Polycystic ovary syndrome (PCOS) is a common endocrine disorder of women, characterized by hyperandrogenism and chronic anovulation. It is a leading cause of female infertility and is associated with ...polycystic ovaries, hirsutism, obesity, and insulin resistance. We tested a carefully chosen collection of 37 candidate genes for linkage and association with PCOS or hyperandrogenemia in data from 150 families. The strongest evidence for linkage was with the follistatin gene, for which affected sisters showed increased identity by descent (72%; χ 2 = 12.97; nominal P=3.2× 10-4). After correction for multiple testing (33 tests), the follistatin findings were still highly significant (Pc=0.01). Although the linkage results for CYP11A were also nominally significant (P = 0.02), they were no longer significant after correction. In 11 candidate gene regions, at least one allele showed nominally significant evidence for population association with PCOS in the transmission/disequilibrium test (χ 2 ≥ 3.84; nominal $P<0.05)$. The strongest effect in the transmission/disequilibrium test was observed in the INSR region (D19S884; allele 5; χ 2=8.53) but was not significant after correction. Our study shows how a systematic screen of candidate genes can provide strong evidence for genetic linkage in complex diseases and can identify those genes that should have high (or low) priority for further study.
The human growth hormone family of peptide hormones is encoded by five genes, pituitary growth hormone (hGH-N), and four placentally expressed genes, growth hormone variant (hGH-V), chorionic ...somatomammotropin A and B (hCS-A, hCS-B), and prolactin (hPrl). As part of an effort to define the local effects of the placentally expressed members of the GH/Prl family of hormones on the placenta, we have identified an isoform (hGHRd3) of the growth hormone receptor expressed in the placental villi. hGHRd3 mRNA differs from the liver GHR mRNA by the deletion of a 66-base pair segment encoding exon 3. In this study we show that hGHRd3 mRNA encodes a stable and functional receptor. hGHRd3 mRNA is efficiently translated and processed in a rabbit reticulocyte lysate translation system as well as in an in vivo Xenopus laevis oocyte expression system. In Xenopus oocytes hGHRd3 is stably integrated into the cell membrane and binds and internalizes ligand as efficiently as hGHR. hGHRd3 binds all three of the placentally expressed members of the GH/Prl gene family (hGH-V, hCS, and Prl) as well as both the 22 and 20 kDa isoforms of the pituitary hGH-N. The results of the present study strongly support the expression of a functional hGHRd3 isoreceptor in the placenta which may serve in autocrine, paracrine, and/or endocrine activation.
Interstitial collagen gives fetal membranes tensile strength, and membrane rupture has been attributed to collagen degradation. A polymorphism at −1607 in the matrix metalloproteinase-1 (MMP-1) ...promoter (an insertion of a guanine (G)) creates a core Ets binding site and increases promoter activity. We investigated whether this polymorphism is functionally significant for MMP-1 expression in amnion cells and whether it is associated with preterm premature rupture of the membranes (PPROM). The 2G promoter had >2-fold greater activity than the 1G allele in amnion mesenchymal cells and WISH amnion cells. Phorbol 12-myristate 13-acetate (PMA) increased mesenchymal cell nuclear protein binding with greater affinity to the 2G allele. Induction of MMP-1 mRNA by PMA was significantly greater in cells with a 1G/2G or 2G/2G genotype compared with cells homozygous for the 1G allele. When treated with PMA, the 1G/2G and 2G/2G cells produced greater amounts of MMP-1 protein than 1G/1G cells. A significant association was found between fetal carriage of a 2G allele and PPROM. We conclude that the 2G allele has stronger promoter activity in amnion cells, that it confers increased responsiveness of amnion cells to stimuli that induce MMP-1, and that this polymorphism contributes to the risk of PPROM.
