A bright γ-ray flare interpreted as a giant magnetar flare in NGC 253.

Soft γ-ray repeaters exhibit bursting emission in hard X-rays and soft γ-rays. During the active phase, they emit random short (milliseconds to several seconds long), hard-X-ray bursts, with peak luminosities1 of 1036 to 1043 erg per second. Occasionally, a giant flare with an energy of around 1044 to 1046 erg is emitted2. These phenomena are thought to arise from neutron stars with extremely high magnetic fields (1014 to 1015 gauss), called magnetars1,3,4. A portion of the second-long initial pulse of a giant flare in some respects mimics short γ-ray bursts5,6, which have recently been identified as resulting from the merger of two neutron stars accompanied by gravitational-wave emission7. Two γ-ray bursts, GRB 051103 and GRB 070201, have been associated with giant flares2,8-11. Here we report observations of the γ-ray burst GRB 200415A, which we localized to a 20-square-arcmin region of the starburst galaxy NGC 253, located about 3.5 million parsecs away. The burst had a sharp, millisecond-scale hard spectrum in the initial pulse, which was followed by steady fading and softening over 0.2 seconds. The energy released (roughly 1.3 × 1046 erg) is similar to that of the superflare5,12,13 from the Galactic soft γ-ray repeater SGR 1806-20 (roughly 2.3 × 1046 erg). We argue that GRB 200415A is a giant flare from a magnetar in NGC 253.

Moonshine: Diurnally varying hydration through natural distillation on the Moon, detected by the Lunar Exploration Neutron Detector (LEND).

The Lunar Exploration Neutron Detector (LEND), on the polar-orbiting Lunar Reconnaissance Orbiter (LRO) spacecraft, has detected suppression in the Moon's naturally-occurring epithermal neutron leakage flux that is consistent with the presence of diurnally varying quantities of hydrogen in the regolith near the equator. Peak hydrogen concentration (neutron flux suppression) is on the dayside of the dawn terminator and diminishes through the dawn-to-noon sector. The minimum concentration of hydrogen is in the late afternoon and dusk sector. The chemical form of hydrogen is not determinable from these measurements, but other remote sensing methods and anticipated elemental availability suggest water molecules or hydroxyl ions. Signal-to-noise ratio at maximum contrast is 5.6σ in each of two detector systems. Volatiles are deduced to collect in or on the cold nightside surface and distill out of the regolith after dawn as rotation exposes the surface to sunlight. Liberated volatiles migrate away from the warm subsolar region toward the nearby cold nightside surface beyond the terminator, resulting in maximum concentration at the dawn terminator. The peak concentration within the upper ~1 m of regolith is estimated to be 0.0125 ± 0.0022 weight-percent water-equivalent hydrogen (wt% WEH) at dawn, yielding an accumulation of 190 ± 30 ml recoverable water per square meter of regolith at each dawn. Volatile transport over the lunar surface in opposition to the Moon's rotation exposes molecules to solar ultraviolet radiation. The short lifetime against photolysis and permanent loss of hydrogen from the Moon requires a resupply rate that greatly exceeds anticipated delivery of hydrogen by solar wind implantation or by meteoroid impacts, suggesting that the surface inventory must be continually resupplied by release from a deep volatile inventory in the Moon. The natural distillation of water from the regolith by sunlight and its capture on the cold night surface may provide energy-efficient access to volatiles for in situ resource utilization (ISRU) by direct capture before volatiles can enter the surface, eliminating the need to actively mine regolith for volatile resource recovery.

Response to comment on "Hydrogen mapping of the lunar South Pole using the LRO neutron detector experiment LEND".

Critical comments from Lawrence et al. are considered on the capability of the collimated neutron telescope Lunar Exploration Neutron Detector (LEND) on NASA's Lunar Reconnaissance Orbiter (LRO) for mapping lunar epithermal neutrons, as presented in our paper. We present two different analyses to show that our previous estimated count rates are valid and support the conclusions of that paper.

Hydrogen mapping of the lunar south pole using the LRO neutron detector experiment LEND.

