Tet1 Isoforms Differentially Regulate Gene Expression, Synaptic Transmission, and Memory in the Mammalian Brain.

The dynamic regulation of DNA methylation in postmitotic neurons is necessary for memory formation and other adaptive behaviors. Ten-eleven translocation 1 (TET1) plays a part in these processes by oxidizing 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), thereby initiating active DNA demethylation. However, attempts to pinpoint its exact role in the nervous system have been hindered by contradictory findings, perhaps due in part, to a recent discovery that two isoforms of the Tet1 gene are differentially expressed from early development into adulthood. Here, we demonstrate that both the shorter transcript (Tet1S ) encoding an N-terminally truncated TET1 protein and a full-length Tet1 (Tet1FL ) transcript encoding canonical TET1 are co-expressed in the adult mouse brain. We show that Tet1S is the predominantly expressed isoform and is highly enriched in neurons, whereas Tet1FL is generally expressed at lower levels and more abundant in glia, suggesting their roles are at least partially cell type-specific. Using viral-mediated, isoform and neuron-specific molecular tools, we find that the individual repression of each transcript leads to the dysregulation of unique gene ensembles and contrasting changes in basal synaptic transmission. In addition, Tet1S repression enhances, while Tet1FL impairs, hippocampal-dependent memory in male mice. Together, our findings demonstrate that each Tet1 isoform serves a distinct role in the mammalian brain.SIGNIFICANCE STATEMENT In the brain, activity-dependent changes in gene expression are required for the formation of long-term memories. DNA methylation plays an essential role in orchestrating these learning-induced transcriptional programs by influencing chromatin accessibility and transcription factor binding. Once thought of as a stable epigenetic mark, DNA methylation is now known to be impermanent and dynamically regulated, driving neuroplasticity in the brain. We found that Tet1, a member of the ten-eleven translocation (TET) family of enzymes that mediates removal of DNA methyl marks, is expressed as two separate isoforms in the adult mouse brain and that each differentially regulates gene expression, synaptic transmission and memory formation. Together, our findings demonstrate that each Tet1 isoform serves a distinct role in the CNS.

First record of second-generation facultative parthenogenesis in a vertebrate species, the whitespotted bambooshark Chiloscyllium plagiosum.

In this study, two parthenogenetic events within a family of the whitespotted bambooshark Chiloscyllium plagiosum are reported. A captive female produced multiple parthenogens. Unexpectedly, a single specimen of a total of nine parthenogens displayed external claspers characterizing the male sex in chondrichthyans. Upon dissection, internal sexual organs of this specimen were malformed or absent; however, the presence of claspers in this study challenges the as yet assumed sex determination system in this shark species. Even more remarkable was that one of the female parthenogens reproduced asexually again producing viable offspring. As far as is known, this is the first genetically confirmed evidence for second-generation facultative parthenogenesis in vertebrates. These results support the evolutionary significance of parthenogenesis as an alternative to sexual reproduction.

Development of very high Jc in Ba(Fe1-xCox)2As2 thin films grown on CaF2.

Ba(Fe(1-x)Co(x))(2)As(2) is the most tunable of the Fe-based superconductors (FBS) in terms of acceptance of high densities of self-assembled and artificially introduced pinning centres which are effective in significantly increasing the critical current density, J(c). Moreover, FBS are very sensitive to strain, which induces an important enhancement in critical temperature, T(c), of the material. In this paper we demonstrate that strain induced by the substrate can further improve J(c) of both single and multilayer films by more than that expected simply due to the increase in T(c). The multilayer deposition of Ba(Fe(1-x)Co(x))(2)As(2) on CaF2 increases the pinning force density (F(p) = J(c) × µ0H) by more than 60% compared to a single layer film, reaching a maximum of 84 GN/m(3) at 22.5 T and 4.2 K, the highest value ever reported in any 122 phase.

Artificially engineered superlattices of pnictide superconductors.

Significant progress has been achieved in fabricating high-quality bulk and thin-film iron-based superconductors. In particular, artificial layered pnictide superlattices offer the possibility of tailoring the superconducting properties and understanding the mechanism of the superconductivity itself. For high-field applications, large critical current densities (J(c)) and irreversibility fields (H(irr)) are indispensable along all crystal directions. On the other hand, the development of superconducting devices such as tunnel junctions requires multilayered heterostructures. Here we show that artificially engineered undoped Ba-122/Co-doped Ba-122 compositionally modulated superlattices produce ab-aligned nanoparticle arrays. These layer and self-assemble along c-axis-aligned defects, and combine to produce very large J(c) and H(irr) enhancements over a wide angular range. We also demonstrate a structurally modulated SrTiO3(STO)/Co-doped Ba-122 superlattice with sharp interfaces. Success in superlattice fabrication involving pnictides will aid the progress of heterostructured systems exhibiting new interfacial phenomena and device applications.

High intergrain critical current density in fine-grain (Ba0.6K0.4)Fe2As2 wires and bulks.

The K- and Co-doped BaFe(2)As(2) (Ba-122) superconducting compounds are potentially useful for applications because they have upper critical fields (H(c2)) of well over 50 T, H(c2) anisotropy γ < 2and thin-film critical current densities J(c) exceeding 1 MA cm(-2) (refs 1-4) at 4.2 K. However, thin-film bicrystals of Co-doped Ba-122 clearly exhibit weak link behaviour for [001] tilt misorientations of more than about 5°, suggesting that textured substrates would be needed for applications, as in the cuprates. Here we present a contrary and very much more positive result in which untextured polycrystalline (Ba(0.6)K(0.4))Fe(2)As(2) bulks and round wires with high grain boundary density have transport critical current densities well over 0.1 MA cm(-2) (self-field, 4.2 K), more than 10 times higher than that of any other round untextured ferropnictide wire and 4-5 times higher than the best textured flat wire. The enhanced grain connectivity is ascribed to their much improved phase purity and to the enhanced vortex stiffness of this low-anisotropy compound (γ~1-2) when compared with YBa(2)Cu(3)O(7-x) (γ~5).

