Motor training promotes both synaptic and intrinsic plasticity of layer V pyramidal neurons in the primary motor cortex.

Layer V neurons in the primary motor cortex (M1) are important for motor skill learning. Since pretreatment of either CNQX or APV in rat M1 layer V impaired rotor rod learning, we analysed training-induced synaptic plasticity by whole-cell patch-clamp technique in acute brain slices. Rats trained for 1 day showed a decrease in small inhibitory postsynaptic current (mIPSC) frequency and an increase in the paired-pulse ratio of evoked IPSCs, suggesting a transient decrease in presynaptic GABA release in the early phase. Rats trained for 2 days showed an increase in miniature excitatory postsynaptic current (mEPSC) amplitudes/frequency and elevated AMPA/NMDA ratios, suggesting a long-term strengthening of AMPA receptor-mediated excitatory synapses. Importantly, rotor rod performance in trained rats was correlated with the mean mEPSC amplitude and the frequency obtained from that animal. In current-clamp analysis, 1-day-trained rats transiently decreased the current-induced firing rate, while 2-day-trained rats returned to pre-training levels, suggesting dynamic changes in intrinsic properties. Furthermore, western blot analysis of layer V detected decreased phosphorylation of Ser408-409 in GABAA receptor ß3 subunits in 1-day-trained rats, and increased phosphorylation of Ser831 in AMPA receptor GluA1 subunits in 2-day-trained rats. Finally, live-imaging analysis of Thy1-YFP transgenic mice showed that the training rapidly recruited a substantial number of spines for long-term plasticity in M1 layer V neurons. Taken together, these results indicate that motor training induces complex and diverse plasticity in M1 layer V pyramidal neurons. KEY POINTS: Here we examined motor training-induced synaptic and intrinsic plasticity of layer V pyramidal neurons in the primary motor cortex. The training reduced presynaptic GABA release in the early phase, but strengthened AMPA receptor-mediated excitatory synapses in the later phase: acquired motor performance after training correlated with the strength of excitatory synapses rather than inhibitory synapses. As to the intrinsic property, the training transiently decreased the firing rate in the early phase, but returned to pre-training levels in the later phase. Western blot analysis detected decreased phosphorylation of Ser408-409 in GABAA receptor ß3 subunits in the acute phase, and increased phosphorylation of Ser831 in AMPA receptor GluA1 subunits in the later phase. Live-imaging analysis of Thy1-YFP transgenic mice showed rapid and long-term spine plasticity in M1 layer V neurons, suggesting training-induced increases in self-entropy per spine.

Exchange-Driven Spin Relaxation in Ferromagnet-Oxide-Semiconductor Heterostructures.

We demonstrate that electron spin relaxation in GaAs in the proximity of a Fe/MgO layer is dominated by interaction with an exchange-driven hyperfine field at temperatures below 60 K. Temperature-dependent spin-resolved optical pump-probe spectroscopy reveals a strong correlation of the electron spin relaxation with carrier freeze-out, in quantitative agreement with a theoretical interpretation that at low temperatures the free-carrier spin lifetime is dominated by inhomogeneity in the local hyperfine field due to carrier localization. As the regime of large nuclear inhomogeneity is accessible in these heterostructures for magnetic fields <3 kG, inferences from this result resolve a long-standing and contentious dispute concerning the origin of spin relaxation in GaAs at low temperature when a magnetic field is present. Further, this improved fundamental understanding clarifies the importance of future experiments probing the time-dependent exchange interaction at a ferromagnet-semiconductor interface and its consequences for spin dissipation and transport during spin pumping.

Weight change after 20 years of age and the incidence of dyslipidemia: a cohort study of Japanese male workers.

