Empowering Control of Antiferromagnets by THz-Induced Spin Coherence.

Finding efficient and ultrafast ways to control antiferromagnets is believed to be instrumental in unlocking their potential for magnetic devices operating at THz frequencies. Still, it is challenged by the absence of net magnetization in the ground state. Here, we show that the magnetization emerging from a state of coherent spin precession in antiferromagnetic iron borate FeBO_{3} can be used to enable the nonlinear coupling of light to another, otherwise weakly susceptible, mode of spin precession. This nonlinear mechanism can facilitate conceptually new ways of controlling antiferromagnetism.

Two-Dimensional Terahertz Spectroscopy of Nonlinear Phononics in the Topological Insulator MnBi_{2}Te_{4}.

The interaction of a single-cycle terahertz electric field with the topological insulator MnBi_{2}Te_{4} triggers strongly anharmonic lattice dynamics, promoting fully coherent energy transfer between the otherwise noninteracting Raman-active E_{g} and infrared (IR)-active E_{u} phononic modes. Two-dimensional terahertz spectroscopy combined with modeling based on the classical equations of motion and symmetry analysis reveals the multistage process underlying the excitation of the Raman-active E_{g} phonon. In this nonlinear combined photophononic process, the terahertz electric field first prepares a coherent IR-active E_{u} phononic state and subsequently interacts with this state to efficiently excite the E_{g} phonon.

Ultrafast kinetics of the antiferromagnetic-ferromagnetic phase transition in FeRh.

Understanding how fast short-range interactions build up long-range order is one of the most intriguing topics in condensed matter physics. FeRh is a test specimen for studying this problem in magnetism, where the microscopic spin-spin exchange interaction is ultimately responsible for either ferro- or antiferromagnetic macroscopic order. Femtosecond laser excitation can induce ferromagnetism in antiferromagnetic FeRh, but the mechanism and dynamics of this transition are topics of intense debates. Employing double-pump THz emission spectroscopy has enabled us to dramatically increase the temporal detection window of THz emission probes of transient states without sacrificing any loss of resolution or sensitivity. It allows us to study the kinetics of emergent ferromagnetism from the femtosecond up to the nanosecond timescales in FeRh/Pt bilayers. Our results strongly suggest a latency period between the initial pump-excitation and the emission of THz radiation by ferromagnetic nuclei.

THz-Scale Field-Induced Spin Dynamics in Ferrimagnetic Iron Garnets.

THz magnetization dynamics of antiferromagnetically coupled spins in ferrimagnetic Tm_{3}Fe_{5}O_{12} is excited by a picosecond single-cycle pulse of a magnetic field and probed with the help of the magneto-optical Faraday effect. Data analysis combined with numerical modeling shows that the dynamics corresponds to the exchange mode excited by the Zeeman interaction of the THz magnetic field with the spins. We argue that THz-pump-IR-probe experiments on ferrimagnets offer a unique tool for quantitative studies of dynamics and mechanisms to control antiferromagnetically coupled spins.

Hypoxia-induced developmental plasticity of the gills and air-breathing organ of Trichopodus trichopterus.

The air-breathing blue gourami Trichopodus trichopterus, an anabantid with a suprabranchial labyrinth organ, was used to study morphological development of respiratory systems in response to chronic hypoxia (13% O2, combined aquatic and aerial hypoxia). Overall growth (fork length, wet mass and cutaneous surface area) of T. trichopterus did not differ between control fish and those reared in hypoxia. Both lamellar and labyrinth surface areas of the hypoxic larvae, however, increased more rapidly than controls, producing c. 16% larger lamellar and 30% larger labyrinth mass-specific surface areas within the first 120 days of development. This is the first study to show developmental respiratory plasticity of a bimodally respiring fish. It reveals that chronic hypoxia stimulates development of the gills and air-breathing organ, and that labyrinth growth is even more sensitive to hypoxia than branchial growth.

First analysis of human herpesvirus 6T-cell responses: specific boosting after HHV6 reactivation in stem cell transplantation recipients.

