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Background Atypical sensory behavior disrupts behavioral adaptation in children with autism spectrum disorder (ASD); however, neural correlates of sensory dysfunction using magnetoencephalography (MEG) remain unclear. Method We used MEG to measure the cortical activation elicited by visual (uni)/audiovisual (multisensory) movies in 46 children (7–14 years) were included in final analysis: 13 boys with atypical audiovisual behavior in ASD (AAV+), 10 without this condition, and 23 age-matched typically developing boys. Results The AAV+ group demonstrated an increase in the cortical activation in the bilateral insula in response to unisensory movies and in the left occipital, right superior temporal sulcus (rSTS), and temporal regions to multisensory movies. These increased responses were correlated with severity of the sensory impairment. Increased theta-low gamma oscillations were observed in the rSTS in AAV+. Conclusion The findings suggest that AAV is attributed to atypical neural networks centered on the rSTS.

Charcot-Marie-Tooth disease type 4H (CMT4H) is an autosomal recessive inherited demyelinating neuropathy caused by an FYVE, RhoGEF, and a PH domain-containing protein 4 (FGD4) gene mutation. CMT4H is characterized by an early onset, slow progression, scoliosis, distal muscle atrophy, and foot deformities. We herein present sibling cases of CMT4H with a homozygous mutation in the FGD4 gene. Both patients exhibited cauda equina thickening on magnetic resonance imaging, which had not been reported among the previous CMT4H cases. This is the first report of CMT4H with a homozygous FGD4 c.1730G>A (p.Arg577Gln) mutation showing mild progression and cauda equina thickening.

Cereblon (CRBN) is a target for immunomodulatory drugs. This study investigated the prognostic value of the expression of CRBN‐pathway genes on the clinical relevance of lenalidomide (Len) treatment and evaluated the levels of CRBN‐binding proteins and mutations in these genes after Len treatment. Forty‐eight primary multiple myeloma cells were collected prior to treatment with Len and dexamethasone (Ld) and 25 paired samples were obtained post‐Ld therapy. These tumor cells were used to determine the expression and mutated forms of the CRBN‐pathway genes. Following normalization with CRBN levels, there was a significantly reduced IKZF1/CRBN ratio in samples that responded poorly to Ld therapy. Moreover, patients with low ratios of IKZF1/CRBN showed a significantly shorter progression‐free survival (PFS) and overall survival (OS) than those with higher ratios. However, patients with high ratios of KPNA2/CRBN showed a significantly shorter PFS and OS than patients with lower ratios. Of the 25 paired samples analyzed, most samples showed a reduction in the expression of CRBN and an increase in IKZF1 gene expression. No mutations were observed in CRBN, IKZF1, or CUL4A genes in the post‐Ld samples. In conclusion, a decreased expression of IKZF1 and increased expression of KPNA2 compared to that of CRBN mRNA predicts poor outcomes of Ld therapy., This study investigated the prognostic value of the expression of cereblon (CRBN)‐pathway genes on the clinical relevance of lenalidomide treatment and evaluated the levels of CRBN‐binding proteins, mutations in these genes, and the methylation status of the CRBN promoter sequence. In conclusion, a decreased expression of IKZF1 and increased expression of KPNA2 compared to that of CRBN mRNA predicts poor outcomes of lenalidomide and dexamethasone therapy.

Human mesenchymal stem cells can differentiate into various cell types and are useful for applications in regenerative medicine. Previous studies indicated that dental pulp exfoliated from deciduous teeth is a valuable alternative for dental tissue engineering because it contains stem cells with a relatively high proliferation rate. For clinical application, it is necessary to rapidly obtain a sufficient number of cells in vitro and maintain their undifferentiated state, however, the abundance of stem cells in the dental pulp tissue is limited. Non-thermal atmospheric pressure plasma (NTAPP) has been applied in regenerative medicine because it activates cell proliferation. Here, we examined the effects of NTAPP to activate the proliferation of human deciduous dental pulp fibroblast-like cells (hDDPFs) in vitro. Compared with untreated cells, NTAPP increased cell proliferation by 1.3-fold, significantly upregulated well-known pluripotent genes for stemness (e.g., Oct4, Sox2, and Nanog), and activated the expression of stem cell-specific surface markers (e.g., CD105). Overall, NTAPP activated the proliferation of various mesodermal-derived human adult stem cells while maintaining their pluripotency and stemness. In conclusion, NTAPP is a potential tool to expand the population of various adult stem cells in vitro for medical applications.

