by the Dark Matter Particle Explorer (DAMPE) is reported in this work. A ...hardening of the spectrum is observed at an energy of about 1.3 TeV, similar to previous observations. In addition, a spectral softening at about 34 TeV is revealed for the first time with large statistics and well controlled systematic uncertainties, with an overall significance of 4.3σ. The DAMPE spectral measurements of both cosmic protons and helium nuclei suggest a particle charge dependent softening energy, although with current uncertainties a dependence on the number of nucleons cannot be ruled out.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
The beliefs we hold about stress play an important role in coping with stressors. Various theoretical frameworks of stress point to the efficacy of reframing stress-related information through brief ...reappraisal interventions in order to promote adaptive coping.
The goal of the current meta-analysis and systematic review is to substantiate the efficacy of reappraisal interventions on stress responsivity compared to control conditions. Differences in experimental methodologies (e.g., type of stressor used, timing of reappraisal intervention, and content of intervention instructions) will be examined to further delineate their effects on intervention outcomes.
The literature searches were conducted on May 16, 2018 using PsycINFO, ProQuest Dissertations and Theses, and PILOTS databases with no date restriction. The search terms included stress, reframing, reappraisal, mindset and reconceptualising. A total of 14 articles with 36 independent samples were included in the meta-analysis, while 22 articles with 46 independent samples were included in the systematic review. Random-effects model was used to test the null hypothesis using two-tailed significance testing. Fisher's Z value was reported for each corresponding test. Heterogeneity tests are reported via Cochran's Q-statistics.
Findings from both the meta-analysis and systematic review revealed that overall, reappraisal interventions are effective in attenuating subjective responsivity to stress. Standard differences in means across groups are 0.429 (SE = 0.185, 95% CI = 0.067 to 0.791; z = 2.320, p = .020). However, reappraisal intervention groups did not outperform control groups on measures of physiological stress, with standard differences of -0.084 (SE = 0.135, 95% CI = -0.349 to 0.180; z = -0.627, p = .531). Moderator analysis revealed heterogeneous effects suggesting large variability in findings.
On one hand, findings may suggest a promising avenue for the effective management of self-reported stress and optimization of stress responses. However, more research is needed to better elucidate the effects, if any, of reappraisal interventions on stress physiology. Implications for the use of reappraisal interventions on stress optimization are discussed in the context of theoretical frameworks and considerations for future studies.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Highlights • Liraglutide and lixisenatide protect mice from MPTP toxicity, a model of Parkinson’s disease. • Both drugs are currently on the market to treat type 2 diabetes. • Neuroprotective effects ...in PD are shown for the first time here. • Clinical trials are in preparation in Parkinson’s patients, testing these drugs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary Our understanding of dysfunction of the gastrointestinal system in patients with Parkinson's disease has increased substantially in the past decade. The entire gastrointestinal tract is ...affected in these patients, causing complications that range from oral issues, including drooling and swallowing problems, to delays in gastric emptying and constipation. Additionally, small intestinal bacterial overgrowth and Helicobacter pylori infection affect motor fluctuations by interfering with the absorption of antiparkinsonian drugs. The multifaceted role of the gastrointestinal system in Parkinson's disease necessitates a specific and detailed assessment and treatment plan. The presence of pervasive α-synuclein deposition in the gastrointestinal tract strongly implicates this system in the pathogenesis of Parkinson's disease. Future studies elucidating the role of the gastrointestinal tract in the pathological progression of Parkinson's disease might hold potential for early disease detection and development of neuroprotective approaches.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In neuroblastoma, the interplay between immune cells of the tumor microenvironment and cancer cells contributes to immune escape mechanisms and drug resistance. In this study, we show that natural ...killer (NK) cell-derived exosomes carrying the tumor suppressor microRNA (miR)-186 exhibit cytotoxicity against MYCN-amplified neuroblastoma cell lines. The cytotoxic potential of these exosomes was partly dependent upon expression of miR-186. miR-186 was downregulated in high-risk neuroblastoma patients, and its low expression represented a poor prognostic factor that directly correlated with NK activation markers (i.e., NKG2D and DNAM-1). Expression of MYCN, AURKA, TGFBR1, and TGFBR2 was directly inhibited by miR-186. Targeted delivery of miR-186 to MYCN-amplified neuroblastoma or NK cells resulted in inhibition of neuroblastoma tumorigenic potential and prevented the TGFβ1-dependent inhibition of NK cells. Altogether, these data support the investigation of a miR-186-containing nanoparticle formulation to prevent tumor growth and TGFβ1-dependent immune escape in high-risk neuroblastoma patients as well as the inclusion of
-derived NK exosomes as a potential therapeutic option alongside NK cell-based immunotherapy.
These findings highlight the therapeutic potential of NK cell-derived exosomes containing the tumor suppressor miR-186 that inhibits growth, spreading, and TGFβ-dependent immune escape mechanisms in neuroblastoma.
We re-estimate the peculiar velocity of the Sun with respect to the local standard of rest (LSR) using a sample of local stars within 600 pc of the Sun, selected from the Large Sky Area Multi-Object ...Fiber Spectroscopic Telescope (LAMOST, also named the Guoshoujing Telescope) Spectroscopic Survey of the Galactic Anti-centre (LSS-GAC). The sample consists of 94 332 FGK main-sequence stars with well-determined radial velocities and atmospheric parameters. To derive the LSR, two independent analyses are applied to the data. First, we determine the solar motion by comparing the observed velocity distribution to that generated with the analytic formulism of Schönrich & Binney that has been demonstrated to show excellent agreement with rigorous torus-based dynamics modelling by Binney & McMillan. Secondly, we propose that cold populations of thin disc stars, selected by applying an orbital eccentricity cut, can be directly used to determine the LSR without the need of asymmetric drift corrections. Both approaches yield consistent results of solar motion in the direction of Galactic rotation, V
⊙, that are much higher than the standard value adopted hitherto, derived from Strömgren's equation. The newly deduced values of V
⊙ are 1–2 km s−1 smaller than the more recent estimates derived from the Geneva–Copenhagen Survey (GCS) sample of stars in the solar neighbourhood (within 100 pc). We attribute the small difference to the presence of several well-known moving groups in the GCS sample that, fortunately, hardly affect the LSS-GAC sample. The newly derived radial (U
⊙) and vertical (W
⊙) components of the solar motion agree well with the previous studies. In addition, for all components of the solar motion, the values yielded by stars of different spectral types in the LSS-GAC sample are consistent with each other, suggesting that the local disc is well relaxed and that the LSR reported in the current work is robust. Our final recommended LSR is, (U⊙, V⊙, W⊙) = (7.01 ± 0.20, 10.13 ± 0.12, 4.95 ± 0.09) km s−1.
Classical Hodgkin lymphoma (cHL) is an unusual B-cell–derived malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an extensive but ineffective ...inflammatory/immune cell infiltrate. This striking feature suggests that malignant HRS cells escape immunosurveillance and interact with immune cells in the cancer microenvironment for survival and growth. We previously found that cHLs have a genetic basis for immune evasion: near-uniform copy number alterations of chromosome 9p24.1 and the associated PD-1 ligand loci, CD274/PD-L1 and PDCD1LG2/PD-L2, and copy number–dependent increased expression of these ligands. HRS cells expressing PD-1 ligands are thought to engage PD-1 receptor–positive immune effectors in the tumor microenvironment and induce PD-1 signaling and associated immune evasion. The genetic bases of enhanced PD-1 signaling in cHL make these tumors uniquely sensitive to PD-1 blockade.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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