Surface nanostructures on Nb-doped SrTiO3irradiated with swift heavy ions at grazing incidence.

A single crystal of SrTiO3doped with 0.5 wt% niobium (Nb-STO) was irradiated with 200 MeV Au32+ions at grazing incidence to characterize the irradiation-induced hillock chains. Exactly the same hillock chains are observed by using atomic force microscopy (AFM) and scanning electron microscopy (SEM) to study the relation between irradiation-induced change of surface topography and corresponding material property changes. As expected, multiple hillocks as high as 5-6 nm are imaged by AFM observation in tapping mode. It is also found that the regions in between the adjacent hillocks are not depressed, and in many cases they are slightly elevated. Line-like contrasts along the ion paths are found in both AFM phase images and SEM images, indicating the formation of continuous ion tracks in addition to multiple hillocks. Validity of preexisting models for explaining the hillock chain formation is discussed based on the present results. In order to obtain new insights related to the ion track formation, cross-sectional transmission electron microscopy (TEM) observation was performed. The ion tracks in the near-surface region are found to be relatively large, whereas buried ion tracks in the deeper region are relatively small. The results suggest that recrystallization plays an important role in the formation of small ion tracks in the deep region, whereas formation of large ion tracks in the near-surface region is likely due to the absence of recrystallization. TEM images also show shape deformation of ion tracks in the near-surface region, suggesting that material transport towards the surface is the reason for the absence of recrystallization.

Comparison of osseous healing after sagittal split ramus osteotomy and intraoral vertical ramus osteotomy.

The sagittal split ramus osteotomy (SSRO) is generally associated with greater postoperative stability than the intraoral vertical ramus osteotomy (IVRO); however, it entails a risk of inferior alveolar nerve damage. In contrast, IVRO has the disadvantages of slow postoperative osseous healing and projection of the antegonial notch, but inferior alveolar nerve damage is believed to be less likely. The purposes of this study were to compare the osseous healing processes associated with SSRO and IVRO and to investigate changes in mandibular width after IVRO in 29 patients undergoing mandibular setback. On computed tomography images, osseous healing was similar in patients undergoing SSRO and IVRO at 1year after surgery. Projection of the antegonial notch occurred after IVRO, but returned to the preoperative state within 1year. The results of the study indicate that IVRO is equivalent to SSRO with regard to both bone healing and morphological recovery of the mandible.

Mutant botrocetin-2 inhibits von Willebrand factor-induced platelet agglutination.

Essentials Botrocetin-2 (Bot2) binds to von Willebrand factor (VWF) and induces platelet agglutination. We identified Bot2 residues that are required for binding to VWF and glycoprotein (GP) Ib. We produced a mutant Bot2 that binds to VWF but inhibits platelet agglutination. Mutant Bot2 could be used as a potential anti-thrombotic reagent to block VWF-GPIb interaction. SUMMARY: Background Botrocetin-2 (Bot2) is a botrocetin-like protein composed of α and ß subunits that have been cloned from the snake Bothrops jararaca. Bot2 binds specifically to von Willebrand factor (VWF), and the complex induces glycoprotein (GP) Ib-dependent platelet agglutination. Objectives To exploit Bot2's VWF-binding capacity in order to attempt to create a mutant Bot2 that binds to VWF but inhibits platelet agglutination. Methods and Results Several point mutations were introduced into Bot2 cDNA, and the recombinant protein (recombinant Bot2 [rBot2]) was purified on an anti-botrocetin column. The mutant rBot2 with either Ala at Asp70 in the ß subunit (Aspß70Ala), or Argß115Ala and Lysß117Ala, showed reduced platelet agglutination-inducing activity. rBot2 with Aspß70Ala showed little binding activity towards immobilized VWF on an ELISA plate, whereas rBot2 with Argß115Ala/Lysß117Ala showed reduced binding activity towards GPIb (glycocalicin) after forming a complex with VWF. rBot2 point-mutated to oppositely charged Glu at both Argß115 and Lysß117 showed normal binding activity towards VWF but no platelet-agglutinating activity. Furthermore, this doubly mutated protein inhibited ristocetin-induced or high shear stress-induced platelet aggregation, and restrained thrombus formation under flow conditions. Conclusions Asp70 in the ß subunit of botrocetin is important for VWF binding, and Arg115 and Lys117 in the ß subunit are essential for interaction with GPIb. Doubly mutated rBot2, with Argß115Glu and Lysß117Glu, repels GPIb and might have potential as an antithrombotic reagent that specifically blocks VWF function. This is the first report on an artificial botrocetin that can inhibit the VWF-GPIb interaction.