Chronic active Epstein-Barr virus infection (CAEBV) is a lymphoproliferative disorder characterized by the clonal proliferation of EBV-infected T or NK cells and is related to severe systemic inflammation. This study aims to investigate STAT3 to elucidate the mechanism underlying the CAEBV development. We determined that STAT3 was constitutively activated in EBV-positive T- or NK-cell lines. We also determined that STAT3 was activated in the peripheral blood mononuclear cells (PBMCs) containing EBV-infected clonally proliferating T or NK cells in six of seven patients with CAEBV. We conducted direct sequencing of the STAT3 Src homology 2 (SH2) domain, which has previously been reported to be mutated in T- or NK-cell neoplasms. No mutation was detected in the STAT3 SH2 domain in patients with CAEBV. Next, we investigated the effects of ruxolitinib, an inhibitor of both JAK1 and JAK2, which phosphorylates and activates STAT3. Ruxolitinib suppressed the phosphorylation of STAT3 in EBV-positive T- or NK-cell lines. Ruxolitinib also decreased the viable cell number of EBV-positive T- or NK-cell lines and PBMCs from patients with CAEBV. Furthermore, ruxolitinib suppressed the production of inflammatory cytokines in the cell lines and CAEBV patient-derived cells. In conclusion, constitutively activated STAT3, which promotes survival and cytokine production, could be a therapeutic target for CAEBV.

Proteasome inhibitors (PI), mainly targeting the β5 subunit of the 20S proteasome, are widely used in the treatment of multiple myeloma (MM). However, PI resistance remains an unresolved problem in the therapy of relapsed and refractory MM. To develop a new PI that targets other proteasome subunits, we examined the anti-MM activity of a novel syringolin analog, syringolog-1, which inhibits the activity of both the β5 and β2 subunits. Syringolog-1 exhibited marked cytotoxicity against various MM cell lines and anti-tumor activity towards bortezomib (Btz)-resistant MM cells through the dual inhibition of chymotrypsin-like (β5 subunit) and trypsin-like (β2 subunit) activities. MM cells, including Btz-resistant cells, showed elevated CHOP and NOXA expression after syringolog-1 treatment, indicating the induction of excessive endoplasmic reticulum stress during syringolog-1 treatment. Similar activities of syringolog-1 were also observed in freshly prepared MM cells derived from patients. To clarify the anti-tumor mechanism of dual inhibition of both the β5 and β2 subunits of the proteasome, PSMB5 and PSMB7 were co-inhibited in MM cells. This resulted in increased apoptosis of MM cells accompanied by accumulation of ubiquitinated proteins compared to inhibition of either PSMB7 or PSMB5 alone, indicating an enhanced effect by double inhibition of β2 and β5 activities. In conclusion, this syringolin analog, a dual inhibitor of proteasome β2 and β5 activities, exhibited potent anti-tumor effects on MM cells and may be useful for overcoming Btz-resistance in the treatment of MM.

We herein report the case of a 65-year-old woman diagnosed with myasthenia gravis (MG) after complaining of double vision. The patient had anti-low-density lipoprotein receptor-related protein 4 (LRP4) antibody in her serum, although antibodies against the acetylcholine receptor and muscle-specific tyrosine kinase were not detected. Chest computed tomography showed an anterior mediastinal tumor with a high uptake on fluorodeoxyglucose-positron emission tomography. Endoscopic thymectomy successfully ameliorated her ocular symptoms and showed the lesion to be thymoma. The present case revealed that anti-LRP4 antibody-associated MG can be associated with thymoma, which has been regarded as a rare complication of this disease thus far.