Hydrogen has been inferred to occur in enhanced concentrations within permanently shadowed regions and, hence, the coldest areas of the lunar poles. The Lunar Crater Observation and Sensing Satellite (LCROSS) mission was designed to detect hydrogen-bearing volatiles directly. Neutron flux measurements of the Moon's south polar region from the Lunar Exploration Neutron Detector (LEND) on the Lunar Reconnaissance Orbiter (LRO) spacecraft were used to select the optimal impact site for LCROSS. LEND data show several regions where the epithermal neutron flux from the surface is suppressed, which is indicative of enhanced hydrogen content. These regions are not spatially coincident with permanently shadowed regions of the Moon. The LCROSS impact site inside the Cabeus crater demonstrates the highest hydrogen concentration in the lunar south polar region, corresponding to an estimated content of 0.5 to 4.0% water ice by weight, depending on the thickness of any overlying dry regolith layer. The distribution of hydrogen across the region is consistent with buried water ice from cometary impacts, hydrogen implantation from the solar wind, and/or other as yet unknown sources.

Experiment LEND of the NASA Lunar Reconnaissance Orbiter for high-resolution mapping of neutron emission of the Moon.

The scientific objectives of neutron mapping of the Moon are presented as 3 investigation tasks of NASA's Lunar Reconnaissance Orbiter mission. Two tasks focus on mapping hydrogen content over the entire Moon and on testing the presence of water-ice deposits at the bottom of permanently shadowed craters at the lunar poles. The third task corresponds to the determination of neutron contribution to the total radiation dose at an altitude of 50 km above the Moon. We show that the Lunar Exploration Neutron Detector (LEND) will be capable of carrying out all 3 investigations. The design concept of LEND is presented together with results of numerical simulations of the instrument's sensitivity for hydrogen detection. The sensitivity of LEND is shown to be characterized by a hydrogen detection limit of about 100 ppm for a polar reference area with a radius of 5 km. If the presence of ice deposits in polar "cold traps" is confirmed, a unique record of many millions of years of lunar history would be obtained, by which the history of lunar impacts could be discerned from the layers of water ice and dust. Future applications of a LEND-type instrument for Mars orbital observations are also discussed.

SOCS1: a potent and multifaceted regulator of cytokines and cell-mediated inflammation.

Suppressor of cytokine signalling-1 (SOCS1), as the name implies, is a protein that functions as a negative regulator of cytokine signalling. Initially characterized for its ability to inhibit JAK phosphorylation and function, SOCS1 also targets proteins for degradation by the proteosome machinery. The expression of SOCS1 can be regulated at the transcription, translation and protein level. Despite the broad spectrum of cytokines that can induce SOCS1 expression and/or be inhibited by SOCS1 in vitro, the use of genetically modified mice has revealed a more specific role for SOCS1 in vivo including a critical role in the regulation of IFNgamma signalling. In addition, SOCS1 has a complex role in T cell activation, and studies have revealed significant roles for SOCS1 in the regulation of IL-4, IL-12 and IL-15 in vivo. Interestingly, SOCS1 action is not limited to the regulation of the classical JAK/STAT-signalling pathway, because SOCS1 also inhibits cytokines like insulin and toll-like receptor signal transduction, neither of which activates the JAK/STAT pathway. Evidence is emerging for a role for aberrant SOCS1 expression in human disease, particularly in a number of malignancies.

Structural and molecular pathology of the heart in Carvajal syndrome.

BACKGROUND: Carvajal syndrome is a familial cardiocutaneous syndrome consisting of woolly hair, palmoplantar keratoderma, and heart disease. It is caused by a recessive deletion mutation in desmoplakin, an intracellular protein that links desmosomal adhesion molecules to intermediate filaments of the cytoskeleton. The pathology of Carvajal syndrome has not been described. METHODS: Here, we report the first description of the structural and molecular pathology of the heart in Carvajal syndrome. We characterized gross and microscopic pathology and identified changes in expression and distribution of intercalated disk and intermediate filament proteins in ventricular myocardium. RESULTS: We identified a unique cardiomyopathy characterized by ventricular hypertrophy and dilatation, focal ventricular aneurysms, and distinct ultrastructural abnormalities of intercalated disks, but no evidence of fibrofatty infiltration or replacement of myocardium. We also observed markedly decreased amounts of specific immunoreactive signal for desmoplakin, plakoglobin, and the gap junction protein, connexin43, at intercalated disks. The intermediate filament protein, desmin, which is known to bind desmoplakin, showed a normal intracellular pattern of distribution but failed to localize at intercalated disks. CONCLUSIONS: The desmoplakin mutation in Carvajal syndrome produces a cardiomyopathy with unique pathologic features. Altered protein-protein interactions at intercalated disks likely cause both contractile and electrical dysfunction in Carvajal syndrome.

