Improving

Improving Navitoclax training, increasing awareness and exploring new approaches to obtaining the information are required.”
“Simulated sunlight irradiation causing degradation of amidosulfuron, a pyrimidinylsulfonylurea herbicide, has been investigated in aqueous solution. The main degradation products were followed up by ultrahigh-pressure liquid chromatography

with a UV detector (UHPLC-UV) and identified by combining ultrahight-pressure liquid chromatography-mass spectrometry (UHPLC-MS) and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). On the basis of the retrosynthetic analysis, the most identified degradation products were mainly due to the losses of methylsulfamic acid (CH5NO3S), sulfocarbamic acid (CH3NO5S), carbamic acid (CH3NO2), methyl(methylsulfonyl)sulfamic acid (C2H7NO5S2), N-methylmethanesulfonamide (C2H7NO2S), and sulfonic acid (H2SO4) molecules. Accordingly, O and S-demethylation as well as hydroxylation processes were also observed. Sum formulas of the main degradation products were assigned, and a mechanical pathway is proposed.”
“Contaminant exposure can vary between species but primary causes of it are often unclear. In order to estimate heavy metal

intake SHP099 of two sympatric passerines – Ficedula hypoleuca Pall. and Parus ater L. – we studied nestling diet and metal concentrations in prey invertebrates, near the Middle Ural copper smelter and in an unpolluted area. Diet of P. ater contained more Cu, Cd and Zn compared to E hypoleuca and the same amount of Pb. Contribution of different prey taxa to bird metal intake was not equal to their dietary proportion. Proportion of Cu, Zn, Pb and Cd provided to birds by spiders and molluscs, as well as Cd and Pb provided by ants and imagoes Diptera, exceeded their dietary fraction by several times. In contrast, the contribution of Lepidoptera and sawfly larvae to bird metal intake was less than their dietary proportion. Pollution-related

changes in the diet modified bird contaminant exposure selleck products along with pollutant concentrations in preys. (C) 2013 Elsevier Inc. All rights reserved.”
“Background and purpose: Permanent right ventricular apical pacing can result in heart failure due to ventricular mechanical dyssynchrony. The purpose of the study was to define differences in left ventricular dyssynchrony between high septet pacing and apical pacing using tissue Doppler imaging (TDI) and two-dimensional (2D) speckle-tracking echocardiography (STE).\n\nMethods: The subjects were 60 patients with normal left ventricular systolic function who underwent implantation of a permanent pacemaker. Patients were divided into two groups with high septet pacing (n=36) and conventional right apical pacing (n=24). Left ventricular dyssynchrony was measured using TDI and 2D-STE.

IMRT plans generated with the 160-MLC were found to significantly

IMRT plans generated with the 160-MLC were found to significantly reduce the total delivered monitor units by up to 14.7% and the number of segments by as much as 10.7% compared to the 58-MLC. The average delivery time for the direct aperture optimized (DAO) IMRT plans generated with the 160-MLC click here was approximately 5 minutes. Overall, compared to the 58-MLC, the new 160-MLC was found to improve dosimetric

conformity and IMRT delivery efficiency.”
“Foot-and-mouth disease, the most devastating and highly contagious viral disease of cloven-footed animals, causes significant financial losses either due to deaths of young animals, loss of milk, meat and drastic fall in productive performances or serious limitations on development of livestock industry due to restrictions on international trade. In spite of the considerable information accumulated in the last years on the disease, it still affects extensive areas of the world and ranks as first in the list ‘A’ of infectious diseases of animals according to the Office International des Epizooties, Perris, France. In this review, we have to summarize the state of knowledge in basic and applied areas of FMD research with emphasis on epidemiology and diagnosis to make progress in controlling the disease

from the livestock.”
“Low-contrast images, such as color microscopic images of unstained histological specimens, are composed of objects with highly correlated spectral profiles. Such images are very hard to segment. Here, we present a method that nonlinearly maps low-contrast color image into an image with an increased number of non-physical channels and a decreased https://www.selleckchem.com/products/VX-680(MK-0457).html correlation between spectral profiles. The method is a proof-of-concept validated on the unsupervised segmentation of color images of unstained