Monoclonal antibodies against surface antigens on MM cells, such as anti-SLAMF7 and anti-CD38 antibodies, represent an attractive therapeutic modality for the eradication of multiple myeloma (MM) cells. However, further exploration of target molecules is urgently needed for the development of more effective therapies. In the present study, we studied the expression of CD48 in a total of 74 primary MM samples derived from patients to evaluate SLAMF2 (CD48) as a candidate in mAb therapy for MM. Of 74 samples, 39 were subjected to SLAMF7 analysis. Most of the MM cells, defined as CD38 and CD138 double-positive cells, showed strong expression of CD48 or SLAMF7 independent of disease stage or treatment history. In these 39 samples, most MM cells showed expression of both SLAMF7 and CD48; however, several samples showed expression of either only CD48 or only SLAMF7, including seven cases that were only highly positive for SLAMF7, and five that were only highly positive for CD48. Our study demonstrates that the immune receptor CD48 is overexpressed on MM cells together with SLAMF7, and that CD48 may be considered as an alternative target for treatment of MM in cases showing weak expression of SLAMF7.

The compartmentalization of the cerebellum into modules is often used to discuss its function. What, exactly, can be considered a module, how do they operate, can they be subdivided and do they act individually or in concert are only some of the key questions discussed in this consensus paper. Experts studying cerebellar compartmentalization give their insights on the structure and function of cerebellar modules, with the aim of providing an up-to-date review of the extensive literature on this subject. Starting with an historical perspective indicating that the basis of the modular organization is formed by matching olivocorticonuclear connectivity, this is followed by consideration of anatomical and chemical modular boundaries, revealing a relation between anatomical, chemical, and physiological borders. In addition, the question is asked what the smallest operational unit of the cerebellum might be. Furthermore, it has become clear that chemical diversity of Purkinje cells also results in diversity of information processing between cerebellar modules. An additional important consideration is the relation between modular compartmentalization and the organization of the mossy fiber system, resulting in the concept of modular plasticity. Finally, examination of cerebellar output patterns suggesting cooperation between modules and recent work on modular aspects of emotional behavior are discussed. Despite the general consensus that the cerebellum has a modular organization, many questions remain. The authors hope that this joint review will inspire future cerebellar research so that we are better able to understand how this brain structure makes its vital contribution to behavior in its most general form.

Afuresertib (AFU), a novel inhibitor of the serine/threonine kinase AKT, has clinical efficacy as a monotherapy against hematological malignancies and is expected to be used in combination with standard therapies for multiple myeloma (MM). To develop a more effective and less toxic combination of immunomodulatory drugs (IMiDs) for therapy, the antitumor effect of sub-optimal doses of AFU, pomalidomide plus dexamethasone (PD), and the AFU-PD combination on MM cells were examined in the present study. Two MM cell lines, XG-7 and U266, with low sensitivity to both PD and AFU monotherapies, were subjected to these combinations and analyzed. Although the cell lines showed a slight reduction in viability with the sub-optimal doses of each monotherapy, the combination of the treatments resulted in a reduction in cell viability and the progression of apoptosis. Co-treatment with sub-optimal doses of PD and AFU enhanced caspase activation and highly suppressed the expression of IKZF1 and IKZF3. In addition, this combination promoted the dephosphorylation and stabilization of 4EBP1, an inhibitor of eIF4E activation, which led to the impairment of eIF4E-mediated translational activity. Furthermore, AFU showed a sufficient inhibitory effect on the phosphorylation of FOXO1, a tumor suppressor, in monotherapy or in combination with PD, which may be attributable to the activation of FOXO1, the subsequent inhibition of tumor growth, and the induction of cell death. In conclusion, the combination therapy with sub-optimal doses of PD and AFU exhibited potent antitumor activity in MM cells and may provide a novel strategy for the treatment of patients who experienced intolerable toxicity or insufficient response during IMiD therapy.

