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The absolute value of stress on a fault during slip is a critical unknown quantity in earthquake physics. One of the reasons for the uncertainty is a lack of geological constraints in real faults. Here we calculate the slip rate and stress on an ancient fault in a new way based on rocks preserved in an unusual exposure. The study area consists of a fault core on Kodiak Island that has a series of asymmetrical intrusions of ultrafine‐grained fault rock into the surrounding cataclasite. The intrusive structures have ductile textures and emanate upward from a low‐density layer. We interpret the intrusions as products of a gravitational (Rayleigh‐Taylor) instability where the spacing between intrusions reflects the preferred wavelength of the flow. The spacing between intrusions is 1.4 ± 0.5 times the thickness of the layer. This low spacing‐to‐thickness ratio cannot be explained by a low Reynolds number flow but can be generated by one with moderate Reynolds numbers. Using a range of density contrasts and the geometry of the outcrop as constraints, we find that the distance between intrusions is best explained by moderately inertial flow with fluid velocities on the order of 10 cm/s. The angle that the intrusions are bent over implies that the horizontal slip velocity was comparable to the vertical rise velocity, and therefore, the fault was slipping at a speed of order 10 cm/s during emplacement. These slip velocities are typical of an earthquake or its immediate afterslip and thus require a coseismic origin. The Reynolds number of the buoyant flow requires a low viscous stress of at most 20 Pa during an earthquake.

This article examines how parental education level moderates the genetic and environmental contributions to variation in verbal IQ. Data are from 1909 non-Hispanic Whites and African American sibling pairs from the National Longitudinal Study of Adolescent Health, which obtained nationally-based samples of identical (MZ) twins, fraternal (DZ) twins, full and half siblings, cousins (in the same household), and biologically unrelated siblings. In the whole sample, the variance estimate for heritability (h2 = .57, SE = .08) was greater than that for shared environment (c2 = .13, SE = .04). Both heritability and the shared environmental estimate were moderated, however, by level of parental education. Specifically, among more highly educated families, the average h2 = .74 (SE = .10) and the average c2 = .00 (SE = .05). Conversely, among less well-educated families, heritability decreased and shared environmental influences increased, yielding similar proportions of variance explained by genetic and environmental factors, average h2 = .26 (SE = .15), and average c2 = .23 (SE = .07).

A polymorphism in the dopamine receptor 4 gene (DRD4) has been related to novelty seeking, Tourette's syndrome, and attention deficit hyperactivity disorder (ADHD). The variability is in a 48-bp repeat in exon 3 of the gene (a transmembrane region). This study examined the relation of the 7-repeat (ie, high-risk) allele to questionnaire-based diagnoses of ADHD (both combined type and inattentive type). Several positive findings were obtained for ADHD-inattentive type. In an association test, the 7-repeat allele occurred more frequently in children with ADHD-inattentive type than in control children. In genetically discordant sibling pairs, the sibling with a greater number of 7-repeat alleles displayed more inattentive symptoms than his/her co-sibling with fewer 7-repeat alleles. For ADHD-combined type, the 7-repeat allele frequency was greater than that in the control sample. However, a quantitative transmission disequilibrium test yielded no significant linkage of the 7-repeat allele with hyperactive-impulsive symptoms. A categorical TDT yielded no significant findings, but the number of transmissions was small, especially for ADHD-inattentive type.

The 7-repeat allele of the dopamine receptor D4 gene (DRD4) and the 10 repeat allele of the dopamine transporter gene (DAT1) have shown association and linkage with symptoms of attention deficit hyperactivity disorder (ADHD) in childhood. The parents of ADHD children (clinic group, n = 80 fathers and 107 mothers) and control children (control group, n = 42 fathers and 51 mothers) were the focus of this study. These parents reported retrospectively on their level of ADHD Inattention and Conduct Disorder symptoms in adolescence. In analyses of the relation of symptom levels to the DRD4 and DAT1 genotypes, fathers possessing the 7 repeat DRD4 allele had greater levels of both inattention and conduct disorder symptoms. Mothers with the 10/10 genotype had higher levels of inattention symptoms. Thus, genetic associations found in children may be replicable in their parents.

This study investigated the relationship between depressive symptom response during tryptophan (TRP) depletion and a functional polymorphism of the promoter region of the serotonin (5-HT) transporter gene (SLC6A4).(1) Forty-three subjects in remission from a major depressive episode who underwent TRP depletion were genotyped. DNA was extracted from blood lymphocytes or from cheek cells.(2) The two common alleles are designated long (l) and short (s). Depressive symptoms were measured with the 25-item Hamilton Depression Rating Scale (HDRS).(3) There was a significant association between the l homozygous genotype and the depressive response to TRP depletion, with a significant main effect of time (F = 8.763, df = 3, 38, P = <0.001), and time x l homozygous allele interaction (F = 3.676, df = 3, 38, P = 0.02). Individuals whose genotype predicted increased 5-HT transporter activity may be more susceptible to depressive changes in response to transient 5-HT perturbations. The use of endophenotypic markers for affective disorders such as the mood response to TRP depletion may facilitate studies of complex genetic traits such as depression by decreasing its heterogeneity.

The transcription factors interferon regulatory factor 3 (IRF3) and NF-κB are required for the expression of many genes involved in the innate immune response. Viral infection, or the binding of double-stranded RNA to Toll-like receptor 3, results in the coordinate activation of IRF3 and NF-κB. Activation of IRF3 requires signal-dependent phosphorylation, but little is known about the signaling pathway or kinases involved. Here we report that the noncanonical IκB kinase homologs, IκB kinase-ε (IKKε) and TANK-binding kinase-1 (TBK1), which were previously implicated in NF-κB activation, are also essential components of the IRF3 signaling pathway. Thus, IKKε and TBK1 have a pivotal role in coordinating the activation of IRF3 and NF-κB in the innate immune response.

Virus infection, double-stranded RNA, and lipopolysaccharide each induce the expression of genes encoding IFN-α and -β and chemokines, such as RANTES (regulated on activation, normal T cell expressed and secreted) and IP-10 (IFN-γ, inducible protein 10). This induction requires the coordinate activation of several transcription factors, including IFN-regulatory factor 3 (IRF3). The signaling pathways leading to IRF3 activation are triggered by the binding of pathogen-specific products to Toll-like receptors and culminate in the phosphorylation of specific serine residues in the C terminus of IRF3. Recent studies of human cell lines in culture have implicated two noncanonical Iκ B kinase (IKK)-related kinases, IKK-ε and Traf family member-associated NF-κ B activator (TANK)-binding kinase 1 (TBK1), in the phosphorylation of IRF3. Here, we show that purified recombinant IKK-ε and TBK1 directly phosphorylate the critical serine residues in IRF3. We have also examined the expression of IRF3-dependent genes in mouse embryonic fibroblasts (MEFs) derived from Tbk1-/-mice, and we show that TBK1 is required for the activation and nuclear translocation of IRF3 in these cells. Moreover, Tbk1-/-MEFs show marked defects in IFN-α and -β, IP-10. and RANTES gene expression after infection with either Sendai or Newcastle disease viruses or after engagement of the Toll-like receptors 3 and 4 by double-stranded RNA and lipopolysaccharide, respectively. Finally, TRIF (TIR domain-containing adapter-inducing IFN-β), fails to activate IRF3-dependent genes in Tbk1-/-MEFs. We conclude that TBK1 is essential for IRF3-dependent antiviral gene expression.