Quantum-mechanical approach to predissociation of water dimers in the vibrational adiabatic representation: Importance of channel interactions.

The results of application of the quantum-mechanical adiabatic theory to vibrational predissociation (VPD) of water dimers, (H2O)2 and (D2O)2, are presented. We consider the VPD processes including the totally symmetric OH mode of the dimer and the bending mode of the fragment. The VPD in the adiabatic representation is induced by breakdown of the vibrational adiabatic approximation, and two types of nonadiabatic coupling matrix elements are involved: one provides the VPD induced by the low-frequency dissociation mode and the other provides the VPD through channel interactions induced by the low-frequency modes. The VPD rate constants were calculated using the Fermi golden rule expression. A closed form for the nonadiabatic transition matrix element between the discrete and continuum states was derived in the Morse potential model. All of the parameters used were obtained from the potential surfaces of the water dimers, which were calculated by the density functional theory procedures. The VPD rate constants for the two processes were calculated in the non-Condon scheme beyond the so-called Condon approximation. The channel interactions in and between the initial and final states were taken into account, and those are found to increase the VPD rates by 3(1) orders of magnitude for the VPD processes in (H2O)2 ((D2O)2). The fraction of the bending-excited donor fragments is larger than that of the bending-excited acceptor fragments. The results obtained by quantum-mechanical approach are compared with both experimental and quasi-classical trajectory calculation results.

Outdoor physical activity and its relation with self-reported health in Japanese children: results from the Toyama birth cohort study.

BACKGROUND: Few studies have examined trends in engagement in outdoor physical activity as children grow and whether changes in physical activity at different ages affect children's health. This study determined the preference for and frequency of physical activity among Japanese children from ages 6 to 12 years and investigated the effect of physical activity and of change in physical activity on children's self-reported health. METHODS: Data were from the prospective, longitudinal Toyama Birth Cohort Study, a total of 5238 children were followed at their age of 12 years. Preference for and frequency of outdoor physical activity were from the self-administered questionnaire. Self-reported health was from the Japanese version of Dartmouth Primary Care Co-operative project charts. RESULTS: Reporting liking and participating in outdoor physical activity at both ages 6 and 12 years were associated with higher likelihood of good self-reported health (Odds ratio 1.24 [95% CI: 1.03-1.50] for liking activity and OR = 1.27[1.08, 1.50] for participating in activity) compared with those who did not like or participate in this at only one or at neither age, after adjustment for lifestyle factors and body pain. The adjusted OR was 1.23 (95% CI: 0.97-1.56) for girls whose preference for liking outdoor physical activity was not changed at both ages compared with those whose preference changed. The OR was 1.47 (95% CI: 1.14-1.89) for boys who persisted in participating in the outdoor physical activity than those who did not persist. CONCLUSIONS: There is an association between a persistent expression of liking outdoor physical activity and self- reported health.

Identification of N-linked glycosylation and putative O-fucosylation, C-mannosylation sites in plasma derived ADAMTS13.