The cholinergic interneurons (CINs) of the striatum are crucial for normal motor and behavioral functions of the basal ganglia. Striatal CINs exhibit tonic firing punctuated by distinct pauses. Pauses occur in response to motivationally significant events, but their function is unknown. Here we investigated the effects of pauses in CIN firing on spiny projection neurons (SPNs) – the output neurons of the striatum – using in vivo whole cell and juxtacellular recordings in mice. We found that optogenetically-induced pauses in CIN firing inhibited subthreshold membrane potential activity and decreased firing of SPNs. During pauses, SPN membrane potential fluctuations became more hyperpolarized and UP state durations became shorter. In addition, short-term plasticity of corticostriatal inputs was decreased during pauses. Our results indicate that, in vivo, the net effect of the pause in CIN firing on SPNs activity is inhibition and provide a novel mechanism for cholinergic control of striatal output., eLife digest Nerve cells or neurons communicate with one another using electrical impulses and chemical messengers called neurotransmitters. Additional molecules known as neuromodulators regulate the communication process. In contrast to neurotransmitters, neuromodulators do not send messages directly from one neuron to the next. Instead they change the way that neurons respond to neurotransmitters. For example, the neuromodulator acetylcholine is most abundant in a region called the striatum. Located deep within the brain, the striatum contributes to learning and memory, motivation, and movement. Studies in rodents show that neurons within the striatum called cholinergic interneurons are almost continuously active. Each time these cells fire, they release acetylcholine. But whenever an animal experiences something unusual or important, the interneurons temporarily stop firing. Zucca et al. wanted to know whether these pauses in firing also act as a signal within the striatum. To find out, Zucca et al. inserted a light-sensitive ion channel into cholinergic interneurons in the mouse striatum. Activating the ion channels with a laser beam stopped the interneurons from firing. Zucca et al. showed that these pauses in firing reduced the activity of another group of neurons, the spiny projection neurons. These are the major output neurons of the striatum. They send messages from the striatum to other parts of the brain. The results thus suggest that cholinergic interneurons signal notable events by temporarily blocking output from the striatum. Understanding how cholinergic interneurons work will help reveal how the striatum drives behavior. It may also lead to treatments for diseases caused by cholinergic system dysfunction. Many patients with Parkinson’s disease or schizophrenia take medicines to block the effects of acetylcholine. Understanding how acetylcholine affects the striatum may help clarify how these treatments work.

The ability to change strategies in different contexts is a form of behavioral flexibility that is crucial for adaptive behavior. The striatum has been shown to contribute to certain forms of behavioral flexibility such as reversal learning. Here we report on the contribution of striatal cholinergic interneurons—a key element in the striatal neuronal circuit—to strategy set-shifting in which an attentional shift from one stimulus dimension to another is required. We made lesions of rat cholinergic interneurons in dorsomedial or ventral striatum using a specific immunotoxin and investigated the effects on set-shifting paradigms and on reversal learning. In shifting to a set that required attention to a previously irrelevant cue, lesions of dorsomedial striatum significantly increased the number of perseverative errors. In this condition, the number of never-reinforced errors was significantly decreased in both types of lesions. When shifting to a set that required attention to a novel cue, rats with ventral striatum lesions made more perseverative errors. Neither lesion impaired learning of the initial response strategy nor a subsequent switch to a new strategy when response choice was indicated by a previously relevant cue. Reversal learning was not affected. These results suggest that in set-shifting the striatal cholinergic interneurons play a fundamental role, which is dissociable between dorsomedial and ventral striatum depending on behavioral context. We propose a common mechanism in which cholinergic interneurons inhibit neurons representing the old strategy and enhance plasticity underlying exploration of a new rule.

The importance of the cerebellum in control of locomotion is demonstrated by the ataxic gait of cerebellar patients. The intermediate cerebellum contains somatotopical representations for forelimbs and hindlimbs in both anterior and posterior lobes. However, it is not known whether these separate regions have discrete roles in control of limb movements during locomotion. Here we compared the effect of muscimol-induced inactivation of the anterior or posterior intermediate cerebellum on limb movements in walking rats. Inactivation of the anterior intermediate cerebellum had clear effects on limb movements during overground locomotion, resulting in excessive toe elevation and hyperflexion of joints in the swing phase. Inactivation of the posterior region resulted in similar but less pronounced deficits. Postural defects were not present in either group of rats. These findings suggest that the intermediate cerebellum of the anterior lobe has a greater influence on the ability to control limb movements during overground locomotion than the posterior lobe.