specimens, in which case the tissue components appear colorless when viewed under the light microscope. Specimens of human hepatocellular carcinoma, human liver with metastasis from colon and gastric cancer and mouse fatty liver were used for validation. The average correlation between the spectral profiles of the tissue components was greater than 0.9985, and the worst case correlation was greater than 0.9997. The proposed method can potentially MK-2206 supplier be applied to the segmentation of low-contrast multichannel images with high spatial resolution that arise in other imaging modalities.”
“We have investigated the impacts of 63 different low-molecular-weight compounds, most of them plant derived, on the in vitro expression of two antifungal biosynthetic genes by the plant-protecting rhizobacterium Pseudomonas fluorescens CHA0. The majority of the compounds tested affected the expression of one or both antifungal genes. This suggests that biocontrol activity in plant-beneficial pseudomonads is modulated by plant-bacterium signaling.”
“Myxococcus fulvus HW-1, a salt-tolerant bacterial strain, which was isolated from a coastal environment, changes its behavior with different salinities.

(c) 2013 Elsevier Inc All rights reserved “
“Studies of the

(c) 2013 Elsevier Inc. All rights reserved.”
“Studies of the possibility of regulating the regenerative and reparative processes in pathologically modified tissues are reviewed. A ready cell system providing the realization of reparative and regenerative processes in all organs (cell sources of regeneration) exists in all organisms. The authors

suggest that active bioregulators presented in this paper are involved in the mechanisms of tissue regeneration by modulating the cell sources of regeneration.”
“A rearrangement of genera and subgenera in the water mite family Mideopsidae is proposed, resulting in the following selleck screening library changes: Mideopsellinae Lundblad, 1937 and Phreatomideopsinae Schwoerbel, 1986 are synonymized with Mideopsidae Koenike, 1910; Djeboa K. Viets, 1911, Mideopsides Lundblad, 1943, Neoxystonotus Lundblad, 1927, Octomideopsis K. Viets, 1931 and Xystonotus Wolcott, 1900 are redefined and proposed as distinct genera. A global key for the genera of the family is given.\n\nNew records of water mites of the genus Djeboa K. Viets, 1911, Xystonotus Wolcott, 1900 and Mideopsellides K.O. Viets, 1962 (Acari: Hydrachnidia, Mideopsidae) from the Afrotropical region are presented. Twenty species new to science are described, i.e., https://www.selleckchem.com/products/blasticidin-s-hcl.html Djeboa amendano (Madagascar), D. amethystica (Madagascar), D. angulipalpis (Madagascar), D. coelestinica

(Madagascar), D. crocodilorum (South Africa), D. curtipalpis (Ghana), Djeboa depressa(Cote d’Ivoire), D. dinosaurophila (South Africa), D. elephantina (Cote d’Ivoire), D. ghanaensis (Ghana), D. gledhilli (Cote d’Ivoire, Ghana), D. globulipalpis (South Africa, Ghana), D. granatica (Madagascar),

D. mandena selleck chemicals llc (Madagascar), D. maromandia (Madagascar), D. nzia (Cote d’Ivoire), D. turmalinica (Madagascar), D. vanilla (Madagascar), D. wondergemi (Ghana) and Xystonotus madagascariensis (Madagascar); a first description of the male is given for Djeboa bimaculata (Cook, 1966). A key for all species of the Djeboa is presented.”
“Calcium carbonate mineralization is significantly influenced by organic matrices in vivo. The effect mainly relies on functional groups in proteins. In order to study the influence of functional groups on calcium carbonate mineralization, -OH, -NH(2) and -COOH groups were grafted onto single crystal silicon chips, and such modified chips were used as substrates in in vitro mineralization experiments. An x-ray photoelectron spectroscopy (XPS) test was conducted to examine the grafting efficiency, and the three groups were successfully grafted. Calcium carbonate mineralization on a modified silicon substrate was examined by a scanning electron microscope (SEM) and x-ray diffraction (XRD), and the results showed that the effects of -OH, -NH2 and -COOH groups were quite different.

