Voltage-Controlled Magnon Transistor via Tuning Interfacial Exchange Coupling.

Magnon transistors that can effectively regulate magnon transport by an electric field are desired for magnonics, which aims to provide a Joule-heating free alternative to the conventional electronics owing to the electric neutrality of magnons (the key carriers of spin-angular momenta in the magnonics). However, also due to their electric neutrality, magnons have no access to directly interact with an electric field and it is thus difficult to manipulate magnon transport by voltages straightforwardly. Here, we demonstrated a gate voltage (V_{g}) applied on a nonmagnetic metal and magnetic insulator (MI) interface that bent the energy band of the MI and then modulated the probability for conduction electrons in the nonmagnetic metal to tunnel into the MI, which can consequently enhance or weaken the spin-magnon conversion efficiency at the interface. A voltage-controlled magnon transistor based on the magnon-mediated electric current drag (MECD) effect in a Pt-Y_{3}Fe_{5}O_{12}-Pt sandwich was then experimentally realized with V_{g} modulating the magnitude of the MECD signal. The obtained efficiency (the change ratio between the MECD voltage at ±V_{g}) reached 10%/(MV/cm) at 300 K. This prototype of magnon transistor offers an effective scheme to control magnon transport by a gate voltage.

Depth-Resolved Magnetization Dynamics Revealed by X-Ray Reflectometry Ferromagnetic Resonance.

Magnetic multilayers offer diverse opportunities for the development of ultrafast functional devices through advanced interface and layer engineering. Nevertheless, a method for determining their dynamic properties as a function of depth throughout such stacks has remained elusive. By probing the ferromagnetic resonance modes with element-selective soft x-ray resonant reflectivity, we gain access to the magnetization dynamics as a function of depth. Most notably, using reflectometry ferromagnetic resonance, we find a phase lag between the coupled ferromagnetic layers in [CoFeB/MgO/Ta]_{4} multilayers that is invisible to other techniques. The use of reflectometry ferromagnetic resonance enables the time-resolved and depth-resolved probing of the complex magnetization dynamics of a wide range of functional magnetic heterostructures with absorption edges in the soft x-ray wavelength regime.

Magnon Valve Effect between Two Magnetic Insulators.

The key physics of the spin valve involves spin-polarized conduction electrons propagating between two magnetic layers such that the device conductance is controlled by the relative magnetization orientation of two magnetic layers. Here, we report the effect of a magnon valve which is made of two ferromagnetic insulators (YIG) separated by a nonmagnetic spacer layer (Au). When a thermal gradient is applied perpendicular to the layers, the inverse spin Hall voltage output detected by a Pt bar placed on top of the magnon valve depends on the relative orientation of the magnetization of two YIG layers, indicating the magnon current induced by the spin Seebeck effect at one layer affects the magnon current in the other layer separated by Au. We interpret the magnon valve effect by the angular momentum conversion and propagation between magnons in two YIG layers and conduction electrons in the Au layer. The temperature dependence of the magnon valve ratio shows approximately a power law, supporting the above magnon-electron spin conversion mechanism. This work opens a new class of valve structures beyond the conventional spin valves.

HLA-B*13:01 and the dapsone hypersensitivity syndrome.