In the original version of this paper, the Title should have been written with “A Consensus paper” to read “Cerebellar Modules and Their Role as Operational Cerebellar Processing Units: A Consensus paper”.

Cortico-basal ganglia-thalamocortical loops are largely conceived as parallel circuits that process limbic, associative, and sensorimotor information separately. Whether and how these functionally distinct loops interact remains unclear. Combining genetic and viral approaches, we systemically mapped the limbic and motor cortico-basal ganglia-thalamocortical loops in rodents. Despite largely closed loops within each functional domain, we discovered a unidirectional influence of the limbic over the motor loop via ventral striatum-substantia nigra (SNr)-motor thalamus circuitry. Slice electrophysiology verifies that the projection from ventral striatum functionally inhibits nigro-thalamic SNr neurons. In vivo optogenetic stimulation of ventral or dorsolateral striatum to SNr pathway modulates activity in medial prefrontal cortex (mPFC) and motor cortex (M1), respectively. However, whereas the dorsolateral striatum-SNr pathway exerts little impact on mPFC, activation of the ventral striatum-SNr pathway effectively alters M1 activity. These results demonstrate an open cortico-basal ganglia loop whereby limbic information could modulate motor output through ventral striatum control of M1.

Behavioral flexibility is crucial for survival in changing environments. Broadly defined, behavioral flexibility requires a shift of behavioral strategy based on a change in governing rules. We describe a strategy set-shifting task that requires an attentional shift from one stimulus dimension to another. The paradigm is often used for testing cognitive flexibility in primates. However, the rodent version has not been as extensively developed. We have recently extended an established set-shifting task in the rat1 by requiring attention to different stimuli according to context. All the experimental conditions required animals to choose either a left or right lever. Initially, all animals had to choose on the basis of the location of the lever. Subsequently, a change in the rule occurred, which required a shift in set from location-based rule to a rule in which the correct lever was indicated by a light cue. We compared performance on three different versions of the task, in which the light stimulus was either novel, previously relevant, or previously irrelevant. We found that specific neurochemical lesions selectively impaired the ability to make particular types of set shift as measured by the performance on the different versions of the task.

Distinct reflected waves (S × S) are observed in the northern Kinki district, southwestern Japan. We conducted a high-resolution reflection analysis by using data from 128 seismic stations with an average spacing of about 5 km. We used a stacking method to obtain three-dimensional distributions of relative reflection strengths of S waves and found a thin planar zone of high reflection strengths at depths of 25-30 km, which we call a S wave reflector. We also found that the zone of high reflection strengths is dipping to the north and that low-frequency earthquakes (LFEs) occurred near the edge of the zone at depths around the Moho discontinuity. It is inferred from these results that fluid is concentrated in this zone of high reflection strengths. It is likely that the zone of high reflection strengths is a path of fluid upwelling from the mantle, together with the hypocentral region of LFEs, that is located near the lower edge of the zone. The northern Kinki district is thought to be part of the Niigata-Kobe Tectonic Zone (NKTZ) high strain rates region. The high reflection strengths zone may be associated with high strain rates in the NKTZ.

Acetylcholine is one of the major neurotransmitters in the brain. The highest density of cholinergic markers is found in the striatum, a basal ganglia region that has been associated with behavioral flexibility. In our recent study, we showed a causal role of the cholinergic interneurons of the striatum in set-shifting in the rat. The set-shifting task required an attentional shift from one stimulus dimension to another, in order to respond appropriately after a change of governing rules. In the experiment the cholinergic interneurons were ablated by a specific immunotoxin injected into either the dorsomedial or ventral striatum, and the effects of the lesions on set-shift performance were measured. Neither lesion had an effect on initial discrimination in which rats had to learn a strategy based on lever location. However, when rats encountered a rule change after the set-shift, lesioned animals were more likely to persist in using an old strategy, and less likely to explore new strategies. Dorsomedial cholinergic ablation impaired a shift of set that required attention to the previously irrelevant stimulus. On the other hand, ventral cholinergic lesions had an effect on shifting a strategy when a novel stimulus was introduced as a new important cue. These observations suggested a specific role of striatal acetylcholine in set-shifting: suppression of a previously correct but now invalid strategy and exploration for a new rule. Both dorsomedial and ventral striatal cholinergic systems appear to play this role, but in different contexts.