Remodeling of myocyte gap junctions in arrhythmogenic right ventricular cardiomyopathy due to a deletion in plakoglobin (Naxos disease).

OBJECTIVES: We tested the hypothesis that defective interactions between adhesion junctions and the cytoskeleton caused by the plakoglobin mutation in Naxos disease lead to remodeling of gap junctions and altered expression of the major gap junction protein, connexin43. BACKGROUND: Naxos disease, a recessive form of arrhythmogenic right ventricular cardiomyopathy, is associated with a high incidence of arrhythmias and sudden cardiac death. Naxos disease is caused by a mutation in plakoglobin, a protein that links cell-cell adhesion molecules to the cytoskeleton. METHODS: Myocardial expression of connexin43 and other intercellular junction proteins was characterized in 4 patients with Naxos disease. Immunohistochemistry was performed in all 4 patients, and immunoblotting and electron microscopy were performed in 1 patient who died in childhood before overt arrhythmogenic right ventricular cardiomyopathy had developed. RESULTS: Connexin43 expression at intercellular junctions was reduced significantly in both right and left ventricles in all patients with Naxos disease. Electron microscopy revealed smaller and fewer gap junctions interconnecting ventricular myocytes. Mutant plakoglobin was expressed but failed to localize normally at intercellular junctions. Localization of N-cadherin, alpha- and beta-catenins, plakophilin-2, desmoplakin-1, and desmocollin-2 at intercalated disks appeared normal. CONCLUSIONS: Remodeling of gap junctions occurs early in Naxos disease, presumably because of abnormal linkage between mechanical junctions and the cytoskeleton. Gap junction remodeling may produce a coupling defect which, combined with the subsequent development of pathologic changes in myocardium, could contribute to a highly arrhythmogenic substrate and enhance the risk of sudden death in Naxos disease.

Functional expression cloning reveals proapoptotic role for protein phosphatase 4.

Functional expression cloning strategies are highly suitable for the analysis of the molecular control of apoptosis. This approach has two critical advantages. Firstly, it eliminates prior assumptions about the properties of the proteins involved, and, secondly, it selectively targets proteins that are causally involved in apoptosis control and which affect the crucial cellular decision between survival and death. The application of this strategy to the isolation of cDNAs conferring resistance to dexamethasone and gamma-irradiation resulted in the isolation of a partial cDNA for the catalytic subunit of protein phosphatase 4 (PP4). Cells transfected with this partial cDNA in an expression vector downregulated PP4 and were resistant to both dexamethasone and UV radiation, as demonstrated by both membrane integrity and colony-forming assays. These observations suggest that PP4 plays an important proapoptotic role in T lymphocytes.

Distribution of hydrogen in the near surface of Mars: evidence for subsurface ice deposits.

Using the Gamma-Ray Spectrometer on the Mars Odyssey, we have identified two regions near the poles that are enriched in hydrogen. The data indicate the presence of a subsurface layer enriched in hydrogen overlain by a hydrogen-poor layer. The thickness of the upper layer decreases with decreasing distance to the pole, ranging from a column density of about 150 grams per square centimeter at -42 degrees latitude to about 40 grams per square centimeter at -77 degrees. The hydrogen-rich regions correlate with regions of predicted ice stability. We suggest that the host of the hydrogen in the subsurface layer is ice, which constitutes 35 +/- 15% of the layer by weight.

SOCS1 regulates interferon-gamma mediated sensory neuron survival.

Differentiation and survival of sensory neurons is regulated by factors such as NGF and LIF. Regulation of signal transduction pathways downstream of such factor signalling by suppressor of cytokine signalling (SOCS) proteins, which negatively regulate the JAK/STAT pathway, may modulate biological outcome. In this study, SOCS1 regulation of growth factor mediated sensory neuron survival was examined. SOCS1 expression by sensory neurons was up-regulated by IFNgamma. Survival of sensory neurons from SOCS1 null mice in NGF or LIF was similar to wildtype mice. IFNgamma partially supported survival of wildtype neurons but supported survival of SOCS1 null neurons as effectively as NGF or LIF. Thus it appears that SOCS1 is a major regulator of sensory neuron responses to the inflammatory cytokine, IFNgamma.