BACKGROUND: While heavier weight is known to increase the incidence of dyslipidemia, limited data are available on the relationship between weight gain and its development. METHODS: A total of 2647 males were categorized into the following four groups according to the difference between their self-reported weight at 20 years of age and their measured weight in 1994-95: a loss of ≥5% (decrease), loss of <5% or gain of <5% (no change), gain of ≥5 to <15% (increase) and gain of ≥15% (sizable increase). They were followed up until their 2002-03 health examination. Using the 'no change' group as reference, the multivariable-adjusted odds ratio (adjusted for age, body mass index at 20 years of age, physical activity, smoking and alcohol intake) and 95% confidence interval (95% CI) for the incidence of dyslipidemia were determined using logistic regression models. RESULTS: A total of 1342 participants developed dyslipidemia during the follow-up period. The 'increase' and 'sizable increase' groups had odds ratios for the incidence of dyslipidemia of 1.97 (95% CI, 1.59-2.45) and 2.68 (2.15-3.34), respectively, demonstrating that there was a significant dose-response association between weight gain since 20 years of age and the incidence of dyslipidemia (P < 0.001 for trend). CONCLUSION: These results suggest that dyslipidemia could be prevented by avoiding weight gain in adulthood.

Ferromagnetic Resonance Spin Pumping and Electrical Spin Injection in Silicon-Based Metal-Oxide-Semiconductor Heterostructures.

We present the measurement of ferromagnetic resonance (FMR-)driven spin pumping and three-terminal electrical spin injection within the same silicon-based device. Both effects manifest in a dc spin accumulation voltage V_{s} that is suppressed as an applied field is rotated to the out-of-plane direction, i.e., the oblique Hanle geometry. Comparison of V_{s} between these two spin injection mechanisms reveals an anomalously strong suppression of FMR-driven spin pumping with increasing out-of-plane field H_{app}^{z}. We propose that the presence of the large ac component to the spin current generated by the spin pumping approach, expected to exceed the dc value by 2 orders of magnitude, is the origin of this discrepancy through its influence on the spin dynamics at the oxide-silicon interface. This convolution, wherein the dynamics of both the injector and the interface play a significant role in the spin accumulation, represents a new regime for spin injection that is not well described by existing models of either FMR-driven spin pumping or electrical spin injection.

Life history and reproductive ecology of the endangered Itasenpara bitterling Acheilognathus longipinnis (Cyprinidae) in the Himi region, central Japan.

The life history, reproductive ecology and habitat utilization of the Itasenpara (deepbody) bitterling Acheilognathus longipinnis were investigated in a lowland segment of the Moo River in Toyama Prefecture, central Honshu, Japan. Analysis of 1285 individuals revealed that the study population comprised a single size class, an age at maturation of 3 months and a life span of 1 year. On the basis of the growth pattern, the life cycle was divided into two stages: the juvenile stage, characterized by rapid growth, and the adult stage at which growth ceased. Spawning by A. longipinnis was recorded between early September and late October. Female A. longipinnis in the 0+ year age class began to mature when they reached a standard length (LS ) of 56·4 mm. Mature females had a large clutch size (maximum 273 eggs) and deposited highly adhesive and relatively large eggs (2·55 mm(3) ; major axis, 3·12 mm; minor axis, 1·22 mm) via a short ovipositor (mean length, 21·5 mm) into freshwater mussels. The embryos remained in the gill cavities of the freshwater mussels (used as a spawning substratum) and emerged as juveniles (LS , 9 mm). Habitat utilization during spawning was analysed using a generalized linear model. The best-fit model showed that three environmental factors (freshwater mussel availability, water depth and vegetation cover) were important variables for habitat utilization by A. longipinnis. Shallow areas (water depth, 250-330 mm) created for rice paddy management and areas with an abundance of cover were particularly effective for predator avoidance. These results suggest that maintenance of water level fluctuations corresponding with rice cultivation and the abundance of vegetation on the river bank (particularly avoidance of concrete revetments) is essential for conservation of this species under current practices for rice cultivation in Japan.

Transmission of Mycobacterium orygis (M. tuberculosis complex species) from a tuberculosis patient to a dairy cow in New Zealand.