Early human herpesvirus 6 (HHV6) reactivation after hematopoietic stem cell transplantation (HSCT) is associated with poor survival. We characterized HHV6 immuneresponses in HSCT patients during lymphopenia. Prospectively, HHV6 DNA-load was measured weekly by realtime-PCR. Numbers of IFNγ-producing HHV6-T-cells were retrospectively determined by enzyme-linked immunospot assay 2 months after HSCT. HHV6-specific T-cell proliferative capacity was analyzed with a newly developed assay using antigen-presenting autologous HHV6-infected PBMC. Fifty-six patients were included (median age 4.6 years; range 0.2-21.2 years). HHV6-reactivation occurred in 29/56 (52%) patients with a median time of 14 (range 1-41) days after HSCT. The median number of IFN-γ producing HHV6-specific T-cells at 2 months and the HHV6-specific CD8+ T-cell proliferative capacity at 6 months after HSCT was increased after HHV6-reactivation compared to non-reactivating patients (P=0.006 and p=0.019). In conclusion, HHV6-specific immuneresponses can be initiated during lymphopenia early after HSCT, which implicates a potential window for development of HHV6-specific (immuno)therapy.

Region specific gene expression profile in mouse brain after chronic corticotropin releasing factor receptor 1 activation: the novel role for diazepam binding inhibitor in contextual fear conditioning.

We have previously reported that repeated central administration of sub-anxiogenic doses of the corticotropin releasing factor 1 (CRF(1)) agonist Cortagine, termed "priming," elicits a phenotype of increased anxiety-like behaviors in the elevated plus maze (EPM) and open-field test, and enhanced retention of contextual conditioned fear in C57BL/6J mice. Observed behavioral changes were functionally coupled to CRF(1)-mediated elevated central cholecystokinin (CCK) tone in discrete brain regions. However, the changes in gene expression that mediated "priming"-induced behavioral and concurrent molecular changes in specific brain regions remained unknown. In the present study, a complementary DNA microarray analysis was used to investigate gene expression profiles in the hippocampus and prefrontal cortex (PFC) of C57BL/6J mice following the "priming" procedure. Here, we report that chronic stimulation of CRF(1), by i.c.v. administration of 10 ng Cortagine for five days, brought about alterations in the expression of a wide range of hippocampal (31 genes) and PFC (18 genes) genes, implicated in anxiety and aversive memory formation. These expression changes involved genes associated with signal transduction, neurotransmitter secretion, synaptic transmission, myelination, and others involved in the transport, biosynthesis, and binding of proteins. In particular, several genes of the protein kinase A (PKA) and protein kinase C (PKC) signaling cascades, known to be involved in synaptic plasticity, such as neurogranin, calmodulin 3, and the PKA regulatory subunit 1 b were found to be upregulated in the PFC and hippocampus of CRF(1) agonist "primed" mice. Moreover, we show pharmacologically that one of the newly implicated memory regulatory elements, diazepam-binding inhibitor (DBI) is functionally involved in hippocampus-dependent enhancement of contextual fear, a cardinal phenotypic feature of the "primed" mice. Finally, an interaction network mapping of the altered genes and their known interacting partners identified additional molecular candidates responsible for CRF(1)-mediated hypersensitive fear circuitry.

Genetic evidence for sites of interaction between the Gal3 and Gal80 proteins of the Saccharomyces cerevisiae GAL gene switch.

Galactose-activated transcription of the Saccharomyces cerevisiae GAL genes occurs when Gal3 binds the Gal4 inhibitor, Gal80. Noninteracting variants of Gal3 or Gal80 render the GAL genes noninducible. To identify the binding determinants for Gal3's interaction with Gal80 we carried out GAL3-GAL80 intergenic suppression analyses and selected for new GAL3 mutations that impair the Gal3-Gal80 interaction. We show that a GAL3(C)-D368V mutation can suppress the noninducibility due to a GAL80(S-1)-G323R mutation, and a GAL80-M350C mutation can suppress the noninducibility due to a gal3-D111C mutation. A reverse two-hybrid selection for GAL3 mutations that impair the Gal3-Gal80 interaction yielded 12 single-amino-acid substitutions at residues that are predicted to be surface exposed on Gal3. The majority of the affected Gal3 residues localized to a composite surface that includes D111 and a sequence motif containing D368, which has been implicated in interaction with Gal80. The striking colocalization of intergenic suppressor residues and Gal80 nonbinder residues identifies a Gal3 surface that likely interacts with Gal80.

Treatment strategies of age-related memory dysfunction by modulation of neuronal plasticity.

One of the most remarkable features of the mammalian central nervous system is its ability to store large amounts of information for periods approaching a lifetime. However, during the aging process cognitive domains, such as long-term (declarative) memory and working memory decline in some, but by far not all individuals. It is essential to understand the physiological changes that cause memory decline and also to elucidate why preserved memory abilities vary so greatly across individuals and memory tasks. A generally accepted hypothesis has been that long-lasting activity-dependent changes in the efficacy of synaptic transmission in the mammalian brain are considered to be of fundamental importance for the storage of information. There is now a more detailed understanding of the changes in neuronal plasticity during aging at the molecular and systems levels. This review discusses recent findings on age-related changes in neuronal plasticity, which have opened up novel sites of action for therapeutic intervention.