Evidence for predictive validity was based on the results of mult

Evidence for predictive validity was based on the results of multilevel regression models of the readiness measures in predicting frequency of marijuana use, symptoms, and problems at 6 months from the initial readiness assessment and then in predicting marijuana

use, symptoms, and problems at MGCD0103 ic50 12 months from the readiness assessment at 6 months. Results: The results showed evidence for good concurrent and predictive validity for the ruler, the staging algorithm, and Taking Steps but poor evidence for the validity of Recognition. The ruler emerged as the measure with the most clinical utility when brevity and ease of administration are taken into account. Conclusions: Research and clinical implications of the findings are discussed. (J. Stud. Alcohol Drugs, 72, 592-601, 2011)”
“To develop RAF/VEGFR2 inhibitors that

bind to the inactive DFG-out conformation, we conducted structure-based drug design using the X-ray cocrystal structures PF299 of BRAF, starting from an imidazo[1,2-b]pyridazine derivative. We designed various [5,6]-fused bicyclic scaffolds (ring A, 1-6) possessing an anilide group that forms two hydrogen bond interactions with Cys532. Stabilizing the planarity of this anilide and the nitrogen atom on the six-membered ring of the scaffold was critical for enhancing BRAF inhibition. The selected [1,3]thiazolo[5,4-b]pyridine derivative 6d showed potent inhibitory activity in both BRAF and VEGFR2. Solid dispersion formulation of 6d (6d-SD) maximized its oral absorption in rats and showed significant

suppression of ERK1/2 phosphorylation in an A375 melanoma xenograft model in rats by single administration. Tumor regression (T/C = -7.0%) in twice-daily BMS-777607 repetitive studies at a dose of 50 mg/kg in rats confirmed that 6d is a promising RAF/VEGFR2 inhibitor showing potent anticancer activity.”
“Objective: Aortic pulse wave velocity (aPWV) is a gold standard noninvasive marker of arterial stiffness. aPWV is usually obtained as carotid-femoral pulse wave velocity by measurements on the common carotid artery and the femoral artery. The carotid arteries branch slightly differently from the aorta towards the right and left side of the neck. Theoretically, using the right or left carotid artery could influence aPWV results and there are no clear guidelines to support the choice of side. The aim of this study was to investigate whether aPWV results depend on right or left side carotid artery measurements in a group of healthy individuals.\n\nMethods and results: Two different observers examined 50 individuals without known cardiovascular disease between 23 and 66 years of age. The measurements were performed with the SphygmoCor equipment using both right and left carotid arteries.

In particular, the formula correctly predicts the elevation of lo

In particular, the formula correctly predicts the elevation of low-and high-frequency variants and is significantly more accurate than previously derived formulas for intermediate frequency variants.”
“Mesoporous yolk-shell structure Bi2MoO6 (BMO-YS) microspheres were successfully synthesized via a facile solvothermal route in Bi2MoO6 precursor solution. The morphology, structure and photocatalytic performance of

the BMO-YS in the degradation of Rhodamine B (RhB) were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, nitrogen adsorption desorption, UV-vis absorption spectroscopy and electrochemical impedance spectra, STA-9090 in vitro respectively. The as-prepared BMO-YS mainly consists of microspheres with

diameters of about 1.5 mu m. The photocatalytic studies reveal that the BMO-YS not only exhibits optimum photocatalytic performance, which may be attributed to the excellent charge separation characteristics and the enhanced light absorption offered by its unique yolk-shell structure, but also possesses excellent recyclability for photocatalysis. (C) 2015 Elsevier Ltd and Techna Group S.r.l. All rights reserved.”
“Interaction between the iron transporter protein transferrin (Tf) and its receptor at the cell surface is fundamental for most living organisms. Tf receptor (TfR) binds iron-loaded Tf (holo-Tf) and transports

it to endosomes, where acidic pH favors iron release. Iron-free Tf (apo-Tf) is then brought back to the cell surface and dissociates from TfR. Here we investigated selleck products the Tf-TfR interaction at the single-molecule level under different conditions encountered during the Tf cycle. An atomic force microscope tip functionalized with holo-Tf or apo-Tf this website was used to probe TfR. We tested both purified TfR anchored to a mica substrate and in situ TfR at the surface of living cells. Dynamic force measurements showed similar results for TfR on mica or at the cell surface but revealed striking differences between holo-Tf-TfR and apo-Tf-TfR interactions. First, the forces necessary to unbind holo-Tf and TfR are always stronger compared to the apo-Tf-TfR interaction. Second, dissociation of holo-Tf-TfR complex involves overcoming two energy barriers, whereas the apo-Tf-TfR unbinding pathway comprises only one energy barrier. These results agree with a model that proposes differences in the contact points between holo-Tf-TfR and apo-Tf-TfR interactions.”
“Human immunodeficiency virus (HIV) is the primary etiologic agent responsible for the AIDS pandemic. In this work, we used a chimeric recombinant protein strategy to test the possibility of irreversibly destroying the HIV-1 virion using an agent that simultaneously binds the Env protein and viral membrane.