Mycobacterium orygis, previously called the oryx bacillus, is a member of the Mycobacterium tuberculosis complex and has been reported only recently as a cause of human tuberculosis in patients of South Asian origin. We present the first case documenting the transmission of this organism from a human to a cow.

Spin relaxation in single-layer and bilayer graphene.

We investigate spin relaxation in graphene spin valves and observe strongly contrasting behavior for single-layer graphene (SLG) and bilayer graphene (BLG). In SLG, the spin lifetime (τ(s)) varies linearly with the momentum scattering time (τ(p)) as carrier concentration is varied, indicating the dominance of Elliot-Yafet (EY) spin relaxation at low temperatures. In BLG, τ(s) and τ(p) exhibit an inverse dependence, which indicates the dominance of Dyakonov-Perel spin relaxation at low temperatures. The different behavior is due to enhanced screening and/or reduced surface sensitivity of BLG, which greatly reduces the impurity-induced EY spin relaxation.

Assessment of live candidate vaccines for paratuberculosis in animal models and macrophages.

Mycobacterium avium subsp. paratuberculosis (basonym M. paratuberculosis) is the causative agent of paratuberculosis, a chronic enteritis of ruminants. To control the considerable economic effect that paratuberculosis has on the livestock industry, a vaccine that induces protection with minimal side effects is required. We employed transposon mutagenesis and allelic exchange to develop three potential vaccine candidates, which were then tested for virulence with macrophages, mice, and goats. All three models identified the WAg906 mutant as being the most attenuated, but some differences in the levels of attenuation were evident among the models when testing the other strains. In a preliminary mouse vaccine experiment, limited protection was induced by WAg915, as evidenced by a reduced bacterial load in spleens and livers 12 weeks following intraperitoneal challenge with M. paratuberculosis K10. While we found macrophages and murine models to be rapid and cost-effective alternatives for the initial screening of M. paratuberculosis mutants for attenuation, it appears necessary to do the definitive assessment of attenuation with a ruminant model.

Tunneling spin injection into single layer graphene.

We achieve tunneling spin injection from Co into single layer graphene (SLG) using TiO2 seeded MgO barriers. A nonlocal magnetoresistance (ΔR(NL)) of 130 Ω is observed at room temperature, which is the largest value observed in any material. Investigating ΔR(NL) vs SLG conductivity from the transparent to the tunneling contact regimes demonstrates the contrasting behaviors predicted by the drift-diffusion theory of spin transport. Furthermore, tunnel barriers reduce the contact-induced spin relaxation and are therefore important for future investigations of spin relaxation in graphene.

Oscillatory spin polarization and magneto-optical Kerr effect in Fe3O4 thin films on GaAs(001).

The spin dependent properties of epitaxial Fe3O4 thin films on GaAs(001) are studied by the ferromagnetic proximity polarization (FPP) effect and magneto-optical Kerr effect (MOKE). Both FPP and MOKE show oscillations with respect to Fe3O4 film thickness, and the oscillations are large enough to induce repeated sign reversals. We attribute the oscillatory behavior to spin-polarized quantum well states forming in the Fe3O4 film. Quantum confinement of the t(2g) states near the Fermi level provides an explanation for the similar thickness dependences of the FPP and MOKE oscillations.

Manipulation of spin transport in graphene by surface chemical doping.

The effects of surface chemical doping on spin transport in graphene are investigated by performing nonlocal measurements in ultrahigh vacuum while depositing gold adsorbates. We demonstrate manipulation of the gate-dependent nonlocal spin signal as a function of gold coverage. We discover that charged impurity scattering is not the dominant mechanism for spin relaxation in graphene, despite its importance for momentum scattering. Finally, unexpected enhancements of the spin lifetime illustrate the complex nature of spin relaxation in graphene.

Negative intrinsic resistivity of an individual domain wall in epitaxial (Ga,Mn)As microdevices.