Template engineering of Co-doped BaFe2As2 single-crystal thin films.

Understanding new superconductors requires high-quality epitaxial thin films to explore intrinsic electromagnetic properties and evaluate device applications. So far, superconducting properties of ferropnictide thin films seem compromised by imperfect epitaxial growth and poor connectivity of the superconducting phase. Here we report new template engineering using single-crystal intermediate layers of (001) SrTiO(3) and BaTiO(3) grown on various perovskite substrates that enables genuine epitaxial films of Co-doped BaFe(2)As(2) with a high transition temperature (T(c,rho=0) of 21.5 K, where rho=resistivity), a small transition width (DeltaT(c)=1.3 K), a superior critical current density J(c) of 4.5 MA cm(-2) (4.2 K) and strong c-axis flux pinning. Implementing SrTiO(3) or BaTiO(3) templates to match the alkaline-earth layer in the Ba-122 with the alkaline-earth/oxygen layer in the templates opens new avenues for epitaxial growth of ferropnictides on multifunctional single-crystal substrates. Beyond superconductors, it provides a framework for growing heteroepitaxial intermetallic compounds on various substrates by matching interfacial layers between templates and thin-film overlayers.

Phase-incoherent superconducting pairs in the normal state of Ba(Fe(1-x)Co(x))2As2.

The normal state properties of the recently discovered ferropnictide superconductors might hold the key to understanding their exotic superconductivity. Using point-contact spectroscopy we show that Andreev reflection between an epitaxial thin film of Ba(Fe(0.92)Co(0.08))2As2 and a silver tip can be seen in the normal state of the film up to temperature T∼1.3T(c), where T(c) is the critical temperature of the superconductor. Andreev reflection far above T(c) can be understood only when superconducting pairs arising from strong fluctuation of the phase of the complex superconducting order parameter exist in the normal state. Our results provide spectroscopic evidence of phase-incoherent superconducting pairs in the normal state of the ferropnictide superconductors.

Multigap superconductivity and strong electron-boson coupling in Fe-based superconductors: a point-contact Andreev-reflection study of Ba(Fe(1-x)Co(x))2As2 single crystals.

Directional point-contact Andreev-reflection measurements in Ba(Fe(1-x)Co(x))2As2 single crystals (T(c) = 24.5 K) indicate the presence of two superconducting gaps with no line nodes on the Fermi surface. The point-contact Andreev-reflection spectra also feature additional structures related to the electron-boson interaction, from which the characteristic boson energy Ω(b)(T) is obtained, very similar to the spin-resonance energy observed in neutron scattering experiments. Both the gaps and the additional structures can be reproduced within a three-band s ± Eliashberg model by using an electron-boson spectral function peaked at Ω(0) = 12 meV ≃ Ω(b)(0).

A prospective, double-blind, randomized, controlled clinical trial of ampicillin-sulbactam for preterm premature rupture of membranes in women receiving antenatal corticosteroid therapy.

OBJECTIVE: Our purpose was to test the efficacy of antibiotic prophylaxis in women with preterm premature rupture of the membranes who receive antenatal corticosteroids. STUDY DESIGN: A total of 112 women received one of three regimens in a double-blind randomized controlled trial: (1) ampicillin-sulbactam for 72 hours followed by amoxicillin-clavulanate, (2) ampicillin for 72 hours followed by amoxicillin, or (3) placebo. RESULTS: A total of 48.6% of neonates in the placebo group either died or had sepsis or respiratory distress syndrome versus 29.3% in the pooled antibiotic group (p < 0.05) and 26.3% in the ampicillin-sulbactam/amoxicillin-clavulanate subgroup (p < 0.05). All three neonatal deaths occurred in the placebo group (p = 0.03 versus pooled antibiotics). Mean birth weight was significantly greater in the pooled antibiotic group (1773 gm, p = 0.04) and in the ampicillin-sulbactam/amoxicillin-clavulanate subgroup (1870 gm, p = 0.02) than in the placebo group (1543 gm). Antibiotic prophylaxis reduced the need for prolonged ventilation (p = 0.05). CONCLUSIONS: Antibiotic prophylaxis in combination with corticosteroids in preterm premature rupture of membranes significantly lowered the total frequency of neonatal mortality, sepsis, and respiratory distress syndrome and significantly increased birth weight compared with corticosteroids alone.

Frequency response of the atmosphere under thermal blooming conditions.

An analysis, using a single-phase-sheet model, of the effect of an oscillating thermally bloomed atmosphere on a high-power laser beam is presented. The oscillations are caused by a small modulation of the wave front of the beam at the transmitter. The primary contention made here is that the time-dependent blooming is not an oscillating version of its static counterpart; rather, new gratinglike effects are introduced by the interaction of the crosswind and the dithered high-power beam. The resulting temporal variations of the target-plane irradiance at the position of its static bloomed peak are examined and implications for slow dither are discussed.

Thermal blooming: round beam vs square beam.

We have examined Fried's suggestion that an initially square high-power laser beam will experience significantly less thermal blooming than a round beam. In almost every case of interest the computer results were the opposite of what he suggested, indicating the importance, and rather unintuitive nature, of diffraction.