BACKGROUND: Acquired deficiency of ADAMTS13 causes a rare and life-threatening disorder called thrombotic thrombocytopenic purpura (TTP). Several studies have shown that aberrant glycosylation can play an important role in the pathogenesis of autoimmune diseases.N-linked glycosylation and putative O-fucosylation sites have been predicted or identified in recombinant ADAMTS13. However, it is not known which of these sites are glycosylated in plasma derived ADAMTS13. OBJECTIVES: Here we investigated the presence of putative O-fucosylation, C-mannosylation and N-linked glycosylation sites on plasma derived ADAMTS13. METHODS/RESULTS: Sites of N-linked glycosylation were determined by the use of peptide N-glycosidase-F (PNGase F), which removes the entire carbohydrate from the side chain of asparagines. Nine of the 10 predicted N-linked glycosylation sites were identified in or near the metalloproteinase,spacer, thrombospondin type 1 repeat (TSR1) and the CUB domain of plasma ADAMTS13. Moreover, six putative O-fucosylated sites were identified in the TSR domains of plasma ADAMTS13 by performing searches of the tandem mass spectrometry (MS/MS) data for loss of hexose (162 Da), deoxyhexose (146 Da), or hexose deoxyhexose(308 Da). The use of electron transfer dissociation (ETD) allowed for unambiguous identification of the modified sites. In addition to putative O-fucosylation and N-linked glycosylation, two putative C-mannosylation sites were identified within the TSR1 and TSR4 domains of ADAMTS13. CONCLUSIONS: Our data identify several glycosylation sites on plasma derived ADAMTS13. We anticipate that our findings may be relevant for the initiation of autoimmune reactivity against ADAMTS13 in patients with acquired TTP.

Effect of ADAMTS-13 on cerebrovascular microthrombosis and neuronal injury after experimental subarachnoid hemorrhage.

BACKGROUND: Microthrombosis and reactive inflammation contribute to neuronal injury after subarachnoid hemorrhage (SAH). ADAMTS-13 cleaves von Willebrand factor multimers, and inhibits thrombus formation and, seemingly, inflammatory reactions. OBJECTIVE: To investigate the effect of ADAMTS-13 in experimental SAH. METHODS: A total of 100 male C57/BL6 mice were randomly assigned to four groups: sham (n = 15), SAH (n = 27), vehicle (n = 25), and ADAMTS-13 (n = 23; 100 µL per 10 g of body weight of 100 µg of ADAMTS-13 per 1 mL of 0.9% NaCl; 20 min after SAH). Neurologic performance was assessed on days 1 and 2 after SAH. Animals were killed on day 2. The amounts of subarachnoid blood, microthrombi, apoptosis and degenerative neurons were compared. The degree of neuronal inflammation and vasospasm was also compared. In five mice each (SAH and ADAMTS-13 groups), bleeding time was assessed 2 h after SAH. RESULTS: Systemic administration of ADAMTS-13 achieved significant amelioration of microthrombosis and improvement in neurologic performance. ADAMTS-13 reduced the amount of apoptotic and degenerative neurons. A tendency for decreased neuronal inflammation was observed. ADAMTS-13 did not show any significant effect on vasospasm. The degree of systemic inflammation was not changed by ADAMTS-13 administration. ADAMTS-13 neither increased the amount of subarachnoid blood nor prolonged the bleeding time. CONCLUSIONS: ADAMTS-13 may reduce neuronal injury after SAH by reducing microthrombosis formation and neuronal inflammation, thereby providing a new option for mitigating the severity of neuronal injury after SAH.

Non-Markovian response of ultrafast coherent electronic ring currents in chiral aromatic molecules in a condensed phase.