BACKGROUND: Dapsone is used in the treatment of infections and inflammatory diseases. The dapsone hypersensitivity syndrome, which is associated with a reported mortality of 9.9%, develops in about 0.5 to 3.6% of persons treated with the drug. Currently, no tests are available to predict the risk of the dapsone hypersensitivity syndrome. METHODS: We performed a genomewide association study involving 872 participants who had received dapsone as part of multidrug therapy for leprosy (39 participants with the dapsone hypersensitivity syndrome and 833 controls), using log-additive tests of single-nucleotide polymorphisms (SNPs) and imputed HLA molecules. For a replication analysis, we genotyped 24 SNPs in an additional 31 participants with the dapsone hypersensitivity syndrome and 1089 controls and performed next-generation sequencing for HLA-B and HLA-C typing at four-digit resolution in an independent series of 37 participants with the dapsone hypersensitivity syndrome and 201 controls. RESULTS: Genomewide association analysis showed that SNP rs2844573, located between the HLA-B and MICA loci, was significantly associated with the dapsone hypersensitivity syndrome among patients with leprosy (odds ratio, 6.18; P=3.84×10(-13)). HLA-B*13:01 was confirmed to be a risk factor for the dapsone hypersensitivity syndrome (odds ratio, 20.53; P=6.84×10(-25)). The presence of HLA-B*13:01 had a sensitivity of 85.5% and a specificity of 85.7% as a predictor of the dapsone hypersensitivity syndrome, and its absence was associated with a reduction in risk by a factor of 7 (from 1.4% to 0.2%). HLA-B*13:01 is present in about 2 to 20% of Chinese persons, 1.5% of Japanese persons, 1 to 12% of Indians, and 2 to 4% of Southeast Asians but is largely absent in Europeans and Africans. CONCLUSIONS: HLA-B*13:01 was associated with the development of the dapsone hypersensitivity syndrome among patients with leprosy. (Funded by the National Natural Science Foundation of China and others.).

Molecular characterization of carbapenemase genes in Acinetobacter baumannii in China.

Acinetobacter baumannii is an aerobic non-motile Gram-negative coccobacillus, and it is one of the most important nosocomial pathogens worldwide. The aim of this study was to determine the molecular epidemiology of the outbreak strains. Between March 2011 and March 2014, a total of 205 strains of A. baumannii were isolated from patients at the Nanyang City Center Hospital. The blaOXA-23, blaOXA-24, blaOXA-51, and blaOXA-58 genes were amplified by multiplex polymerase chain reaction. We found that 68 (33.17%) strains were positive for the blaOXA-23 gene, and 88.24% of these 68 showed resistance to carbapenems, while 11.76% were sensitive to carbapenems. The blaOXA-51 gene was found in 132 (64.39%) strains, and 17.42% of these were resistant to carbapenems while 82.58% were sensitive to carbapenems. Moreover, 5 (2.44%) strains were positive for blaOXA-58, of which 80% were resistant to carbapenems and 20% were sensitive to carbapenems. We found that A. baumannii showed 100% drug resistance to ampicillin, cefotetan, cefazolin, and cefoperazone. Our findings suggest that the blaOXA-23 and blaOXA-51 genes are most frequently identified in A. baumannii, while blaOXA-23 is the most important gene for resistance to carbapenems.

Single nucleotide polymorphisms in NOS2A and NOS3 genes are not associated with treatment response of non-small cell lung cancer patients following the definitive radiochemotherapy.

Nitric oxide (NO), is endogenously synthesized from L-arginine by nitric oxide synthase (NOS), exhibits a dual role in sensitivity to radiotherapy and chemotherapy of cancer cells. The aim of this study was to evaluate the influence of polymorphisms in NOS genes on treatment response of non-small-cell lung cancer (NSCLC) patients after radiochemotherapy. A cohort of 198 NSCLC patients treated with radiochemotherapy between 2009 and 2011 were included in this study. Genotyping analyses of 35 SNPs ( NOS2A, 21 and NOS3, 14) in each sample were conducted by using the Sequenom MassArray system. Unconditional logistic regression was performed to assess the association between treatment response and each genotype while adjusting or not for other covariates. Of 198 patients, 87 (43.9%) had objective responses, and 111(56.1%) did not respond. We observed no significant associations between treatment response and each genotype. While adjusting for other covariates, the associations were also not significant. Our results suggest that genetic variations within the NOS2A and NOS3 genes may not influence the treatment response in NSCLC patients with radiochemotherapy. Future studies in this problem are required to confirm our findings.

TGF-beta1 promotes microglial amyloid-beta clearance and reduces plaque burden in transgenic mice.

