If adopted, scientists and the public will have to confront the long, complex processes of human–environmental interactions that have shaped the modern world. Of these five options, we prefer the first

or the second. These recognize the deep history of widespread human impacts and send a powerful message to the scientific community and public about the role humans have played in creating our modern environmental crises. They also are broad-based with clear stratigraphic and chronological resolution in global environmental records, and established connections to human-induced changes that seem appropriate for an Anthropocene epoch. Ultimately, however the Anthropocene is defined, it is important to recognize the deep historical processes www.selleckchem.com/products/nlg919.html that underlie it. Likewise, an important practical goal should be to use the Anthropocene to educate the public and policy makers about the effects humans have had on natural systems for millennia, the compounding nature of these impacts, and the pressing need to reverse the dangerous trends and trajectories we have created. We thank

all the contributors to this volume, the many anonymous reviewers who helped strengthen the papers in it, and the editorial staff of Anthropocene – Rashika Venkataraman, Timothy Horscroft, and especially editor Anne Chin – for their help in shepherding the papers and volume through the submission, review, revision, and production process. We dedicate the volume to Paul Crutzen, who has done more than anyone to bring the Anthropocene and human domination of Earth’s

systems Protein Tyrosine Kinase inhibitor to the attention of both scholars and the general public. “
“Impacts of non-indigenous species can be ecologically devastating and are a major threat to global biodiversity (IUCN, 2013). Oceanic islands are particularly vulnerable as they often have a large proportion of endemic species with limited resilience to non-indigenous ones, and a lack of native predators to keep invasive non-indigenous species under control (Lebouvier et al., 2011). Human visitation and colonisation of remote oceanic islands and subsequent deliberate pentoxifylline or unintended introductions of invasive non-indigenous species have, in many cases, drastically modified their natural ecosystems (Connor et al., 2012). For example, the introduction of rabbits has led to catastrophic ecosystem changes through overgrazing, increased soil erosion and vegetation changes on many islands around the world (Bonnaud and Courchamp, 2011, Cronk, 1997, Hodgson, 2009 and Towns, 2011), including continental islands such as Australia, where rabbits have had devastating environmental and economic impacts (CSIRO, 2013). As a result, conservation and management efforts are increasingly focused on the control and/or eradication of invasive non-indigenous species (Bell, 2002, McClelland, 2011, Merton et al., 2002 and PWS, 2007).

Based on a previous report in which the density of the epicuticular wrinkle was incorrectly described as the

cuticle density, the densities of Yunpoong and Chunpoong were 53.0% and 17.9% respectively [20]. This finding corroborates that the density of epicuticular wrinkle is more effective against leaf NVP-BEZ235 manufacturer burning, compared to the thickness of the cuticle. Because of its characteristic morphology, epicuticular wax or the epicuticular wrinkle of epidermal surfaces can be useful as a taxonomic key of plant classification in the near future. They are also significant for researchers who have been studying the cuticle for the relationship between plants and external environmental stressors. The authors have no conflicts of interest to declare. This work was supported by a grant from Konkuk University (Seoul, Korea) in 2011. The authors gratefully acknowledge KT&G Central Institute for providing the ginseng leaves. We also thank Korea Basic Science Institute (Chuncheon, Korea) for technical assistance with scanning electron microscopy and transmission electron microscopy. “
“Ginseng (Panax ginseng Meyer) is a well characterized medicinal herb listed in the classic oriental herbal dictionary, Shin-nong-bon-cho-kyung. Afatinib manufacturer Ginseng has a sweet taste, is able to keep the body warm, and has protective effects on the five viscera (i.e., heart, lung, liver, kidney, and spleen) [1]. Ginseng can be

classified by how it is processed. Red ginseng (RG; Ginseng Radix Rubra) refers to ginseng that has been steamed

once. White ginseng (Ginseng Radix Alba) refers to dried ginseng. Black ginseng (BG; Ginseng Radix Nigra) is produced by repeatedly steaming fresh ginseng nine times. The fine roots (hairy roots or fibrous roots) of fresh ginseng that has been steamed nine times are called Fine Black ginseng (FBG). There are more than 30 different ginseng saponins with various physiological and pharmacological activities [2] and [3]. Ginsenosides are divided into two groups: protopanaxadiols and protopanaxatriols. The root of Panax ginseng reportedly has various biological effects, including anticarcinogenic effects. One study showed that ginseng extracts induce apoptosis and decrease Cyclin-dependent kinase 3 telomerase activity and cyclooxygenase-2 (COX-2) expression in human leukemia cells [4]. In addition, ginseng extracts suppress 1,2-dimethylhydrazine-induced colon carcinogenesis by inhibiting cell proliferation [5]. Until recently, research on anticancer effects of ginseng has focused on ginsenoside Rg3 (Rg3) and ginsenoside Rh2 (Rh2). Ginsenoside Rg3 is not present in raw ginseng or White ginseng, but is synthesized during heating hydrolysis; thus, only a small amount of Rg3 is present in Red ginseng. Ginsenoside Rg3 has an anticancer effect by suppressing phorbol ester-induced COX-2 expression and decreasing activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) [6].

