Fault Slip and Exhumation History of the Willard Thrust Sheet, Sevier Fold‐Thrust Belt, Utah: Relations to Wedge Propagation, Hinterland Uplift, and Foreland Basin Sedimentation

Zircon (U‐Th)/He (ZHe) and zircon fission track thermochronometric data for 47 samples spanning the areally extensive Willard thrust sheet within the western part of the Sevier fold‐thrust belt record enhanced cooling and exhumation during major thrust slip spanning approximately 125–90 Ma. ZHe and zircon fission track age‐paleodepth patterns along structural transects and age‐distance relations along stratigraphic‐parallel traverses, combined with thermo‐kinematic modeling, constrain the fault slip history, with estimated slip rates of ~1 km/Myr from 125 to 105 Ma, increasing to ~3 km/Myr from 105 to 92 Ma, and then decreasing as major slip was transferred onto eastern thrusts. Exhumation was concentrated during motion up thrust ramps with estimated erosion rates of ~0.1 to 0.3 km/Myr. Local cooling ages of approximately 160–150 Ma may record a period of regional erosion, or alternatively an early phase of limited... (see full abstract in article)

Extending Phenomenological Crystal-Field Methods to C1C_1 Point-Group Symmetry: Characterization of the Optically-Excited Hyperfine Structure of 167^{167}Er3+^{3+}:Y2_2SiO5_5

We show that crystal-field calculations for $C_1$ point-group symmetry are possible, and that such calculations can be performed with sufficient accuracy to have substantial utility for rare-earth based quantum information applications. In particular, we perform crystal-field fitting for a C$_1$-symmetry site in $^{167}$Er$^{3+}$:Y$_2$SiO$_5$. The calculation simultaneously includes site-selective spectroscopic data up to 20,000 cm$^{-1}$, rotational Zeeman data, and ground- and excited-state hyperfine structure determined from high-resolution Raman-heterodyne spectroscopy on the 1.5 $\mu$m telecom transition. We achieve an agreement of better than 50 MHz for assigned hyperfine transitions. The success of this analysis opens the possibility of systematically evaluating the coherence properties, as well as transition energies and intensities, of any rare-earth ion doped into Y$_2$SiO$_5$ .Comment: 6 pages, plus 5 pages in supplementary information, 4 figures tota

Dysfunction of cortical GABAergic neurons leads to sensory hyper-reactivity in a Shank3 mouse model of ASD.

Hyper-reactivity to sensory input is a common and debilitating symptom in individuals with autism spectrum disorders (ASD), but the neural basis underlying sensory abnormality is not completely understood. Here we examined the neural representations of sensory perception in the neocortex of a Shank3B-/- mouse model of ASD. Male and female Shank3B-/- mice were more sensitive to relatively weak tactile stimulation in a vibrissa motion detection task. In vivo population calcium imaging in vibrissa primary somatosensory cortex (vS1) revealed increased spontaneous and stimulus-evoked firing in pyramidal neurons but reduced activity in interneurons. Preferential deletion of Shank3 in vS1 inhibitory interneurons led to pyramidal neuron hyperactivity and increased stimulus sensitivity in the vibrissa motion detection task. These findings provide evidence that cortical GABAergic interneuron dysfunction plays a key role in sensory hyper-reactivity in a Shank3 mouse model of ASD and identify a potential cellular target for exploring therapeutic interventions

Aerosol-jet printing facilitates the rapid prototyping of microfluidic devices with versatile geometries and precise channel functionalization.

Microfluidics has emerged as a powerful analytical tool for biology and biomedical research, with uses ranging from single-cell phenotyping to drug discovery and medical diagnostics, and only small sample volumes required for testing. The ability to rapidly prototype new designs is hugely beneficial in a research environment, but the high cost, slow turnaround, and wasteful nature of commonly used fabrication techniques, particularly for complex multi-layer geometries, severely impede the development process. In addition, microfluidic channels in most devices currently play a passive role and are typically used to direct flows. The ability to "functionalize" the channels with different materials in precise spatial locations would be a major advantage for a range of applications. This would involve incorporating functional materials directly within the channels that can partake in, guide or facilitate reactions in precisely controlled microenvironments. Here we demonstrate the use of Aerosol Jet Printing (AJP) to rapidly produce bespoke molds for microfluidic devices with a range of different geometries and precise "in-channel" functionalization. We show that such an advanced microscale additive manufacturing method can be used to rapidly design cost-efficient and customized microfluidic devices, with the ability to add functional coatings at specific locations within the microfluidic channels. We demonstrate the functionalization capabilities of our technique by specifically coating a section of a microfluidic channel with polyvinyl alcohol to render it hydrophilic. This versatile microfluidic device prototyping technique will be a powerful aid for biological and bio-medical research in both academic and industrial contexts