Abnormal accumulation of the amyloid-beta peptide (Abeta) in the brain appears crucial to pathogenesis in all forms of Alzheimer disease (AD), but the underlying mechanisms in the sporadic forms of AD remain unknown. Transforming growth factor beta1 (TGF-beta1), a key regulator of the brain's responses to injury and inflammation, has been implicated in Abeta deposition in vivo. Here we demonstrate that a modest increase in astroglial TGF-beta1 production in aged transgenic mice expressing the human beta-amyloid precursor protein (hAPP) results in a three-fold reduction in the number of parenchymal amyloid plaques, a 50% reduction in the overall Abeta load in the hippocampus and neocortex, and a decrease in the number of dystrophic neurites. In mice expressing hAPP and TGF-beta1, Abeta accumulated substantially in cerebral blood vessels, but not in parenchymal plaques. In human cases of AD, Abeta immunoreactivity associated with parenchymal plaques was inversely correlated with Abeta in blood vessels and cortical TGF-beta1 mRNA levels. The reduction of parenchymal plaques in hAPP/TGF-beta1 mice was associated with a strong activation of microglia and an increase in inflammatory mediators. Recombinant TGF-beta1 stimulated Abeta clearance in microglial cell cultures. These results demonstrate that TGF-beta1 is an important modifier of amyloid deposition in vivo and indicate that TGF-beta1 might promote microglial processes that inhibit the accumulation of Abeta in the brain parenchyma.

Identification of two novel splice mutations of the ADAR1 gene in two Chinese families with dyschromatosis symmetrica hereditaria.

Dyschromatosis symmetrica hereditaria (DSH) is a rare, autosomal dominant dermatosis, characterized by a mixture of hyperpigmented and hypopigmented macules on the dorsa of the hands and feet. The DSH locus has been mapped to chromosome 1q21, and in 2003, pathogenic mutations were identified in the ADAR1 (adenosine deaminase acting on RNA1) gene. In this study, we performed mutation detection of the ADAR1 gene in two Chinese families with DSH. PCR and direct sequencing of the ADAR1 gene were used to identify and confirm the mutations in the two families. Furthermore, we analysed the RNA transcripts by reverse transcriptase (RT)-PCR. Two aberrant splice products were confirmed with RT-PCR and DNA direct sequence analysis. These novel findings further extend our understanding of the role of ADAR1 in DSH.

Impact of serum FGF23 levels on blood pressure of patients with chronic kidney disease.

OBJECTIVE: To investigate the impact of serum FGF23 levels on blood pressure of patients with chronic kidney disease (CKD). PATIENTS AND METHODS: 128 patients with chronic kidney disease were selected from February 2013 to January 2016. Using CKD staging method, all the patients were divided into 1 to 5 stages according to the glomerular filtration rate. Enzyme-Linked ImmunoSorbent Assay (ELISA) was used to detect serum FGF23 levels of CKD patients and healthy control subjects. 24 h blood pressure monitoring method was used to monitor the mean arterial pressure of patients. Spearman-related analysis method was used to statistically analyze serum FGF23 level, mean arterial pressure and glomerular filtration rate. RESULTS: The serum FGF23 levels of CKD patients were significantly higher than those of the healthy control subjects (p<0.05). Also, FGF23 expression levels in serum were positively correlated with mean arterial pressure based on the results of the Spearman-related analysis. On the other hand, FGF23 expression levels in serum were negatively correlated with glomerular filtration rate. The FGF23 expression levels in serum of the patients were significantly decreased along with the decrease of mean arterial pressure. CONCLUSIONS: Serum FGF23 level is positively correlated with mean arterial pressure and negatively correlated with glomerular filtration rate. So, FGF23 has an important clinical significance that can reflect blood pressure and treatment effect of dialysis of CKD patients.

[Surveillance on drinking-water-born endemic fluorosis in China, 2013].