Results of a theoretical study on non-Markov response for femtosecond laser-driven coherent ring currents in chiral aromatic molecules embedded in a condensed phase are presented. Coherent ring currents are generated by coherent excitation of a pair of quasi-degenerated π-electronic excited states. The coherent electronic dynamical behaviors are strongly influenced by interactions between the electronic system and phonon bath in a condensed phase. Here, the bath correlation time is not instantaneous but should be taken to be a finite time in ultrashort time-resolved experiments. In such a case, Markov approximation breaks down. A hierarchical master equation approach for an improved semiclassical Drude dissipation model was adopted to examine the non-Markov effects on ultrafast coherent electronic ring currents of (P)-2,2'-biphenol in a condensed phase. Time evolution of the coherent ring current derived in the hierarchical master equation approach was calculated and compared with those in the Drude model in the Markov approximation and in the static limit. The results show how non-Markovian behaviors in quantum beat signals of ring currents depend on the Drude bath damping constant. Effects of temperatures on ultrafast coherent electronic ring currents are also clarified.

ADAMTS13 activity and genetic mutations in Japan.

Thrombotic thrombocytopenic purpura (TTP), a life threatening disease, can be induced by congenital or acquired deficiency of plasma metalloprotease ADAMTS13. Since the publication of the first genetic analysis in patients with congenital ADAMTS13 deficiency in 2001, more than 100 genetic defects in the ADAMTS13 gene have been reported worldwide. Genetic analysis in patients with ADAMTS13 deficiency has greatly contributed to the understanding of the etiology of TTP. A rapid and quantitative assay method for the plasma ADAMTS13 activity was developed recently in 2005 and opened a new area of TTP research - namely genetic research using a general population to evaluate age and gender differences of ADAMTS13 activity as well as phenotype - genotype correlations of genetic polymorphisms and estimation of a homozygote or a compound heterozygote ADAMTS13 deficiencies. The Japanese general population study included 3616 individuals with an age between 30 - 80 years confirming other studies that while ADAMTS13 activity decreased with age, VWF antigen increased and VWF antigen levels are lowest in blood group O indviduals, whereas ADAMTS13 activity levels were not associated with the AB0 blood group. 25 polymorphisms with a minor allele frequency of more than 0.01 were found, among them 6 missense mutations and 19 synonymous mutations, except P475S missense polymorphisms that was only idenitified in an East Asian population, characterized by reduced ADAMTS13 activity. Prevalence of congenital ADAMTS13 deficiency in the Japanese population was estimated about one individual in 1.1 x 106 to be homozygote or compound heterozygote for ADAMTS13 deficiency. So far more than 40 mutations in Japanese congenital TTP patients were found, but R193W, Q449*, C754Afs*24 (c.2259delA) and C908Y were identified in more than four patients suggesting the precipitaion of these mutations in the Japanese population.

Hereditary thrombotic thrombocytopenic purpura and the hereditary TTP registry.

Hereditary thrombotic thrombocytopenic purpura, Upshaw-Schulman syndrome, ADAMTS13 Hereditary thrombotic thrombocytopenic purpura (TTP), also known as Upshaw-Schulman syndrome, is a rare recessively inherited disease. Underlying is a severe constitutional deficiency of the von Willebrand factor-cleaving protease, ADAMTS13, due to compound heterozygous or homozygous mutations in the ADAMTS13 gene. The clinical picture is variable and more and more patients with an adult-onset are diagnosed. In the majority of countries the only available treatment is plasma, which when administered regularly can efficiently prevent acute disease bouts. The decision to initiate regular prophylaxis is often not easy, as evidence based guidelines and long term outcome data are lacking. Through the hereditary TTP registry (www.ttpregistry.net, ClinicalTrials.gov identifier: NCT01257269), which was initiated in 2006 and is open to all patients diagnosed with Upshaw-Schulman syndrome and their family members, we aim to gain further information and insights into this rare disease, which eventually will help to improve clinical management of affected patients.

Coherent π-electron dynamics of (P)-2,2'-biphenol induced by ultrashort linearly polarized UV pulses: angular momentum and ring current.