The SOCS box of suppressor of cytokine signaling-1 is important for inhibition of cytokine action in vivo.

Suppressor of Cytokine Signaling-1 (SOCS-1) is an essential physiological inhibitor of IFN-gamma signaling. Mice lacking this gene die in the early postnatal period from a disease characterized by hyperresponsiveness to endogenous IFN-gamma. The SOCS box is a C-terminal domain shared with over 30 other proteins that links SOCS proteins to an E3 ubiquitin ligase activity and the proteasome, but whether it contributes to inhibition of cytokine signaling is currently disputed. We have deleted only the SOCS box of the SOCS-1 gene in mice and show that such mice have an increased responsiveness to IFN-gamma and slowly develop a fatal inflammatory disease. These results demonstrate that deletion of the SOCS box leads to a partial loss of function of SOCS-1.

A comparison of overground and treadmill running for measuring the three-dimensional kinematics of the lumbo-pelvic-hip complex.

OBJECTIVE: To compare overground and treadmill running for differences in the three-dimensional angular kinematics of the lumbo-pelvic-hip complex. DESIGN: A within-subject repeated measures design. BACKGROUND: The treadmill is an attractive research instrument as speed and slope are easily controlled and the required calibration volume is reduced. However, the degree to which treadmill running simulates overground running has not been resolved in the literature to date. METHODS: 10 able-bodied subjects ran overground and on a treadmill at a self-selected speed. The treadmill speed was matched to each subjects respective average overground speed. The time-distance and the three-dimensional angular kinematic data were captured using a passive marker based motion analysis system. A set of angular and temporal kinematic parameters were extracted from the data and subjected to statistical analyses. RESULTS: Significant differences were found between overground and treadmill running for all the time-distance parameters. Despite this, the kinematics of the lumbar spine and pelvis were similar between the two running conditions, with only three parameters being significantly different. These were lumbar extension at initial contact, anterior pelvic tilt at initial contact and the first maximum anterior pelvic tilt. Hip flexion-extension parameters were also only found to display subtle differences. Of the 17 hip parameters analysed, only hip flexion at initial contact, maximum hip flexion at loading response, hip extension at toe off, maximum hip extension and hip flexion-extension range of motion were found to be significantly different. CONCLUSION: A high powered treadmill with a minimal belt speed fluctuation is capable of being used to obtain a representation of the typical three-dimensional kinematic pattern of the lumbo-pelvic-hip complex during running. RELEVANCE: In order for the treadmill to be accepted as a useful research and/or clinical assessment instrument, it must be demonstrated that it does not significantly alter the performance of the evaluated activity. In this respect, a treadmill with minimal intra-stride belt speed variability and similar surface stiffness to the relevant overground condition is likely to be capable of being used to obtain a representation of the typical human running action for well accommodated subjects.

The effect of differing Cardan angle sequences on three dimensional lumbo-pelvic angular kinematics during running.

The variability in the three dimensional (3D) lumbo-pelvic angular kinematic patterns during running when using differing Cardan angle sequences was quantified. Data for four able-bodied subjects running on a treadmill at 4.0 m/s were captured using a motion analysis system with six cameras operating at 200 Hz. The adjusted coefficient of multiple correlation was used to compare graphical waveforms whilst the maximum root mean square of the differences was used to express the magnitude of any discrepancy in absolute units. Minimal qualitative differences were found between the various sequences. Quantitative differences between each of the Cardan angle sequences were not found to exceed 7.0 degrees and 2.8 degrees for the lumbar spine and pelvic rotations respectively. It was concluded that different Cardan angle sequences were not found to substantially affect typical 3D lumbo-pelvic angular kinematic patterns during running.

SOCS1 deficiency results in accelerated mammary gland development and rescues lactation in prolactin receptor-deficient mice.

Prolactin is essential for proliferation and differentiation of the developing mammary gland. We have explored a role for Suppressor of Cytokine Signaling 1 (SOCS1) as a modulator of the prolactin response using mice deficient in SOCS1, which were rescued from neonatal death by deletion of the Interferon gamma (IFN gamma) gene. SOCS1(-/-)/IFN gamma(-/-) mice exhibited accelerated lobuloalveolar development in the mammary gland during late pregnancy and precocious lactation. Significantly, the lactogenic defect in prolactin receptor heterozygous females could be rescued by deletion of a single SOCS1 allele. These findings establish a role for SOCS1 as a negative regulator of prolactin signaling and suggest that SOCS1 is required for the prevention of lactation prior to parturition.