OBJECTIVE: To investigate the prevalence of fluorosis and related control measures on drinking water type of endemic fluorosis in China. METHODS: According to the national program- "Surveillance Scheme of Drinking-Water-Borne Endemic Fluorosis" , 136 counties were selected in 29 provinces, autonomous regions and municipalities. Three epidemic villages were randomly selected as fixed monitoring sites in each county. Dental fluorosis of all the children aged 8-12 living in the villages under the monitoring program, was identified under the ariteria from "Diagnosis of dental fluorosis" (WS/T 208-2011). Operating conditions and contents of fluoride in all the'water-improved projects' were investigated. Contents of fluoride in drinking water were tested in villages without the 'water-improved projects'. "Standard Test Method for Drinking Water" (GB/T 5750.5-2006) was used to detect the water fluoride. RESULTS: The overall prevalence of dental fluorosis among children aged 8-12 in all the villages under monitor program, was 28.58% (7 950/27 817), with the dental fluorosis index (DFI) as 0.58. Among them, the prevalence was 22.28% (3 917/17 583) and DFI was 0.44 in the'water-improved projects' villages that under normal operation and with qualified fluoride contents. The prevalence appeared as 38.74% (1 926/4 971) with DFI as 0.84 in those villages with 'water-improved projects' but mal-operated or with excessive fluoride. The prevalence was 40.03% (2 107/5 263), and DFI was 0.81 in those villages without 'water-improved projects'. The prevalence rates of dental fluorosis in children from the three types of endemic areas were significantly different. For 'water-improved projects', the normal opration rate was 93.77% (286/305) and the qualification rate of fluoride content was 76.77% (228/297). CONCLUSIONS: Dental fluorosis in children living in the drinking-water-born endemic fluorosis areas was on the edge of epidemics in China. Effective improvement on the quality of drinking water can significantly reduce the severity of dental fluorosis in children. The rate of proper operation on 'water-improved projects' was near to 95% in the endemic area. However, rate that met the criteria on qualified fluoride contents of these projects was still below 80%.

High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation.

Amyloid plaques are a neuropathological hallmark of Alzheimer's disease (AD), but their relationship to neurodegeneration and dementia remains controversial. In contrast, there is a good correlation in AD between cognitive decline and loss of synaptophysin-immunoreactive (SYN-IR) presynaptic terminals in specific brain regions. We used expression-matched transgenic mouse lines to compare the effects of different human amyloid protein precursors (hAPP) and their products on plaque formation and SYN-IR presynaptic terminals. Four distinct minigenes were generated encoding wild-type hAPP or hAPP carrying mutations that alter the production of amyloidogenic Abeta peptides. The platelet-derived growth factor beta chain promoter was used to express these constructs in neurons. hAPP mutations associated with familial AD (FAD) increased cerebral Abeta(1-42) levels, whereas an experimental mutation of the beta-secretase cleavage site (671(M-->I)) eliminated production of human Abeta. High levels of Abeta(1-42) resulted in age-dependent formation of amyloid plaques in FAD-mutant hAPP mice but not in expression-matched wild-type hAPP mice. Yet, significant decreases in the density of SYN-IR presynaptic terminals were found in both groups of mice. Across mice from different transgenic lines, the density of SYN-IR presynaptic terminals correlated inversely with Abeta levels but not with hAPP levels or plaque load. We conclude that Abeta is synaptotoxic even in the absence of plaques and that high levels of Abeta(1-42) are insufficient to induce plaque formation in mice expressing wild-type hAPP. Our results support the emerging view that plaque-independent Abeta toxicity plays an important role in the development of synaptic deficits in AD and related conditions.

Transmembrane domain interactions are necessary for negative cooperativity of the insulin receptor.