Magnetic domains, and the boundaries that separate them (domain walls, DWs), play a central role in the science of magnetism. Understanding and controlling domains is important for many technological applications in spintronics, and may lead to new devices. Although theoretical efforts have elucidated several mechanisms underlying the resistance of a single DW, various experiments report conflicting results, even for the overall sign of the DW resistance. The question of whether an individual DW gives rise to an increase or decrease of the resistance therefore remains open. Here we report an approach to DW studies in a class of ferromagnetic semiconductors (as opposed to metals) that offer promise for spintronics. These experiments involve microdevices patterned from monocrystalline (Ga,Mn)As epitaxial layers. The giant planar Hall effect that we previously observed in this material enables direct, real-time observation of the propagation of an individual magnetic DW along multiprobe devices. We apply steady and pulsed magnetic fields, to trap and carefully position an individual DW within each separate device studied. This protocol reproducibly enables high-resolution magnetoresistance measurements across an individual wall. We consistently observe negative intrinsic DW resistance that scales with channel width. This appears to originate from sizeable quantum corrections to the magnetoresistance.

Ferromagnetic imprinting of nuclear spins in semiconductors.

We examine how a ferromagnetic layer affects the coherent electron spin dynamics in a neighboring gallium arsenide semiconductor. Ultrafast optical pump-probe measurements reveal that the spin dynamics are unexpectedly dominated by hyperpolarized nuclear spins that align along the ferromagnet's magnetization. We find evidence that photoexcited carriers acquire spin-polarization from the ferromagnet, and dynamically polarize these nuclear spins. The resulting hyperfine fields are as high as 9000 gauss in small external fields (less than 1000 gauss), enabling ferromagnetic control of local electron spin coherence.

Isolation of Mycobacterium bovis and other mycobacterial species from ferrets and stoats.

As part of wildlife surveillance for bovine tuberculosis, pooled lymph nodes from 21,481 ferrets, 1056 stoats and 83 weasels were cultured for mycobacteria. A total of 268 isolates of Mycobacterium bovis were obtained from ferrets, 2 from stoats and none from weasels, demonstrating the presence of a wildlife reservoir of infection in ferrets. DNA typing by restriction endonuclease analysis (REA) of 48 selected isolates of M. bovis revealed 23 REA types. Twenty-one of these types had previously been isolated from cattle and farmed deer, demonstrating a complex cycle of infection involving wildlife and domestic animals. Apart from M. bovis, a further 208 mycobacterial isolates were obtained, the majority of which (178) were members of the M. avium complex. Speciation of the remaining 30 mycobacterial isolates by DNA sequencing of the 16s rRNA gene, identified half the isolates as M. triplex. Other species identified included M. fortuitum, M. florentinum, M. interjectum, M. intracellulare, M. holsaticum, and M. septicum/M. peregrinum.

Randomized cross-over comparison of cervical-spine motion with the AirWay Scope or Macintosh laryngoscope with in-line stabilization: a video-fluoroscopic study.

BACKGROUND: The AirWay Scope (AWS) is a fibreoptic device that allows for intubation without alignment of the oral, pharyngeal, and tracheal axes. It may be useful for patients with an unstable cervical-spine (C-spine) or when C-spine movement is undesirable. This study was conducted to fluoroscopically evaluate upper C-spine movement during tracheal intubation with the AWS and or the Macintosh laryngoscope with in-line stabilization (ILS). METHODS: Thirteen patients with a normal C-spine and scheduled for elective surgery agreed to simulation of an unstable C-spine and ILS. Two attempts at laryngoscopy were allowed. Laryngoscopy was performed with the Macintosh laryngoscope, then with the AWS, or vice versa. The movement of the upper C-spine during intubation was examined by measuring the angles formed by adjacent vertebrae from the occiput to C4. Time to achievement of intubation was also recorded. RESULTS: The AWS significantly decreased median movement of the C-spine at the occiput/C1, C1/C2, and C3/C4 concentrations (P=0.041, 0.0079, and 0.0050, respectively), resulting in a significant decrease in cumulative upper C-spine movement (13.5 degrees with the AWS compared with 30.5 degrees with the Macintosh laryngoscope, P<0.01). Intubation time did not differ [23.8 (SD 16.7) s with the AWS; 17.9 (6.4) s with the Macintosh]. CONCLUSIONS: In comparison with the use of the Macintosh laryngoscope, the AWS decreased median upper C-spine movement during intubation under ILS in patients with normal C-spine.