The results of a theoretical investigation of coherent π-electron dynamics for nonplanar (P)-2,2'-biphenol induced by ultrashort linearly polarized UV pulses are presented. Expressions for the time-dependent coherent angular momentum and ring current are derived by using the density matrix method. The time dependence of these coherences is determined by the off-diagonal density matrix element, which can be obtained by solving the coupled equations of motion of the electronic-state density matrix. Dephasing effects on coherent angular momentum and ring current are taken into account within the Markov approximation. The magnitudes of the electronic angular momentum and current are expressed as the sum of expectation values of the corresponding operators in the two phenol rings (L and R rings). Here, L (R) denotes the phenol ring in the left (right)-hand side of (P)-2,2'-biphenol. We define the bond current between the nearest neighbor carbon atoms Ci and Cj as an electric current through a half plane perpendicular to the Ci-Cj bond. The bond current can be expressed in terms of the inter-atomic bond current. The inter-atomic bond current (bond current) depends on the position of the half plane on the bond and has the maximum value at the center. The coherent ring current in each ring is defined by averaging over the bond currents. Since (P)-2,2'-biphenol is nonplanar, the resultant angular momentum is not one-dimensional. Simulations of the time-dependent coherent angular momentum and ring current of (P)-2,2'-biphenol excited by ultrashort linearly polarized UV pulses are carried out using the molecular parameters obtained by the time-dependent density functional theory (TD-DFT) method. Oscillatory behaviors in the time-dependent angular momentum (ring current), which can be called angular momentum (ring current) quantum beats, are classified by the symmetry of the coherent state, symmetric or antisymmetric. The bond current of the bridge bond linking the L and R rings is zero for the symmetric coherent state, while it is nonzero for the antisymmetric coherent state. The magnitudes of ring current and ring current-induced magnetic field are also evaluated, and their possibility as a control parameter in ultrafast switching devices is discussed. The present results give a detailed description of the theoretical treatment reported in our previous paper [H. Mineo, M. Yamaki, Y. Teranish, M. Hayashi, S. H. Lin, and Y. Fujimura, J. Am. Chem. Soc. 134, 14279 (2012)].

Natural history of Upshaw-Schulman syndrome based on ADAMTS13 gene analysis in Japan.

Upshaw-Schulman syndrome (USS) is an extremely rare hereditary deficiency of ADAMTS13 activity, termed congenital TTP. The clinical signs are usually mild during childhood, often with isolated thrombocytopenia. But their symptoms become more evident when patients have infections or get pregnant. We identified 43 USS-patients in Japan, who ranged in age from early childhood to 79 years of age. Analysing the natural history of these USS patients based on ADAMTS13 gene mutations may help characterise their clinical phenotypes. Severe neonatal jaundice that requires exchange blood transfusion, a hallmark of USS, was found in 18 of 43 patients (42%). During childhood, 25 of 43 patients were correctly diagnosed with USS without gender disparity. These 25 patients were categorised as having 'the early-onset phenotype'. Between 15 and 45 years of age, 15 were correctly diagnosed, and, interestingly, they were all female. The remaining three patients were male and were diagnosed when they were older than 45 years of age, suggesting that they were 'the late-onset phenotype'. Two of these three males developed sudden overt TTP when they were 55 and 63 years old, respectively. These two men had two different homozygous ADAMTS13 gene mutations, p.R193W/p.R193W and p.C1024R/p.C1024R, respectively. Both of which were not discovered in the US or Western countries. In vitro expression studies showed that these two proteins were consistently secreted into the culture medium but to a lesser extent and with reduced activity compared to the wild-type protein. Our results indicate that 'the late-onset phenotype' of USS is formed with ethnic specificity.

Density functional theory study of conformation-dependent properties of neutral and radical cationic L-tyrosine and L-tryptophan.