Type and timing of mothers' victimization: effects on mothers and children.

OBJECTIVES: There is mounting concern about how mothers' own victimization experiences affect their children. This study examines the effects of mothers' victimization on their own mental health and parenting and on their children's behavior, development, and health. The effects of both timing and type of victimization are assessed. A related objective was to determine if there was a cumulative risk effect produced by victimization during both childhood and adulthood, or both physical and sexual. SETTING: Urban families in an eastern state and urban and rural families in a southern state. PARTICIPANTS: A total of 419 mothers and their children 6 to 7 years old were identified from 2 sites. The eastern sample was recruited in the first 2 years of life from 3 pediatric clinics: 1 for children at high risk for human immunodeficiency virus disease, 1 for children with failure to thrive, and a third providing pediatric primary care. The southern sample was derived from a cohort of children at risk for adverse health or developmental outcomes, plus a systematic sampling of controls, recruited from area hospitals. At age 4, a random sample of children from the original cohort who had been maltreated along with a matched comparison group of nonmaltreated children were selected. RESULTS: In general, mothers victimized during both childhood and adulthood had poorer outcomes than mothers victimized during either childhood/adolescence or adulthood who in turn had worse outcomes than mothers with no history of victimization. This manifested as more maternal depressive symptoms, harsher parenting, and more externalizing and internalizing behavior problems in their children. There were no significant differences in maternal functioning or child outcomes between those abused in childhood and those abused in adulthood. These findings were similar for type of victimization. Mothers' depression and harsh parenting were directly associated with their children's internalizing and externalizing behavior problems. CONCLUSIONS: Maternal victimization appears to be a highly prevalent problem in high-risk samples and is associated with harmful implications for mental health and parenting, as well as for the offspring. Pediatricians need to consider past and current victimization of mothers. Routine screening for these problems, followed by appropriate evaluation and intervention may reduce maternal depression, improve parenting, and reduce the incidence of behavior problems in children.

Suppressor of cytokine signaling-1 attenuates the duration of interferon gamma signal transduction in vitro and in vivo.

Suppressor of cytokine signaling-1 (SOCS-1) is a cytokine-inducible intracellular protein that functions to negatively regulate cytokine signal transduction pathways. Studies in vitro have shown that constitutive overexpression of SOCS-1 inhibits signaling in response to a range of cytokines, including interferons (IFN). Mice lacking SOCS-1 die from a complex disease characterized by liver degeneration and massive inflammation. Whereas there is clear evidence of increased IFNgamma signaling in SOCS-1(-/-) mice, it is unclear to what extent this is due to increased IFNgamma levels or to increased IFNgamma sensitivity. Here we have used SOCS-1(-/-) IFNgamma(-/-) mice, which remain healthy and produce no endogenous IFNgamma, to demonstrate that in vitro and in vivo hepatocytes lacking SOCS-1 exhibit a prolonged response to IFNgamma and that this correlates with a dramatically increased sensitivity to the toxic effects of IFNgamma in vivo. Thus, SOCS-1 is required for the timely attenuation of IFNgamma signaling in vivo.

Gigantism in mice lacking suppressor of cytokine signalling-2.

Suppressor of cytokine signalling-2 (SOCS-2) is a member of the suppressor of cytokine signalling family, a group of related proteins implicated in the negative regulation of cytokine action through inhibition of the Janus kinase (JAK) signal transducers and activators of transcription (STAT) signal-transduction pathway. Here we use mice unable to express SOCS-2 to examine its function in vivo. SOCS-2(-/-) mice grew significantly larger than their wild-type littermates. Increased body weight became evident after weaning and was associated with significantly increased long bone lengths and the proportionate enlargement of most organs. Characteristics of deregulated growth hormone and insulin-like growth factor-I (IGF-I) signalling, including decreased production of major urinary protein, increased local IGF-I production, and collagen accumulation in the dermis, were observed in SOCS-2-deficient mice, indicating that SOCS-2 may have an essential negative regulatory role in the growth hormone/IGF-I pathway.