Upper cervical spine movement during intubation: fluoroscopic comparison of the AirWay Scope, McCoy laryngoscope, and Macintosh laryngoscope.

BACKGROUND: The AirWay Scope (AWS) is a new fibreoptic intubation device, which allows visualization of the glottic structures without alignment of the oral, pharyngeal, and tracheal axes, and thus may be useful in patients with limited cervical spine (C-spine) movement. We fluoroscopically evaluated upper C-spine movement during intubation with the AWS or Macintosh or McCoy laryngoscope. METHODS: Forty-five patients, with normal C-spine, scheduled for elective surgery were randomly assigned to one of the three intubation devices. Movement of the upper C-spine was examined by measuring angles formed by adjacent vertebrae during intubation. Time to intubation was also recorded. RESULTS: Median cumulative upper C-spine movement was 22.3 degrees, 32.3 degrees, and 36.5 degrees with the AWS, Macintosh laryngoscope, and McCoy laryngoscope, respectively (P<0.001, AWS vs, Macintosh and McCoy). The AWS reduced maximum movement of the C-spine at C1/C2 in comparison with the Macintosh or McCoy laryngoscope (P=0.012), and at C3/C4 in comparison with the McCoy laryngoscope (P=0.019). Intubation time was significantly longer in the AWS group than in the Macintosh group (P=0.03). CONCLUSIONS: Compared with the Macintosh or McCoy laryngoscope, the AWS produced less movement of upper C-spine for intubation in patients with a normal C-spine.

Blockade of the natriuretic peptide receptor guanylyl cyclase-A inhibits NF-kappaB activation and alleviates myocardial ischemia/reperfusion injury.

Acute myocardial infarction (AMI) remains the leading cause of death in developed countries. Although reperfusion of coronary arteries reduces mortality, it is associated with tissue injury. Endothelial P-selectin-mediated infiltration of neutrophils plays a key role in reperfusion injury. However, the mechanism of the P-selectin induction is not known. Here we show that infarct size after ischemia/reperfusion was significantly smaller in mice lacking guanylyl cyclase-A (GC-A), a natriuretic peptide receptor. The decrease was accompanied by decreases in neutrophil infiltration in coronary endothelial P-selectin expression. Pretreatment with HS-142-1, a GC-A antagonist, also decreased infarct size and P-selectin induction in wild-type mice. In cultured endothelial cells, activation of GC-A augmented H2O2-induced P-selectin expression. Furthermore, ischemia/reperfusion-induced activation of NF-kappaB, a transcription factor that is known to promote P-selectin expression, is suppressed in GC-A-deficient mice. These results suggest that inhibition of GC-A alleviates ischemia/reperfusion injury through suppression of NF-kappaB-mediated P-selectin induction. This novel, GC-A-mediated mechanism of ischemia/reperfusion injury may provide the basis for applying GC-A blockade in the clinical treatment of reperfusion injury.

The neuron-restrictive silencer element-neuron-restrictive silencer factor system regulates basal and endothelin 1-inducible atrial natriuretic peptide gene expression in ventricular myocytes.