Insulin binding to the human insulin receptor (HIR) is characterized by negatively cooperative site-site interactions that give rise to a curvilinear Scatchard plot. Insulin binding to recombinant secreted HIRs is linear, suggesting that interactions between the transmembrane or cytoplasmic domains of the receptor heterodimers may be responsible for the generation of negative cooperativity. To determine the domains responsible, a series of HIR cDNAs encoding C-terminal deletion mutations was constructed; HIR.delta CT, HIR.delta TK, HIR.delta TMCP-encoded deletions of the tyrosine kinase regulatory, the tyrosine kinase regulatory and catalytic, the cytoplasmic and the transmembrane and cytoplasmic domains, respectively. When expressed in COS cells, all cDNAs were processed to mature alpha- and beta- subunits. The affinity of HIR.delta CT, HIR.delta TK, and HIR.delta CP for insulin were 2- to 3-fold greater than that of wild type HIR (HIR.WT) which was 4- to 5-fold greater than that of HIR.delta TMCP. Scatchard plots of HIR.delta CT, HIR.delta TK, and HIR.delta CP, like that of HIR.WT, were curvilinear. In contrast, that of HIR.delta TMCP was linear. We conclude that constraints imposed on HIR structure by membrane insertion and/or interactions between receptor transmembrane domains are essential for the generation of negative cooperativity. Further, interactions between the C-terminal regions of the cytoplasmic domains appear to modulate affinity for insulin.

Identification and nucleotide sequence of the activator gene of the externally induced phosphoglycerate transport system of Salmonella typhimurium.

A recent study from this laboratory (G-q. Yu, D. Goldrick, H.R. Kaback and J-s. Hong, in preparation) indicates that the externally induced phosphoglycerate transport system (pgt) of Salmonella typhimurium is positively regulated by the activator gene, pgtA, and that the pgtA is localized in the SalI-PstI restriction fragment 3.0 kb from the permease gene, pgtP. In this paper, we describe the identification of the activator gene and its gene product and the determination of the complete nucleotide (nt) sequence of the activator gene as well as of a downstream gene not required for pgtP expression. The amino acid sequence of the activator based on the nt sequence shows an N-terminal signal-like sequence which is apparently not cleaved and three potential transmembrane sequences in the C-terminal half of the protein based on the hydropathy analysis.

Red plaque formation of Coxiella burnetii and reduction assay by monoclonal antibodies.

A red plaque technique for C. burnetii which utilizes primary chicken embryo cells, is described. Red plaques could be consistently detected as early as 6 days, usually 8 days post inoculation (p.i.), reflecting that C. burnetii proliferated within the phagolysosomes of host cells. Incubation with phase II monoclonal antibodies or inactivated immune sera containing phase I and phase II antibodies or phase II antibodies only, markedly reduced phase II C. burnetii red plaques. On the other hand, red plaques from phase I organisms increased several times when phase I cells were mixed with phase I monoclonal antibodies or inactivated immune sera containing phase I and phase II antibodies. By indirect red plaque reduction assay red plaque production by phase II cells could be reduced as well.

Protective immunity induced by 67 K outer membrane protein of phase I Coxiella burnetii in mice and guinea pigs.

A 67 K outer membrane protein (OMP) isolated from phase I Coxiella burnetii QiYi strain was purified with monoclonal antibodies (MoAb) coupled to CNBr-Sepharose 4B. Chemical analyses of the 67 K protein showed that it contained seventeen kinds of amino acids and no LPS. The immunogenicity and protectivity of the 67 K protein against C. burnetii was evaluated in mice and guinea pigs by in vitro lymphocyte proliferation assay, delayed-type skin test, antibody conversion rate, and immunization and challenge tests. Intraperitoneal injection of the 67 K protein resulted in antibody production against phase I and II whole cell antigens. The anti-67 K antibody conversion rate was found to be 100% in mice and guinea pigs as well. Lymphocytes were responses in vitro to specific antigen. In addition, delayed-type hypersensitivity appeared two weeks after immunization with the 67 K protein. Moreover, 100% of mice and guinea pigs inoculated with the 67 K protein were protected against a challenge with 10(3) ID50 virulent C. burnetii. In conclusion, these results demonstrate that the 67 K OMP elicits in vivo and in vitro both B cell-mediated and T cell-mediated immunity in mice and guinea pigs. Thus the 67 K protein is a candidate for an effective subunit vaccine against Q fever.