Walking smoothly and safely often involves stepping over an obstacle. The purpose of this study was to examine forelimb movements and toe trajectories in stepping over an obstacle during overground locomotion in rats. We performed a kinematic analysis of forelimb movements and measured electromyographic (EMG) activities in the biceps and triceps brachii of the forelimbs. We found that mean toe height just above the obstacle was lower in the leading forelimb than in the trailing forelimb. The toe positions of the leading forelimb at maximal elevation over the obstacle (peak toe position) were closer to the upper edge of the obstacle than those of the trailing forelimb. The linear distance between peak toe position and the upper edge of the obstacle was significantly less in the leading forelimb compared to the trailing forelimb. The peak toe position of the leading forelimb spatially corresponds to the transition point from flexion to extension of the elbow joint. This transition appeared to be controlled mainly by an offset of EMG activity of the elbow flexor, the biceps brachii muscle. In contrast, the trailing forelimb appeared to be controlled by the shoulder and wrist joints. These results suggest that the toe trajectory of the leading forelimb is more accurately regulated than that of the trailing forelimb. In addition, the activities of the elbow flexor may in part contribute to the toe trajectory of the leading forelimb.

In 75% (v/v) DMSO/H2O solvent mixture, salt effects on the solvolysis reaction rates of haloalkanes and related compounds (RX) have been examined. In spite of the decreased water activity in the so...

Stepping over obstacles to avoid tripping is an essential component in safe and smooth locomotion. Obstacle avoidance during locomotion is completed in several steps during the approach phase toward the obstacle and stepping over the obstacle. The purpose of this study was to investigate gait modification during the approach phase when stepping over obstacles of different heights in rats. In all four limbs, the toe height when the toe was just above the obstacle increased depending on the obstacle height, leaving a safe margin. However, the horizontal distance between toe and obstacle just prior to stepping over was not influenced by obstacle height. In the fore- and hindlimbs that served as trailing limbs, it was found that the stride length and its related swing phase duration in the final step were significantly shorter than those in both the penultimate step and overground locomotion. These results suggest that adjustment of trailing limb in the final step during the approach phase is important in preparation for the stepping movement over an obstacle.

One of the main hallmarks of Alzheimer's disease (AD) is senile plaques composed of amyloid β (Aβ). We developed a new edible vaccine: rice expressing GFP-Aβ42. In a previous report, we described the production of anti-Aβ antibodies in B6 mice fed Aβ rice mixed with cholera toxin B subunit (CTB). In this report, we investigated whether Aβ rice had therapeutic effects in the Tg2576 AD model mice. The anti-Aβ antibody titer was increased and levels of intracerebral Aβ (soluble and insoluble) and serum Aβ decreased. Because the value of IgG1/IgG2a in the Aβ feeding group was >1, immunization via Aβ rice may induce a non-inflammatory Th2 reaction. We also found that the Aβ vaccine improved memory, as assessed in a Y-maze test. The number of arm entries in the Y-maze test was lower in the Aβ feeding group than in the control group. These results suggest that the new edible vaccine Aβ rice may have therapeutic effects in AD.

In order to investigate the effect of sintering temperatures and applied pressures on hardness and magnetic properties of the aluminum-based composite bulk materials possessing magnetic properties, composite powders were consolidated into the bulk materials at different sintering temperatures and applied pressures by spark plasma sintering (SPS). Solid-state reaction, hardness and magnetic properties of the composite bulk materials were characterised by X-ray diffraction, Vickers hardness and vibrating sample magnetometer, respectively. Change in constituent phases of the composite bulk materials fabricated at different sintering temperatures and applied pressures were observed. In addition, change in the amount of the intermetallic compounds of the composite bulk materials fabricated at different applied pressures was observed. The Vickers hardness of the composite bulk materials fabricated at 88 MPa was higher than that at 49 MPa due to the large amount of the Al13Fe4 and higher relative density. The magnetization of the composite bulk materials fabricated at 723 K and 773 K was corresponded to the amount of ZnO. In addition, the magnetization of the composite bulk materials fabricated at 823 K was dramatically decreased due to the formation of Al13Fe4. Effect of sintering temperatures and applied pressures on hardness and magnetic properties of the composite bulk materials was identified due to the change in the amount of the intermetallic compounds and relative density.