Molecular evolution of typical enteropathogenic Escherichia coli: clonal analysis by multilocus sequence typing and virulence gene allelic profiling.

Enteropathogenic Escherichia coli (EPEC) infections are a leading cause of infantile diarrhea in developing nations. Typical EPEC isolates are differentiated from other types of pathogenic E. coli by two distinctive phenotypes, attaching effacement and localized adherence. The genes specifying these phenotypes are found on the locus of enterocyte effacement (LEE) and the EPEC adherence factor (EAF) plasmid. To describe how typical EPEC has evolved, we characterized a diverse collection of strains by multilocus sequence typing (MLST) and performed restriction fragment length polymorphism (RFLP) analysis of three virulence genes (eae, bfpA, and perA) to assess allelic variation. Among 129 strains representing 20 O-serogroups, 21 clonal genotypes were identified using MLST. RFLP analysis resolved nine eae, nine bfpA, and four perA alleles. Each bfpA allele was associated with only one perA allele class, suggesting that recombination has not played a large role in shuffling the bfpA and perA loci between separate EAF plasmids. The distribution of eae alleles among typical EPEC strains is more concordant with the clonal relationships than the distribution of the EAF plasmid types. These results provide further support for the hypothesis that the EPEC pathotype has evolved multiple times within E. coli through separate acquisitions of the LEE island and EAF plasmid.

Anthrax vaccines: Pasteur to the present.

Anthrax has been a major cause of death in grazing animals and an occasional cause of death in humans for thousands of years. Since the late 1800s there has been an exceptional international history of anthrax vaccine development. Due to animal vaccinations, the rate of infection has dropped dramatically. Anthrax vaccines have progressed from uncharacterized whole-cell vaccines in 1881, to pXO2-negative spores in the 1930s, to culture filtrates absorbed to aluminum hydroxide in 1970, and likely to recombinant protective antigen in the near future. Each of these refinements has increased safety without significant loss of efficacy. The threat of genetically engineered, antibiotic and vaccine resistant strains of Bacillus anthracis is fueling hypothesis-driven research and global techniques--including genomics, proteomics and transposon site hybridization--to facilitate the discovery of novel vaccine targets. This review highlights historical achievements and new developments in anthrax vaccine research.

Stress-induced alternative splicing of acetylcholinesterase results in enhanced fear memory and long-term potentiation.

Stress insults intensify fear memory; however, the mechanism(s) facilitating this physiological response is still unclear. Here, we report the molecular, neurophysiological and behavioral findings attributing much of this effect to alternative splicing of the acetylcholinesterase (AChE) gene in hippocampal neurons. As a case study, we explored immobilization-stressed mice with intensified fear memory and enhanced long-term potentiation (LTP), in which alternative splicing was found to induce overproduction of neuronal 'readthrough' AChE-R (AChE-R). Selective downregulation of AChE-R mRNA and protein by antisense oligonucleotides abolished the stress-associated increase in AChE-R, the elevation of contextual fear and LTP in the hippocampal CA1 region. Reciprocally, we intrahippocampally injected a synthetic peptide representing the C-terminal sequence unique to AChE-R. The injected peptide, which has been earlier found to exhibit no enzymatic activity, was incorporated into cortical, hippocampal and basal nuclei neurons by endocytosis and retrograde transport and enhanced contextual fear. Compatible with this hypothesis, inherited AChE-R overexpression in transgenic mice resulted in perikaryal clusters enriched with PKCbetaII, accompanied by PKC-augmented LTP enhancement. Our findings demonstrate a primary role for stress-induced alternative splicing of the AChE gene to elevated contextual fear and synaptic plasticity, and attribute to the AChE-R splice variant a major role in this process.

Enteropathogenic Escherichia coli O157 strains from Brazil.

We describe two serogroup O157 Escherichia coli strains from Brazilian infants with diarrhea. A variety of assays indicate that these strains belong to the enteropathogenic, not the enterohemorrhagic, pathotype. These strains possess a novel bfpA allele encoding the type IV pilin characteristic of typical enteropathogenic E. coli strains. Our results emphasize the pitfalls of classifying pathogenic E. coli by serogroup.

Pharmacology and biology of corticotropin-releasing factor (CRF) receptors.

