| 71. |
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| 72. |
- Wang, HH, et al.
(författare)
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Prenatal High Estradiol Exposure Induces Sex-Specific and Dietarily Reversible Insulin Resistance Through Decreased Hypothalamic INSR
- 2018
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170. ; 159:1, s. 465-476
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Tidskriftsartikel (refereegranskat)abstract
- An adverse intrauterine environment may induce adult disease in offspring, but the mechanisms are not well understood. It is reported that fresh embryo transfer (ET) in assisted reproductive technology leads to high maternal estradiol (E2), and prenatal high E2 exposure increases the risk of organ disorders in later life. We found that male newborns and children of fresh ET showed elevated fasting insulin and homeostasis model of assessment for insulin resistance index (HOMA-IR) scores. Male mice with high prenatal estradiol exposure (HE) grew heavier than control mice and developed insulin resistance; they also showed increased food intake, with increased orexigenic hypothalamic neuropeptide Y (NPY) expression. The hypothalamic insulin receptor (INSR) was decreased in male HE mice, associated with elevated promoter methylation. Chronic food restriction (FR) in HE mice reversed insulin resistance and rescued hypothalamic INSR expression by correcting the elevated Insr promoter methylation. Our findings suggest that prenatal exposure to high E2 may induce sex-specific metabolic disorders in later life through epigenetic programming of hypothalamic Insr promoter, and dietary intervention may reverse insulin resistance by remodeling its methylation pattern.
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| 73. |
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| 74. |
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| 75. |
- Wang, T, et al.
(författare)
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Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 4932-
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Tidskriftsartikel (refereegranskat)abstract
- Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case–control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a total of 125 genes in over 16,000 NDD cases and compare the mutation burden to nonpsychiatric controls from ExAC. We identify 48 genes (25 newly reported) showing significant burden of ultra-rare (MAF < 0.01%) gene-disruptive mutations (FDR 5%), six of which reach family-wise error rate (FWER) significance (p < 1.25E−06). Among these 125 targeted genes, we also reevaluate DNM excess in 17,426 NDD trios with 6,499 new autism trios. We identify 90 genes enriched for DNMs (FDR 5%; e.g., GABRG2 and UIMC1); of which, 61 reach FWER significance (p < 3.64E−07; e.g., CASZ1). In addition to doubling the number of patients for many NDD risk genes, we present phenotype–genotype correlations for seven risk genes (CTCF, HNRNPU, KCNQ3, ZBTB18, TCF12, SPEN, and LEO1) based on this large-scale targeted sequencing effort.
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| 76. |
- Wang, YQ, et al.
(författare)
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A cell fitness selection model for neuronal survival during development
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4137-
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Tidskriftsartikel (refereegranskat)abstract
- Developmental cell death plays an important role in the construction of functional neural circuits. In vertebrates, the canonical view proposes a selection of the surviving neurons through stochastic competition for target-derived neurotrophic signals, implying an equal potential for neurons to compete. Here we show an alternative cell fitness selection of neurons that is defined by a specific neuronal heterogeneity code. Proprioceptive sensory neurons that will undergo cell death and those that will survive exhibit different molecular signatures that are regulated by retinoic acid and transcription factors, and are independent of the target and neurotrophins. These molecular features are genetically encoded, representing two distinct subgroups of neurons with contrasted functional maturation states and survival outcome. Thus, in this model, a heterogeneous code of intrinsic cell fitness in neighboring neurons provides differential competitive advantage resulting in the selection of cells with higher capacity to survive and functionally integrate into neural networks.
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| 77. |
- Wang, YQ, et al.
(författare)
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Muscle-selective RUNX3 dependence of sensorimotor circuit development
- 2019
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Ingår i: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 146:20
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Tidskriftsartikel (refereegranskat)abstract
- The control of all our motor outputs requires constant monitoring by proprioceptive sensory neurons (PSNs) that convey continuous muscle sensory inputs to the spinal motor network. Yet, the molecular programs that control the establishment of this sensorimotor circuit remain largely unknown. The transcription factor RUNX3 is essential for the early steps of PSNs differentiation, making it difficult to study its role during later aspects of PSNs specification. Here, we conditionally inactivate Runx3 in PSNs after peripheral innervation and identify that RUNX3 is necessary for maintenance of cell identity of only a subgroup of PSNs, without discernable cell death. RUNX3 controls also the sensorimotor connection between PSNs and motor neurons at limb level, with muscle-by-muscle variable sensitivities to the loss of Runx3 that correlate with levels of RUNX3 in PSNs. Finally, we find that muscles and neurotrophin-3 signaling are necessary for maintenance of RUNX3 expression in PSNs. Hence, a transcriptional regulator critical for specifying a generic PSN type identity after neurogenesis, is later regulated by target muscle-derived signal to contribute to the specialized aspects of the sensorimotor connection selectivity.
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| 78. |
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| 79. |
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| 80. |
- Wu, CZ, et al.
(författare)
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The Potential of Nano-Porous Surface Structure for Pain Therapeutic Applications: Surface Properties and Evaluation of Pain Perception
- 2020
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Ingår i: APPLIED SCIENCES-BASEL. - : MDPI AG. - 2076-3417. ; 10:13
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The objective of this study was to evaluate the biomaterial properties of nano-modified surface acupuncture needles and the effect of such needles on human pain perception by using pressure pain threshold (PPT) measurements. It is known that changing a material’s surface nano-topography or nanostructure has strong effects on its physical, chemical, and biological surface properties. However, there is no information in the literature about the stimulation characteristics of acupuncture needles with nano-topography or nanostructured surfaces. Based on the knowledge on nanostructured surfaces, it may be possible to potentiate the effects of acupuncture needle stimulation. The pressure pain sensitivity of the masseter muscle in the orofacial region was studied in 21 healthy volunteers in two randomized, double-blinded sessions: an active session of manual acupuncture manipulation with nano-modified surface needles, and an inactive session of sham acupuncture stimulation to control for possible placebo effects. Three acupuncture points were selected from classical Chinese medicine literature: LI4 (Hegu) on the hand, ST6 (Jiache) on the lower masseter region, and ST7 (Xiaguan) on the upper masseter region. PPT measurements, perceived sensations, and pain from the acupuncture were recorded. The results showed discrete yet significant differences in PPT values between the active and inactive acupuncture treatments and significantly higher pain scores from active acupuncture stimulation than from sham acupuncture. These results indicate subtle but significant effects of acupuncture stimulation with nano-modified surface needles, compared to sham acupuncture in healthy participants.
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