They further appear to experience greater invertor moments at the

They further appear to experience greater invertor moments at their feet, decreased abduction and flexion velocities at their hips and to reach maximum hip flexion angles earlier than healthy controls. Maximum normalised braking forces seem to be decreased in these athletes. The literature is inconclusive with regards to muscle strength deficits in runners with a history of ITBS. Prospective research suggested that greater internal rotation at the knee joint and increased adduction angles of the hip may play a role in the aetiology of ITBS and that the strain rate in the iliotibial bands

of these runners may be increased compared to healthy controls. A clear biomechanical cause for

ITBS could not be devised due to the lack of CX-6258 price prospective research. (C) 2013 Elsevier Ltd. All rights reserved.”
“Multiple sclerosis (MS) is an inflammatory autoimmune disease occurring in genetically sensitive individuals. buy BTSA1 As migration of immune cells into the CNS is facilitated by the Very Late Antigen 4 (VLA-4) integrin molecule, the VLA4 gene may be considered as a plausible candidate genetic risk factor for susceptibility to MS. Therefore, the objective of our study was to investigate the association between two genetic polymorphisms located in the VLA4 gene and the risk of multiple sclerosis. One hundred seventeen MS patients and 165 control subjects from Slovakia were genotyped for VLA4 gene SNP polymorphisms at positions

269 (C/A) and 3061 (A/G). The same study cohorts were also genotyped for the rs3135388 polymorphism tagging the HLA-DRB1*15:01 allele, which is a known genetic factor associated with susceptibility to develop MS in many populations. Our findings show for the first time that the rs3135388 polymorphism is a strong risk factor for MS in the Slovak population. Investigation of the VLA4 gene polymorphisms revealed a significantly higher frequency of the 3061AG genotype in MS patients compared to the controls (P smaller Fer-1 solubility dmso than = 0.05). We suggest that the 3061AG polymorphic variant is an independent genetic risk factor for MS development in our population as it was significantly associated with this disease. The association was also confirmed after applying multivariate logistic-regression analysis adjusted for gender, age and HLA-DRB1*15:01 positivity as possible influencing factors.”
“The occurrence of primary cutaneous anaplastic large cell lymphoma (PCALCL) in immunocompromised patients is rare. Only 11 cases have been reported to date, all of them in organ transplant recipients and none in patient with idiopathic CD4+ T-cell lymphocytopaenia.

We also discuss the clinicopathologic

We also discuss the clinicopathologic Hippo pathway inhibitor features of granulocytic sarcoma in breast after bone marrow transplantation.”
“Background: In Routine Outcome Monitoring (ROM) there is a high demand for short assessments. Computerized Adaptive Testing (CAT) is a promising method for efficient assessment. In this article, the efficiency of a CAT version of the Mood and Anxiety Symptom Questionnaire, – Anhedonic Depression scale (MASQ-AD) for

use in ROM was scrutinized in a simulation study.\n\nMethods: The responses of a large sample of patients (N = 3,597) obtained through ROM were used. The psychometric evaluation showed that the items met the requirements for CAT. In the simulations, CATs with several measurement precision requirements were run on the item responses as if they had been collected adaptively.\n\nResults: CATs employing Navitoclax price only a small number of items gave results

which, both in terms of depression measurement and criterion validity, were only marginally different from the results of a full MASQ-AD assessment.\n\nConclusions: It was concluded that CAT improved the efficiency of the MASQ-AD questionnaire very much. The strengths and limitations of the application of CAT in ROM are discussed.”
“Magnetism in graphene is an emerging field that has received much theoretical attention. In particular, there have been exciting predictions for induced magnetism through proximity to a ferromagnetic insulator as well as through localized dopants and defects. Here, the authors discuss their experimental work find more using molecular beam

epitaxy to modify the surface of graphene and induce novel spin-dependent phenomena. First, they investigate the epitaxial growth of the ferromagnetic insulator EuO on graphene and discuss possible scenarios for realizing exchange splitting and exchange fields by ferromagnetic insulators. Second, they investigate the properties of magnetic moments in graphene originating from localized p(z)-orbital defects (i.e., adsorbed hydrogen atoms). The behavior of these magnetic moments is studied using nonlocal spin transport to directly probe the spin-degree of freedom of the defect-induced states. They also report the presence of enhanced electron g-factors caused by the exchange fields present in the system. Importantly, the exchange field is found to be highly gate dependent, with decreasing g-factors with increasing carrier densities. (C) 2013 American Vacuum Society.”
“Background: Patients with cancer experience multiple neuropsychiatric symptoms. Whereas individual symptoms have been studied in patients with head and neck cancer, the broader context of neuropsychiatric symptoms needs to be explored.