Conformation-dependent properties of L-tyrosine and L-tryptophan in neutral and radical cations were studied by using the density functional theory (DFT) with a new density functional M05-2X. The results are compared with those obtained by using the conventional DFT (B3LYP). Results obtained by both types of DFT were in qualitative accord, including the existence of two conformational subgroups and their subgroup-dependent adiabatic ionization energy and hydrogen bonding. On the other hand, quantitative differences were found between the two DFT methods as well: the M05-2X method successfully reproduced experimental adiabatic ionization energy, whereas the B3LYP functional consistently yielded significantly lower values by 0.2-0.3 eV. More importantly, natural bond orbital (NBO) analysis for cationic conformers showed that all conformers of L-tyrosine and L-tryptophan undergo charge localization upon ionization regardless of the presence of intramolecular hydrogen bonding, unlike the case of L-phenylalanine that was treated earlier by other studies. Different degrees of charge localization among all three aromatic amino acids are explained by employing a simple model in which the aromatic amino acid is assumed to consist of two submoieties of distinct cationic core: the backbone and aromatic side chain. The difference in adiabatic ionization energy between these two submoieties is found to govern the degree of charge localization.

Investigation of conformation-dependent properties of L-phenylalanine in neutral and radical cations by using a density functional taking into account noncovalent interactions.

Conformation-dependent properties of l-phenylalanine in neutral and radical cations have been studied by using density functional theory (DFT) with a new density functional M05-2X, which is applicable to molecular systems with nonconvalent interactions. Adiabatic and vertical ionization energies and charge distributions in the cationic conformers in addition to optimized geometrical structures for both the neutral and the cationic conformers were evaluated. These results were compared with DFT (B3LYP) results. The M05-2X results can explain the correspondence between the observed and predicted conformers without ambiguity. The possibility of conformerization of neutral conformers is indicated from the results of IRC (intrinsic reaction coordinate) profiles.

Bmi1 is a MYCN target gene that regulates tumorigenesis through repression of KIF1Bbeta and TSLC1 in neuroblastoma.

Recent advances in neuroblastoma (NB) research addressed that epigenetic alterations such as hypermethylation of promoter sequences, with consequent silencing of tumor-suppressor genes, can have significant roles in the tumorigenesis of NB. However, the exact role of epigenetic alterations, except for DNA hypermethylation, remains to be elucidated in NB research. In this paper, we clarified the direct binding of MYCN to Bmi1 promoter and upregulation of Bmi1 transcription by MYCN. Mutation introduction into an MYCN binding site in the Bmi1 promoter suggests that MYCN has more important roles in the transcription of Bmi1 than E2F-related Bmi1 regulation. A correlation between MYCN and polycomb protein Bmi1 expression was observed in primary NB tumors. Expression of Bmi1 resulted in the acceleration of proliferation and colony formation in NB cells. Bmi1-related inhibition of NB cell differentiation was confirmed by neurite extension assay and analysis of differentiation marker molecules. Intriguingly, the above-mentioned Bmi1-related regulation of the NB cell phenotype seems not to be mediated only by p14ARF/p16INK4a in NB cells. Expression profiling analysis using a tumor-specific cDNA microarray addressed the Bmi1-dependent repression of KIF1Bbeta and TSLC1, which have important roles in predicting the prognosis of NB. Chromatin immunoprecipitation assay showed that KIF1Bbeta and TSLC1 are direct targets of Bmi1 in NB cells. These findings suggest that MYCN induces Bmi1 expression, resulting in the repression of tumor suppressors through Polycomb group gene-mediated epigenetic chromosome modification. NB cell proliferation and differentiation seem to be partially dependent on the MYCN/Bmi1/tumor-suppressor pathways.

Functional characterization of CYP3A4.16: catalytic activities toward midazolam and carbamazepine.

