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Accessory mineral microstructure and chronology reveals no evidence for late heavy bombardment on the asteroid 4-Vesta
A long-standing paradigm in planetary science is that the inner Solar System experienced a period of intense and sustained bombardment between 4.2 and 3.9 Ga. Evidence of this period, termed the Late Heavy Bombardment is provided by the 40Ar/39Ar isotope systematics of returned Apollo samples, lunar meteorites, and asteroidal meteorites. However, it has been largely unsupported by more recent and robust isotopic age data, such as isotopic age data obtained using the U-Pb system. Here we conduct careful microstructural characterisation of baddeleyite, zircon, and apatite in six different eucrites prior to conducting SIMS and LA-ICP-MS measurement of U, Th, and Pb isotopic ratios and radiometric dating. Baddeleyite, displaying complex internal twinning linked to reversion from a high symmetry polymorph in two samples, records the formation of the parent body (4554 Ā± 3 Ma 2Ļ; n = 8), while structurally simple zircon records a tight spread of ages representing metamorphism between 4574 Ā± 14 Ma and 4487 Ā± 31 Ma (n = 6). Apatite, a more readily reset shock chronometer, records crystallisation ages of ā¼4509 Ma (n = 6), with structurally deformed grains (attributed to impact events) yielding U-Pb ages of 4228 Ma (n = 12). In concert, there is no evidence within the measured U-Pb systematics or microstructural record of the eucrites examined in this study to support a period of late heavy bombardment between 4.2 and 3.9 Ga
Psychosocial Treatment of Children in Foster Care: A Review
A substantial number of children in foster care exhibit psychiatric difficulties. Recent epidemiologi-cal and historical trends in foster care, clinical findings about the adjustment of children in foster care, and adult outcomes are reviewed, followed by a description of current approaches to treatment and extant empirical support. Available interventions for these children can be categorized as either symptom-focused or systemic, with empirical support for specific methods ranging from scant to substantial. Even with treatment, behavioral and emotional problems often persist into adulthood, resulting in poor functional outcomes. We suggest that self-regulation may be an important mediat-ing factor in the appearance of emotional and behavioral disturbance in these children
Progress in muscular dystrophy research with special emphasis on gene therapy
Duchenne muscular dystrophy (DMD) is an X-linked, progressive muscle-wasting disease caused by mutations in the DMD gene. Since the disease was described by physicians in the 19th century, information about the subject has been accumulated. One author (Sugita) was one of the coworkers who first reported that the serum creatine kinase (CK) level is elevated in progressive muscular dystrophy patients. Even 50 years after that first report, an elevated serum CK level is still the most useful marker in the diagnosis of DMD, a sensitive index of the state of skeletal muscle, and useful to evaluate therapeutic effects. In the latter half of this article, we describe recent progress in the therapy of DMD, with an emphasis on gene therapies, particularly exon skipping
CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice
Neuroinflammation and microglial activation are significant processes in Alzheimer's disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer's disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer's disease and other tau-mediated neurodegenerative diseases
Inflammatory biomarkers in Alzheimer's disease plasma
Introduction: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a \u201cHoly Grail\u201d of AD research and intensively sought; however, there are no well-established plasma markers. Methods: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed. Results: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APO\u3b54 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71). Discussion: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation
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