The biology of corticotropin-releasing factor (CRF) finds increasing interest in the scientific community because of the neuromodulatory actions of CRF on brain functions such as learning, anxiety, feeding, and locomotion. Additional actions on immunumodulation and apoptosis have recently been discovered. All actions of CRF are mediated by G protein-coupled receptors, which trigger different, sometimes opposite actions in different regions of the central nervous system. The CRF system exhibits considerable plasticity by the involvement of numerous different ligands, splice variants, and transductional couplings. The generation of multiple splice variants is facilitated by the intron exon structure of the CRF receptor genes.

[Ga18(SitBu3)8] and [Ga22(SitBu3)8]--syntheses and structural characterization of novel gallium cluster compounds.

The novel neutral gallium cluster compounds [Ga18R*8] (1) and [Ga22R*8] (2) are obtained by warming up a metastable solution of gallium(I) bromide in THF/C6H5CH3 after addition of equimolar amounts of supersilyl sodium NaR* from -78 degrees C to room temperature (R* = SitBu3 = supersilyl). From X-ray structure analyses, the observed arrangements of the 18 and 22 Ga atoms in 1 and 2, respectively, are comparable with an 18 atom section of the beta-Ga modification, or show at least some kind of relationship to a 22 atom section of the Ga-III modification. This allows a description of both the clusters as metalloid. The topology of the atoms in 2 is also well explained by the Wade-Mingos rules as an eightfold capped closo-Ga14 cluster, whereby the Ga atoms of Ga14 occupy the center and the corners of a cuboctahedron with one Ga3 face replaced by a Ga4 face. Some concepts are presented about the formation mechanism, the cluster growth, and the metalloid character of the two Ga cluster compounds.

HMG-D and histone H1 interplay during chromatin assembly and early embryogenesis.

HMG-D is an abundant chromosomal protein associated with condensed chromatin during the first nuclear cleavage cycles of the developing Drosophila embryo. We previously suggested that HMG-D might substitute for the linker histone H1 in the preblastoderm embryo and that this substitution might result in the characteristic less compacted chromatin. We have now studied the association of HMG-D with chromatin using a cell-free system for chromatin reconstitution derived from Drosophila embryos. Association of HMG-D with chromatin, like that of histone H1, increases the nucleosome spacing indicative of binding to the linker DNA between nucleosomes. HMG-D interacts with DNA during the early phases of nucleosome assembly but is gradually displaced as chromatin matures. By contrast, purified chromatin can be loaded with stoichiometric amounts of HMG-D, and this can be displaced upon addition of histone H1. A direct physical interaction between HMG-D and histone H1 was observed in a Far Western analysis. The competitive nature of this interaction is reminiscent of the apparent replacement of HMG-D by H1 during mid-blastula transition. These data are consistent with the hypothesis that HMG-D functions as a specialized linker protein prior to appearance of histone H1.

Novel topology of BfpE, a cytoplasmic membrane protein required for type IV fimbrial biogenesis in enteropathogenic Escherichia coli.

Enteropathogenic Escherichia coli (EPEC) produces the bundle-forming pilus (BFP), a type IV fimbria that has been implicated in virulence, autoaggregation, and localized adherence to epithelial cells. The bfpE gene is one of a cluster of bfp genes previously shown to encode functions that direct BFP biosynthesis. Here, we show that an EPEC strain carrying a nonpolar mutation in bfpE fails to autoaggregate, adhere to HEp-2 cells, or form BFP, thereby demonstrating that BfpE is required for BFP biogenesis. BfpE is a cytoplasmic membrane protein of the GspF family. To determine the membrane topology of BfpE, we fused bfpE derivatives containing 3' truncations and/or internal deletions to alkaline phosphatase and/or beta-galactosidase reporter genes, whose products are active only when localized to the periplasm or cytoplasm, respectively. In addition, we constructed BfpE sandwich fusions using a dual alkaline phosphatase/beta-galactosidase reporter cassette and analyzed BfpE deletion derivatives by sucrose density flotation gradient fractionation. The data from these analyses support a topology in which BfpE contains four hydrophobic transmembrane (TM) segments, a large cytoplasmic segment at its N terminus, and a large periplasmic segment near its C terminus. This topology is dramatically different from that of OutF, another member of the GspF family, which has three TM segments and is predominantly cytoplasmic. These findings provide a structural basis for predicting protein-protein interactions required for assembly of the BFP biogenesis machinery.

Molecular variation among type IV pilin (bfpA) genes from diverse enteropathogenic Escherichia coli strains.