1. To assess the substrate-dependent effects of the low-activity allele of human CYP3A4, CYP3A4*16 (Thr185Ser), a recombinant wild-type (CYP3A4.1) or variant (CYP3A4.16) protein was co-expressed with human NADPH-P450 reductase in Sf21 insect cells using a baculovirus-insect cell system. 2. The holo-CYP3A4 protein level of CYP3A4.16 in insect microsomes was slightly higher than that of CYP3A4.1, while no difference in total (apo- and holo-) CYP3A4 protein levels was observed between them. 3. When midazolam was used as a substrate, K(m) and V(max) for 1'-hydroxylation in CYP3A4.16 were significantly higher and lower, respectively, than those in the wild-type, resulting in a 50% decrease in intrinsic clearance (V(max)/K(m)) of the variant. In contrast, intrinsic clearance for 4-hydroxylation of the variant was decreased by 30% due to a significant increase in K(m) without a difference in V(max). 4. Both the wild-type and variant exhibited sigmoidal kinetic profiles for carbamazepine 10,11-epoxide formation. When the modified two-site equation was applied for the analysis of kinetic parameters, K(m2) and V(max2) of CYP3A4.16 were approximately two times higher and lower than those of the wild-type, resulting in a 74% decrease in intrinsic clearance. 5. These results demonstrated that CYP3A4.16 shows the substrate-dependent altered kinetics compared with CYP3A4.1.

Second international collaborative study evaluating performance characteristics of methods measuring the von Willebrand factor cleaving protease (ADAMTS-13).

BACKGROUND: Over the last 4 years ADAMTS-13 measurement underwent dramatic progress with newer and simpler methods. AIMS: Blind evaluation of newer methods for their performance characteristics. DESIGN: The literature was searched for new methods and the authors invited to join the evaluation. Participants were provided with a set of 60 coded frozen plasmas that were prepared centrally by dilutions of one ADAMTS-13-deficient plasma (arbitrarily set at 0%) into one normal-pooled plasma (set at 100%). There were six different test plasmas ranging from 100% to 0%. Each plasma was tested 'blind' 10 times by each method and results expressed as percentage vs. the local and the common standard provided by the organizer. RESULTS: There were eight functional and three antigen assays. Linearity of observed-vs.-expected ADAMTS-13 levels assessed as r2 ranged from 0.931 to 0.998. Between-run reproducibility expressed as the (mean) CV for repeated measurements was below 10% for three methods, 10-15% for five methods and up to 20% for the remaining three. F-values (analysis of variance) calculated to assess the capacity to distinguish between ADAMTS-13 levels (the higher the F-value, the better the capacity) ranged from 3965 to 137. Between-method variability (CV) amounted to 24.8% when calculated vs. the local and to 20.5% when calculated vs. the common standard. Comparative analysis showed that functional assays employing modified von Willebrand factor peptides as substrate for ADAMTS-13 offer the best performance characteristics. CONCLUSIONS: New assays for ADAMTS-13 have the potential to make the investigation/management of patients with thrombotic microangiopathies much easier than in the past.

An anti-c-Fms antibody inhibits orthodontic tooth movement.

Orthodontic force induces osteoclastogenesis in vivo. It has recently been reported that administration of an antibody against the macrophage-colony-stimulating factor (M-CSF) receptor c-Fms blocks osteoclastogenesis and bone erosion induced by tumor necrosis factor-alpha (TNF-alpha) administration. This study aimed to examine the effect of an anti-c-Fms antibody on mechanical loading-induced osteoclastogenesis and osteolysis in an orthodontic tooth movement model in mice. Using TNF receptor 1- and 2-deficient mice, we showed that orthodontic tooth movement was mediated by TNF-alpha. We injected anti-c-Fms antibody daily into a local site, for 12 days, during mechanical loading. The anti-c-Fms antibody significantly inhibited orthodontic tooth movement, markedly reduced the number of osteoclasts in vivo, and inhibited TNF-alpha-induced osteoclastogenesis in vitro. These findings suggest that M-CSF plays an important role in mechanical loading-induced osteoclastogenesis and bone resorption during orthodontic tooth movement mediated by TNF-alpha.