Size and conformation limits to secretion of disulfide-bonded loops in autotransporter proteins

Autotransporters are a superfamily of virulence factors typified by a channel-forming C terminus that facilitates translocation of the functional N-terminal passenger domain across the outer membrane of Gram-negative bacteria. This final step in the secretion of autotransporters requires a translocation-competent conformation for the passenger domain that differs markedly from the structure of the fully folded secreted protein. The nature of the translocation-competent conformation remains controversial, in particular whether the passenger domain can adopt secondary structural motifs, such as disulfide- bonded segments, while maintaining a secretion-competent state. Here, we used the endogenous and closely spaced cysteine residues of the plasmid-encoded toxin (Pet) from enteroaggregative Escherichia coli to investigate the effect of disulfide bond-induced folding on translocation of an auto-transporter passenger domain. We reveal that rigid structural elements within disulfide-bonded segments are resistant to autotransporter-mediated secretion. We define the size limit of disulfide-bonded segments tolerated by the autotransporter system demonstrating that, when present, cysteine pairs are intrinsically closely spaced to prevent congestion of the translocator pore by large disulfide-bonded regions. These latter data strongly support the hairpin mode of autotransporter biogenesis

Shank3 mutant mice display autistic-like behaviours and striatal dysfunction

Autism spectrum disorders (ASDs) comprise a range of disorders that share a core of neurobehavioural deficits characterized by widespread abnormalities in social interactions, deficits in communication as well as restricted interests and repetitive behaviours. The neurological basis and circuitry mechanisms underlying these abnormal behaviours are poorly understood. SHANK3 is a postsynaptic protein, whose disruption at the genetic level is thought to be responsible for the development of 22q13 deletion syndrome (Phelan–McDermid syndrome) and other non-syndromic ASDs. Here we show that mice with Shank3 gene deletions exhibit self-injurious repetitive grooming and deficits in social interaction. Cellular, electrophysiological and biochemical analyses uncovered defects at striatal synapses and cortico-striatal circuits in Shank3 mutant mice. Our findings demonstrate a critical role for SHANK3 in the normal development of neuronal connectivity and establish causality between a disruption in the Shank3 gene and the genesis of autistic-like behaviours in mice.National Institute of Mental Health (U.S.) (NIMH/NIH (R01MH081201))Hartwell Foundation (Hartwell Individual Biomedical Research Award)Simons Foundation (Autism Research Initiative (SFARI) grant Award)Brain and Behavior Research Foundation (NARSAD Young Investigator Award)National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award (F32MH084460))National Institutes of Health (U.S.) (NIH grant (R03MH085224))Fundação para a Ciência e a Tecnologia (SFRH/BD/15231/2004)Fundação para a Ciência e a Tecnologia (SFRH/BD/15855/2005)Instituto Gulbenkian de Ciência (“Programa Gulbenkian de Doutoramento em Biomedicina” (PGDB, Oeiras, Portugal))University of Coimbra. Center for Neuroscience and Cell Biology (“Programa Doutoral em Biologia Experimental e Biomedicina” (CNC, Coimbra, Portugal)

Adsorption of formate species on Cu(h,k,l) low index surfaces

We report a density functional theory study on the relative stability of formate species on Cu(h,k,l) low index surfaces using a range of exchange-correlation functionals. We find that these functionals predict similar geometries for the formate molecule adsorbed on the Cu surface. A comparison of the calculated vibrational transition energies of a perpendicular configuration of formate on Cu surface shows an excellent agreement with the experimental spectrum obtained from inelastic neutron spectroscopy. From the calculations on adsorption energy we find that formate is most stable on the Cu(110) surface as compared to Cu(111) and Cu(100) surfaces. Bader analysis shows that this feature could be related to the higher charge transfer from the Cu(110) surface and optimum charge density at the interfacial region due to bidirectional electron transfer between the formate and the Cu surface. Analysis of the partial density of states finds that in the –5.5 eV to –4.0 eV region, hybridization between O p and the non-axial Cu dyz and dxz orbitals takes place on the Cu(110) surface, which is energetically more favourable than on the other surfaces