Finally, we found that Foxp3 bound to IL-21P and the CNS-2 enhanc

Finally, we found that Foxp3 bound to IL-21P and the CNS-2 enhancer and inhibited c-Maf-induced IL-21 production modestly but significantly in CD4(+) T cells. Taken together,

these results suggest that c-Maf induces IL-21 production directly in CD4(+) T cells JNJ-26481585 solubility dmso by activating IL-21P and the CNS-2 enhancer and that TGF-beta suppresses c-Maf-induced IL-21 production in CD4(+) T cells. J. Leukoc. Biol. 87: 703-712; 2010.”
“Chemokines and their receptors play a critical role in orchestrating the immune response during experimental autoimmune encephalomyelitis (EAE). Expression of CCR4 and its ligand CCL22 has been observed in ongoing disease. Here we describe a role for CCR4 in EAE, illustrating delayed and decreased disease incidence in CCR4(-/-) mice corresponding with diminished CNS infiltrate. Peripheral T cell responses were unaltered in CCR4(-/-) mice; rather, disease reduction was related to reduced CD11b(+)Ly6C(hi) inflammatory macrophage (iW phi) numbers and function. These results provide evidence that CCR4 regulates EAE development and further supports the involvement of CCR4 in iM phi effector function. (C) 2011 Elsevier B.V. All rights reserved.”
“Rationale: Clinical studies show that flexible dosing (maintenance and symptom-driven dose adjustments) of budesonide and formoterol (BUD/FORM) improves control of asthma exacerbations as compared to fixed

maintenance dosing protocols ISRIB solubility dmso (maintenance therapy) even when the latter utilize higher BUD/FORM doses. This Sirtuin inhibitor suggests that dose-response relationships for certain pathobiologic mechanisms in asthma shift over time. Here, we have conducted animal studies to address this issue.\n\nObjectives: (1) To test in an animal asthma-like model whether it is possible to achieve the same or greater pharmacological

control over bronchoconstriction and airway/lung inflammation, and with less total drug used, by flexible BUD/FORM dosing (upward adjustment of doses) in association with allergen challenges. (2) To determine whether the benefit requires adjustment of both drug components.\n\nMethods: Rats sensitized on days 0 and 7 were challenged intratracheally with ovalbumin on days 14 and 21. On days 13-21, rats were treated intratracheally with fixed maintenance or flexible BUD/FORM combinations. On day 22, rats were challenged with methacholine and lungs were harvested for analysis.\n\nResults: A flexible BUD/FORM dosing regimen (using 3.3 times less total drug than the fixed maintenance high dose regimen), delivered the same or greater reductions of excised lung gas volume (a measure of gas trapped in lung by bronchoconstriction) and lung weight (a measure of inflammatory oedema). When either BUD or FORM alone was increased on days of challenge, the benefit of the flexible dose upward adjustment was lost.

In cooperation with the phosphaturic hormone – Fgf23 it regulates

In cooperation with the phosphaturic hormone – Fgf23 it regulates calcium concentration by suppression of 1,25(OH),D synthesis, and reabsorption of phosphate in a distal convoluted part of nephron. Acting through these mechanisms Klotho takes part in the regulation of the mineral homeostasis of cerebrospinal fluid, blood and body fluids acting on the choroid plexus, parathyroid glands and distal Selleck FK866 Convoluted nephrons. In that way Klotho becomes one of the main players in a complex and multilevel system of maintaining the mineral homeostasis of the organism. Pol J Endocrinol 2009; 60 (2): 104-109)”
“CONTEXT Some studies have explored the role of learning

context in clerkships and in clinical teams. Very little is known, however, about the relationship between context and competence development in more loosely framed, day-to-day practices such as doctordoctor consultations, although such interactions are frequent and typical in clinical work. METHODS To address this gap in the literature, a study was conducted using semi-structured interviews in four different