Analysis of proteins and lipopolysaccharides from Chinese isolates of Coxiella burnetii with monoclonal antibodies.

Four Coxiella burnetii isolates in China and two reference strains were compared by SDS-PAGE and immunoblotting. The SDS-PAGE profiles of whole cells and LPS of Chinese isolates Qiyi, Xinqiao, and YS-8 were found closely related to Henzerling strain, and different from the Grita strain. In immunoblot assay of LPS and proteinase K-digested whole rickettsiae minor differences were seen in polysaccharide structure among the Chinese isolates by phase I monoclonal antibody. The present results suggest that the strains reported here may be divided into three groups according to the polysaccharide structure: Xinqiao and Henzerling strains (1), YS-8 and Grita (2), and Qiyi (3).

[On the relation between substance P and physostigmine on cardiovascular control in rabbit brain].

Using an electromagnetic flowmeter technique, the cardiac output as measured by blood flow in the aortic arch was measured during intracerebroventricular injection (icv.) of Substance P (SP) and physostigmine in 47 anesthetized rabbits. Carotid artery blood pressure and heart rate were recorded. After icv of SP (20 micrograms/20 microliters) or physostigmine (60 micrograms/20 microliters), both cardiac output and mean artery pressure were increased. Pretreatment with icv. of atropine (150 micrograms/20 microliters) did not alter the effect of SP, but the effect of physostigmine was blocked by pretreatment with SP blocker (25 micrograms/20 microliters). These findings suggest that cerebral SP is involved in cholinergic mechanisms on the central control of blood pressure.

Studies on heterologous expression of Rhizobium meliloti nifA gene and oxygen sensitivity of its product.

When the R. meliloti (Rm) nifA'-lacZ fusion-carrying plasmids were introduced into the strains of Agrobacterium tumefaciens, R. trifolii and R. astragalus, beta-galactosidase activity was demonstrated. However, activity was not induced by microaerobiosis. Furthermore, R. meliloti nifA'-lacZ fusion was also not expressed in the nodule bacteroids of R. trifolii and R. astragalus. We speculate that some factor(s) important for the induction of Rm nifA presumed to be the fixLJ regulatory system would not be operative in these bacteria. Experiments using R. meliloti nifH'-lacZ/K. Pneumoniae nifH'-lacZ fusion and the constitutive Rm nifA system to test the nifA-dependent expression of nifH'-lacZ under aerobic and microaerobic conditions in E. coli were performed. The inhibition of the Rm nifA activation of nifH'-lacZ expression in the bacteria grown in the aerobic condition was shown. Assays on the Rm nifA-m RNA produced by the constitutive Rm nifA in E. coli under aerobic and microaerobic conditions with the cloned nifA as a probe for dot blot hybridization showed a marked decrease of Rm nifA mRNA when the bacteria were grown under aeration.

Evidence that the nodulation regulatory gene nodD3 of Rhizobium meliloti is transcribed from two separate promoters.

The Bgl II fragment carried in plasmid pMH903, which covers the nodD3 region of Rhizobium meliloti, has been sequenced. By using both S1 nuclease mapping and primer extension, two transcription start sites were demonstrated in the sequence. After the first transcription start site, there were two open reading frames (ORF) followed by the nodD3 coding sequence which was also preceded by the second promoter. The nodD3 gene under the first promoter mediated high, constitutive expression of nodC-lacZ fusion, and the gene under the second promoter required the product of nodD1 and alfalfa (Medicago sativa) seed exudate for the activation of fusion. Nodulation experiments showed that the nodD3 gene under either promoter was functional in eliciting nodules on alfalfa. The deletion of part of the two ORFs after the first promoter or deletion of the second promoter did not block the constitutive expression of nodC-lacZ fusion, whereas the deletion of the first promoter region or a polar insertion mutation between the two promoters did cause nodD3 to activate nodC only in the presence of the inducer. It indicates that nodD3 can be transcribed from the first promoter as well as from a separate second promoter.