In order to fabricate Mg-based composite powders with high hardness and hard magnetic properties, pure magnesium and barium ferrite powders were mechanically alloyed (MAed) using a vibrational ball mill.Change in Vickers micro-hardness of the pure magnesium powders as a function of the mechanical milling (MM) times obeyed the crystallite size. Change in Vickers micro-hardness of the composite powders as a function of the amount of barium ferrite obeyed the rule of mixture when the MA time was 120 and 240 min.. On the other hands, change in Vickers micro-hardness of the composite powders as a function of the amount of barium ferrite wasn't obeyed the rule of mixture when the MA time was 20 and 60 min.. Magnetization of the composite powders obeyed the amount of the barium ferrite powder, whereas coercive force of the MAed powders decreased due to the refinement of the barium ferrite powder.Mg-based composite powders with high hardness and hard magnetic properties were successfully produced by mechanical alloying.

In order to possess magnetic properties in the Mg-based composite materials, pure magnesium and Ni–Cu–Zn ferrite (FR) powders were mechanically alloyed (MAed) using a vibrational ball mill, and the produced composite powders were consolidated into the bulk materials by spark plasma sintering (SPS) . Solid-state reaction, hardness, microstructure and magnetic properties of the bulk materials were characterised by X-ray diffraction, Vickers hardness, optical microscopy and vibrating sample magnetometer, respectively. Solid-state reactions between Mg and FR in the bulk materials occurred to form α-Fe and MgO at a sintering temperature of 673 K. In contrast, the formation of Fe3C occurred at 773 K and 873 K. The Vickers hardness of the bulk materials fabricated from MAed 8 h powder at 773 K showed the highest value of 198 HV. This is due to an increase of composite phases formed the intermetallic compounds, such as MgO, α-Fe and Fe3C as increasing MA time. The magnetic property (magnetization) of the bulk materials fabricated at 673 K exhibited the highest value of 1.0×10−5 Wbm/kg due to the formation of α-Fe. The magnetic property (magnetization) of the bulk materials decreased due to the formation of Fe3C as increasing sintering temperature. Ferromagnetism of the Mg-based composite materials was enhanced by the formation of the α-Fe and Fe3C.

In order to fabricate Mg-based composite powders possessing magnetic properties, pure magnesium and Ni–Cu–Zn ferrite powders were mechanically alloyed (MAed) using a vibrational ball mill. Change in Vickers microhardness of the pure magnesium powders as a function of the mechanical milling (MM) times obeyed the Hall–Petch relation. Change in Vickers microhardness of the composite powders as a function of the amount of Ni–Cu–Zn ferrite obeyed the rule of mixture when the MA time was 2 h. On the other hands, a slope of Vickers microhardness of the composite powders as a function of the amount of Ni–Cu–Zn ferrite was higher than that of a theoretical value calculated from the rule of mixture when the MA time was 4 h and 8 h. Magnetization of the composite powders obeyed the amount of the Ni–Cu–Zn ferrite powder, whereas no systematic change for coercive force was observed. Mg-based composite powders exhibiting magnetic properties were successfully produced by mechanical alloying.

In order to fabricate the Al-based composite materials possessing magnetic properties, air-atomized pure aluminium powder together with Ni-Cu-Zn Ferrite (FR) powder was mechanically alloyed (MAed) using a vibrational ball mill, and the MAed composite powders were consolidated into bulk materials by spark plasma sintering (SPS). Changes in constituent phases, particle size, hardness and soft magnetic properties of both the MAed powders and SPS materials were examined by X-ray diffraction (XRD), scanning electron microscopy (SEM), hardness measurements and vibrating sample magnetometry (VSM), respectively.No solid-state reactions could be detected by XRD in the MAed powders. The Vickers microhardness of the MAed powders increased by increase in MA time. The saturation magnetic flux density for the MAed powders were found to depend only upon the amount of the FR powder present. Ni-Cu-Zn Ferrite was decomposed to form ZnO when the MAed powder was sintered at 673 K and 773 K by SPS, whereas Al13Fe4 and Al4C3 were detected when the MAed powder was sintered at 873 K. The highest saturation magnetic flux density was obtained when the MAed powder were consolidated at 773 K.