hospitals and participant observation at one site. Inductive content analysis was used to Ilomastat Proteases inhibitor develop a framework. Special reference was made to the principles of situated cognition. RESULTS The framework illustrates how different situational, personal and organisational factors interact in every learning

situation. CK0238273 The interplay manifests in three different roles that doctors assume in highly dynamic ways: doctors learn as actors’ (being responsible), as participants’ (being involved) and as students’ (being taught); contextual influences also impact on the quality of learning within these roles. CONCLUSIONS The findings add to the current literature on clinical workplace learning and to the conceptualisation of context in the field of education. The practical contribution of the research lies in disentangling the complex dynamics of learning in clinical environments and in helping doctors and medical educators to increase their responsiveness to contextual factors.”
“This study presents foliar application effect of Kappaphycus alvarezii (5-15%) extract on yield and seed quality of green gram at flowering stage. Application of K. alvarezii (conc. 10.0%) significantly increased seed yield (30.11%) compared to control, due to increase in yield of pods, weight of pods as well as seed yield per plant and 100 seed weight. This treatment also improved nutritional quality of seed as follows: protein, 19.43; carbohydrate, 5.17; P, 3.61; and Mo, 52.63%.”
“Objectives: The purpose was to investigate the diagnostic performance of coronary computed tomography angiography (CTA) when non-calcified uninterpretable segments were determined as either obstructive or patent.

4% of the tumors by pyrosequencing (PS) and MSP methods, respecti

4% of the tumors by pyrosequencing (PS) and MSP methods, respectively. RASSF1A methylation evaluated by the two methods

CCI-779 supplier was more frequent in ever-smokers and tumors with TP53 mutation than in never-smokers and tumors without TP53 mutation, respectively. Univariate and multivariate analyses revealed that strong methylation was an unfavorable prognostic factor with stage I (adjusted HR, 2.25; 95% CI 1.03-4.90; P=0.003) and squamous cell carcinoma patients (adjusted HR=2.2:5, 95% CI 1.03-4.90, P=0.042). Taken together, these results suggested that quantitative PS could gain wider applications in clinical samples as a promising method for early detection screening and prognosis compared with MSP.”
“Necrotizing fasciitis is a life-threatening soft-tissue infection of bacterial origin, which involves mainly the deep fascia. Early recognition of this condition may be hampered by the uncommon nature of the disease and non-specificity of initial clinical signs and symptoms in less fulminant cases, making the role of imaging important. MRI is the most useful imaging modality in the diagnosis of necrotizing fasciitis. The presence of thick (>3 mm) hyperintense signal in the deep fascia (particularly intermuscular fascia) on fat-suppressed T-2 weighted or short tau inversion-recovery VS-6063 order images is an important marker for necrotizing fasciitis. Contrast enhancement of the thickened necrotic fascia can be variable, with a mixed-pattern of

enhancement being more commonly encountered. Involvement MK-0518 manufacturer of multiple musculofascial compartments increases the likelihood of necrotizing fasciitis. It is important to remember that T-2-hyperintense signal in the deep fascia is not specific to necrotizing fasciitis

and can also be seen in cases such as non-infective inflammatory fasciitis or muscle tear. In this pictorial essay, we aim to review the MRI findings in necrotizing fasciitis, discuss its limitations and pitfalls and identify differentiating features from non-necrotizing soft-tissue infections, such as cellulitis and infective myositis/pyomyositis, conditions which may clinically mimic necrotizing fasciitis.”
“Osteoclasts acidify bone resorption lacunae through proton translocation by plasma membrane V-ATPase (vacuolar-type ATPase) which has an alpha 3 isoform, one of the four isoforms of the trans-membrane a subunit (Toyomura et al., J. Biol. Chem., 278,22023-22030,2003). d2, a kidney- and epididymis-specific isoform of the d subunit, was also induced in osteoclast-like cells derived from the RAW264.7 line, and formed V-ATPase with a3. The amount of d2 in osteoclasts was 4-fold higher than that of d1, a ubiquitous isoform. These results indicate that V-ATPase with d2/alpha 3 is a major osteoclast proton pump. Essentially the same results were obtained with osteodasts derived from mouse spleen macrophages. Macrophages from alpha 3-knock-out mice could differentiate into multi-nuclear cells with osteoclast-specific enzymes.