Typical enteropathogenic Escherichia coli (EPEC) strains produce bundle-forming pili (BFP), type IVB fimbriae that have been implicated in EPEC virulence, antigenicity, autoaggregation, and localized adherence to epithelial cells (LA). BFP are polymers of bundlin, a pilin protein that is encoded by the bfpA gene found on a large EPEC plasmid. Striking sequence variation has previously been observed among type IV pilin genes of other gram-negative bacterial pathogens (e.g., Pseudomonas and Neisseria spp.). In contrast, the established sequences of bfpA genes from two distantly related prototype EPEC strains vary by only a single base pair. To determine whether bundlin sequences vary more extensively, we used PCR to amplify the bfpA genes from 19 EPEC strains chosen for their various serotypes and sites and years of isolation. Eight different bfpA alleles were identified by sequencing of the PCR products. These alleles can be classified into two major groups. The alpha group contains three alleles derived from strains carrying O55, O86, O111, O119, O127, or O128 somatic antigens. The beta group contains five alleles derived from strains carrying O55, O110, O128ab, O142, or nontypeable antigens. Sequence comparisons show that bundlin has highly conserved and variable regions, with most of the variation occurring in the C-terminal two-thirds of the protein. The results of multilocus enzyme electrophoresis support the hypothesis that bfpA sequences have spread horizontally across distantly related clonal lineages. Strains with divergent bundlin sequences express bundlin protein, produce BFP, and carry out autoaggregation and LA. However, four strains lack most or all of these phenotypes despite having an intact bfpA gene. These results have important implications for our understanding of bundlin structure, transmission of the bfp gene cluster among EPEC strains, and the role of bundlin variation in the evasion of host immune system responses.

Modulation of hypothalamic NMDA receptor function by cyclic AMP-dependent protein kinase and phosphatases.

In the present study we investigated the modulation of hypothalamic NMDA receptor-mediated currents by cyclic AMP-dependent protein kinase (PKA) using the two-electrode voltage-clamp technique in Xenopus oocytes injected with rat hypothalamic mRNA. Application of forskolin, which activates PKA by means of cyclic AMP stimulation, caused a transient increase of NMDA-induced currents, whereas the inactive forskolin analogue 1,9-dideoxyforskolin had no effect. Incubation of oocytes with a membrane-permeable analogue of cyclic AMP, 8-bromoadenosine 3',5' -cyclic monophosphate, potentiated NMDA responses even more prominently than with forskolin. NMDA-induced currents recorded from Xenopus oocytes injected with cRNA encoding the NMDA receptor subunits NR1, NR2A, and/or NR2B, mainly found in rat hypothalamus, were not affected by PKA activation but were increased by protein kinase C (PKC) stimulation. It is interesting that inhibition of endogenous protein phosphatase 1 and/or 2A by calyculin A resulted in a similar enhancement of hypothalamic NMDA-induced currents. Preinjection of oocytes with calyculin A impeded the PKA- but not the PKC-mediated potentiation of hypothalamic NMDA-induced currents. We propose the involvement of an additional third messenger in the PKA effect, which acts most likely via the inhibition of tonically active protein phosphatase 1 and/or 2A.

In vivo NMDA/dopamine interaction resulting in Fos production in the limbic system and basal ganglia of the mouse brain.

Glutamatergic and dopaminergic effects on molecular processes have been extensively investigated in the basal ganglia. It has been demonstrated that NMDA and dopamine D(1) and D(2) receptors interact in the regulation of signal transduction and induction of transcription factors. In the present experiments, NMDA/dopamine interactions were investigated in the normosensitive caudate nucleus, hippocampus and amygdala by monitoring Fos production. We demonstrated that NMDA and the D(1) receptor agonist SKF 38393 triggered Fos levels in a distinct, non-overlapping and region-specific pattern. NMDA injected intraperitoneally (i.p.) elevated Fos levels in all hippocampal subfields and the central amygdala, whereas SKF 38393 triggered Fos production in basomedial, cortical, medial amygdala and caudate nucleus. The NMDA receptor antagonist CGS 19755 prevented NMDA- and SKF 38393-triggered Fos production in all investigated brain areas. Similarly, the D(1) receptor antagonist SCH 23390 inhibited the effects produced by SKF 38393 or NMDA. The D(2) receptor antagonist sulpiride exerted synergistic and antagonistic effects on NMDA- and SKF 38393-triggered Fos production, in a region specific manner. These data suggest that NMDA and dopamine receptors regulate Fos production within the limbic system and basal ganglia through regionally differentiated but interdependent actions.