BackgroundPreterm brain injury causes neurodevelopmental disability. Excitotoxicity plays an important role in the pathogenesis of preterm brain injury. The neuropeptide secretoneurin (SN) was shown ...to enhance angiogenesis and neurogenesis in a rodent model of adult ischaemic brain damage. SN might be considered a promising substance in newborn brain injury.AimTo evaluate the effect of SN as a therapeutic strategy in an established in vivo model of excitotoxic newborn brain injury.MethodsFive-day-old mice pups were subjected to an intracranial injection of ibotenic acid into the right brain hemisphere. After recovery for one hour, animals were randomly treated with an intraperitoneal injection of i) vehicle, ii) SN 0.25 mu g/g body weight (bw) or iii) SN 2.5 mu g/g bw. Brains were harvested 24 and 120 h after the insult and processed for histological analysis. As a primary outcome parameter lesion size in cortical grey and white matter was evaluated.ResultsSN administration had no significant effect on lesion size 120 h after the insult. When evaluated 24 h after the excitotoxic insult, SN showed a marked, but non-significant trend towards a decreased lesion size in white matter (SN 0.25 mu g/g 323.33 plus or minus 128.82, SN 2.5 mu g/g bw 298.46 plus or minus 137.46, vehicle 440.00 plus or minus 227.81, n = 13-19, p = 0.06). SN had no effect on lesion size in grey matter.ConclusionThis study shows a trend towards a reduced injury in white matter in an in vivo model of neonatal brain injury. We are currently performing immunohistochemical analysis to evaluate underlying mechanisms that could result in long-term protection.
We have used time-resolved x-ray photoemission electron microscopy to investigate the magnetization dynamics induced by nanosecond current pulses in NiFe/Cu/Co nanostripes. A large tilt of the NiFe ...magnetization in the direction transverse to the stripe is observed during the pulses. We show that this effect cannot be quantitatively understood from the amplitude of the Oersted field and the shape anisotropy. High frequency oscillations observed at the onset of the pulses are attributed to precessional motion of the NiFe magnetization about the effective field. We discuss the possible origins of the large magnetization tilt and the potential implications of the static and dynamic effects of the Oersted field on current-induced domain wall motion in such stripes.
Assembling and maintaining large arrays of individually addressable atoms is a key requirement for continued scaling of neutral-atom-based quantum computers and simulators. In this work, we ...demonstrate a new paradigm for assembly of atomic arrays, based on a synergistic combination of optical tweezers and cavity-enhanced optical lattices, and the incremental filling of a target array from a repetitively filled reservoir. In this protocol, the tweezers provide microscopic rearrangement of atoms, while the cavity-enhanced lattices enable the creation of large numbers of optical traps with sufficient depth for rapid low-loss imaging of atoms. We apply this protocol to demonstrate near-deterministic filling (99% per-site occupancy) of 1225-site arrays of optical traps. Because the reservoir is repeatedly filled with fresh atoms, the array can be maintained in a filled state indefinitely. We anticipate that this protocol will be compatible with mid-circuit reloading of atoms into a quantum processor, which will be a key capability for running large-scale error-corrected quantum computations whose durations exceed the lifetime of a single atom in the system.
Assembling and maintaining large arrays of individually addressable atoms is a key requirement for continued scaling of neutral-atom-based quantum computers and simulators. In this work, we ...demonstrate a new paradigm for assembly of atomic arrays, based on a synergistic combination of optical tweezers and cavity-enhanced optical lattices, and the incremental filling of a target array from a repetitively filled reservoir. In this protocol, the tweezers provide microscopic rearrangement of atoms, while the cavity-enhanced lattices enable the creation of large numbers of optical traps with sufficient depth for rapid low-loss imaging of atoms. We apply this protocol to demonstrate near-deterministic filling (99% per-site occupancy) of 1225-site arrays of optical traps. Because the reservoir is repeatedly filled with fresh atoms, the array can be maintained in a filled state indefinitely. We anticipate that this protocol will be compatible with mid-circuit reloading of atoms into a quantum processor, which will be a key capability for running large-scale error-corrected quantum computations whose durations exceed the lifetime of a single atom in the system. Published by the American Physical Society 2024
Measurement-based quantum error correction relies on the ability to determine the state of a subset of qubits (ancillas) within a processor without revealing or disturbing the state of the remaining ...qubits. Among neutral-atom-based platforms, a scalable, high-fidelity approach to midcircuit measurement that retains the ancilla qubits in a state suitable for future operations has not yet been demonstrated. In this work, we perform maging using a narrow-linewidth transition in an array of tweezer-confined ^{171}Yb atoms to demonstrate nondestructive state-selective and site-selective detection. By applying site-specific light shifts, selected atoms within the array can be hidden from imaging light, which allows a subset of qubits to be measured while causing only percent-level errors on the remaining qubits. As a proof-of-principle demonstration of conditional operations based on the results of the midcircuit measurements, and of our ability to reuse ancilla qubits, we perform conditional refilling of ancilla sites to correct for occasional atom loss, while maintaining the coherence of data qubits. Looking toward true continuous operation, we demonstrate loading of a magneto-optical trap with a minimal degree of qubit decoherence.
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