Induction of the atrial natriuretic peptide (ANP) gene is a common feature of ventricular hypertrophy. A number of cis-acting enhancer elements for several transcriptional activators have been shown to play central roles in the regulation of ANP gene expression, but much less is known about contributions made by transcriptional repressors. The neuron-restrictive silencer element (NRSE), also known as repressor element 1, mediates repression of neuronal gene expression in nonneuronal cells. We found that NRSE, which is located in the 3' untranslated region of the ANP gene, mediated repression of ANP promoter activity in ventricular myocytes and was also involved in the endothelin 1-induced increase in ANP gene transcription. The repression was conferred by a repressor protein, neuron-restrictive silencer factor (NRSF). NRSF associated with the transcriptional corepressor mSin3 and formed a complex with histone deacetylase (HDAC) in ventricular myocytes. Trichostatin A (TSA), a specific HDAC inhibitor, relieved NRSE-mediated repression of ANP promoter activity, and chromatin immunoprecipitation assays revealed the involvement of histone deacetylation in NRSE-mediated repression of ANP gene expression. Furthermore, in myocytes infected with recombinant adenovirus expressing a dominant-negative form of NRSF, the basal level of endogenous ANP gene expression was increased and a TSA-induced increase in ANP gene expression was apparently attenuated, compared with those in myocytes infected with control adenovirus. Our findings show that an NRSE-NRSF system plays a key role in the regulation of ANP gene expression by HDAC in ventricular myocytes and provide a new insight into the role of the NRSE-NRSF system outside the nervous system.

Induction of JAB/SOCS-1/SSI-1 and CIS3/SOCS-3/SSI-3 is involved in gp130 resistance in cardiovascular system in rat treated with cardiotrophin-1 in vivo.

CIS (cytokine-inducible SH2 protein), SOCS (suppressor of cytokine signaling), or SSI (signal transducers and activators of transcription [STAT]-induced STAT inhibitor) proteins are a family of cytokine-inducible negative regulators of cytokine signaling via Janus kinase (JAK)-STAT pathways. Given the evidence that the JAK-STAT pathway plays a critical role in the cardiovascular system, the primary objective of this study was to assess the effects of the CIS family on JAK-STAT signaling in the cardiovascular system in rats treated with cardiotrophin-1 (CT-1), an interleukin-6 family of cytokines. Intravenous injection of 20 microgram/kg body weight of CT-1 induced a transient, marked increase in STAT3 activation in various tissues, including heart and lung, and subsequent upregulation of 2 members of the CIS family, JAK-binding protein (JAB)/SOCS-1/SSI-1 and CIS3/SOCS-3/SSI-3, in the same tissues. It was also observed that CIS3 was directly associated with JAK2 in vivo. Pretreatment with the same dose of CT-1 60 minutes before significantly attenuated the STAT3 activation induced by a second injection of CT-1. We previously reported that intravenous injection of CT-1 results in the nitric oxide (NO)-dependent hypotension accompanied by the induction of inducible NO synthase mRNA. In rats pretreated with CT-1, the induction of inducible NO synthase mRNA or hypotension by subsequent CT-1 injection was not observed. Forced expression of JAB or CIS3, but not other CISs, directly blocked CT-1-induced STAT3 activation in 293 cells. These results suggest that JAB and CIS3 serve as endogenous inhibitors of CT-1-mediated JAK-STAT signaling in the cardiovascular system in vivo.

Differences of gene expression in bovine alveolar macrophages infected with virulent and attenuated isogenic strains of Mycobacterium bovis.

Infection with Mycobacterium bovis is a significant human and animal health problem in many parts of the world. The first stage of pulmonary tuberculosis occurs after inhalation of the bacilli into an alveolus where they are ingested by resident macrophages. DNA microarray analysis was used to detect genes expressed in bovine lung alveolar macrophages infected with two isogenic strains of M. bovis, a virulent strain, ATCC35723 and an attenuated strain, WAg520 derived from ATCC35723. Chemokines, interleukin-8 and monocyte chemotactic protein 1, were more strongly expressed in ATCC35723-infected macrophages compared to WAg520-infected macrophages. Conversely, a group of genes, including fibrinogen-like protein 2 and legumain, were expressed at a higher level in macrophages infected with WAg520 compared to ATCC35723. Quantitative real-time PCR of a selected group of these differentially expressed genes confirmed enhanced levels of IL-8 mRNA in ATCC35723-infected macrophages compared to WAg520-infected macrophages. Microarray analysis of gene expression in macrophages infected with attenuated isogenic strains of M. bovis may identify key genes involved in early and protective immune responses to tuberculosis.