Air-atomized pure aluminum powder together with Fe2ZnNiCuO6 (FR) powder was mechanically alloyed (MAed) using a vibrational ball mill, and the MAed composite powders were consolidated into bulk materials by spark plasma sintering (SPS) in order to fabricate the Al-based composite materials having magnetic properties. Changes in hardness, constituent phases and soft magnetic properties of both the MAed powders and SPS materials were examined by microhardness measurements, X-ray diffraction (XRD) and vibrating sample magnetometry (VSM), respectively. The Vickers microhardness of the MAed powders increased by both increase in MA time and the amount of FR powder addition. No solid-state reactions could be detected in the MAed powders. The saturation magnetic flux density for the MAed powders were found to depend only on the amount of the FR powder present. The coercive force was suppressed by MA processing for FR powder with the present of aluminum. FR was decomposed to ZnO when the MAed powder was SPSed at 673 K and 773 K, whereas Al13Fe4, α-Al2O3 and Al4C3 were detected when the MAed powder was SPSed at temperatures above 873 K. Therefore, magnetic properties with the SPS material fabricated at 773 K was shown. In fabricating aluminum based composite materials having magnetic properties, the best SPS condition was showed at 773 K.

The mammalian constitutive androstane receptor (CAR) is a transcription factor that participates in controlling the expression of xenobiotic metabolizing and transporting genes in response to xenobiotics in an organ-specific manner. In addition to the wild-type CAR (CAR WT) mRNA, mRNAs for five splice variants (SVs) could be detected in the liver of 7-week-old male Wistar rats by RT-PCR using primer pairs covering a full-length mRNA derived from 9 exons; insertion of 18 bp at the 5'-end of intron 8 with or without deletion of 3 bp from the 5'-end of exon 7 (CAR SV1 or SV2), deletion of 4 bp from the 5'-end of exon 8 (CAR SV3), insertion of 195 bp intron 7 (CAR SV4), and insertion of 91 bp intron 6 (CAR SV5). In contrast, only CAR SV5 was detected in lung. Due to the introduction of novel stop codons, all the SVs were considered to code for premature proteins. The liver homogenate gave two protein bands in the vicinity of 37 kDa on Western blotting. They were attributable to CAR WT and SV-complex, respectively, based on their putative molecular weights in descending order. Upon cotransfection with the reporter plasmid, only the cells transfected with the CAR SV4-expression plasmid showed enhanced luciferase activity similar to the WT-transfected cells, for which the further splicing of the remaining intron 7 seemed to be responsible. The transactivation-defective SVs downregulated CAR WT-induced luciferase activity to some extent in the cotransfection experiments.

The mammalian constitutively active receptor (CAR) is a ligand-activated transcription factor that participates in controlling the expression of cytochrome P450 2B (CYP2B) genes in response to xenobiotics in an organ-specific manner. In the presence of phenobarbital (PB) or PB-type agents, hepatic CYP2B forms are highly inducible. In contrast, PB-dependent increases in the expression of CYP2B activities are rarely observed in the lung. Mature CAR mRNA could be detected in the liver of 7-week-old Wistar rats by RT-PCR, while lung CAR mRNA had a 91 bp extra nucleotide sequence inserted in a coding region of hepatic CAR mRNA. By comparing the full- length sequence of hepatic CAR mRNA, including 5′- and 3′-untranslated region (3′-UTR), with the genomic sequence completed in the present study, the genomic structure was clarified to consist of 9 exons and 8 introns, in which the coding region expanded from exon 2 in close to its 5′-end to the first one-third of exon 9 after 159 bp of 5′-UTR in the most frequently obtained cDNA clones. In pulmonary CAR mRNA, intron 6 was not spliced out, implying that the lack of CAR in the lung might in part result from the incomplete splicing of precursor mRNA during its maturation.