Two patients in the 60-U/kg treatment group Entinostat cost experienced 8 events that were considered to be treatment-related by the investigator; the first patient reported 3 occurrences of itchy throat and 1 occurrence of chest discomfort, and the second patient reported 1 occurrence of gastroenteritis and 3 occurrences of vomiting. Both patients were pre-medicated with H1 blockers and are continuing in the extension study. No patient withdrew from this trial due to an AE. No clinically significant laboratory test abnormalities (hematology,

serum and urinary chemistry) were noted. There were no clinically significant mean changes from baseline observed at the end of the study in any of the laboratory safety parameters. The majority of the vital sign measurements were within normal limits, none of the changes or the measurements outside of the normal limits were clinically significant. Abnormal echocardiography results at month 12 were reported for 2 patients: One patient receiving the 60-U/kg dose had mild tricuspid regurgitation and 1 patient in the 30-U/kg group diagnosed with Type 3c GD (subtype known to have a cardiac involvement) [1], [17] and [18] had a baseline echocardiography that revealed abnormal atrioventricular and mitral valves with

an insufficiency gradient of 30 mm Hg. At study end, the echocardiography results showed pulmonary hypertension with an abnormal tricuspid insufficiency gradient of 74 mm Hg, which was considered a clinically significant deterioration Dabrafenib in vivo but was deemed not related to study treatment. Two patients were found to be IgG positive for anti-taliglucerase-alfa antibodies in at least 1 post-treatment visit; however, this finding did not affect the continued improvement of GD parameters throughout the course of the study. An additional patient was found to be IgG positive at the pretreatment sample and became negative as the trial progressed; this patient also improved clinically as noted above for the other 2 patients. All positive titers were low (< 550). Assay results for neutralizing antibodies (in vitro enzymatic inhibition assay and cell-based neutralizing

assay) were negative for all 3 patients. No apparent association was noted between anti-taliglucerase antibody and safety or efficacy. This study is distinguished among studies of ERT Progesterone for GD in that it is focused exclusively on treatment-naïve pediatric patients. This pediatric study followed the design of the pivotal study in adults regarding dosage, wherein patients were randomized to receive taliglucerase alfa either 30 or 60 U/kg, every other week. However, in this study, the duration was 12 months instead of 9 months and the primary end point was improvement in hemoglobin rather than reduction in spleen volume. At the end of this study, clinically significant improvements were observed in hemoglobin concentration, platelet counts, spleen volume, and liver volume, as well as in GD biomarkers.

In two cases the VAV curves did not have a well-defined maximum which is shown for H. stephensii venom with TSAV and A. antarcticus venom with DAAV, which

had broad VAV peaks with two maxima ( Fig. 2D and E). T. carinatus with TSAV and P. porphyriacus with both BlSAV and TSAV had distinct maxima in the VAV curve (data not shown). E. carinatus and E. ocellatus venoms (250 ng/ml) were incubated with Indian polyvalent antivenom and applied to a plate coated with anti-E. ocellatus antibodies and D. russelii venom (250 ng/ml) was incubated with Indian polyvalent antivenom and applied to a plate coated with anti-D. russelii antibodies. Detection was with labelled anti-horse antibodies. Fig. 4 shows a clear VAV peak for D. russelii venom buy Ipilimumab but not for E. carinatus venom. The antivenom concentration where there was a peak in absorbance due to VAV increased with increasing venom concentration and was determined using the fitted curves. Fig. 5 shows the linear relationship between the antivenom concentrations for the VAV peak versus venom concentration over the venom range of 50 ng/ml to

500 ng/ml. The slope of the lines can then be interpreted as the ratio of antivenom to venom where there is HSP inhibitor a peak in absorbance from venom–antivenom complexes. This varied between 0.04 and 0.15 mU/ng for all Australian commercial venoms (Table 1, Fig. 5A) and was 0.09 U/μg (95%CI: 0.07–0.12 U/μg) for P. textilis venom, 0.04 U/μg (95%CI: 0.035–0.05 U/μg) for N. scutatus venom and 0.08 U/μg (95%CI: 0.06–0.10 U/μg) for O. scutellatus venom. For D. russelii venom the slope of the line was 180 ng AV/ng ( Fig. 5B). To examine the behaviour of individual venom components, we collected four well-defined fractions from the HPLC of N. scutatus venom ( Fig. 6). Each fraction comprised 6–8% of the total

area of the HPLC trace. The fractions were characterised (-)-p-Bromotetramisole Oxalate by mass spectrometry and matched to previous structures as: Fraction I – notexin (13,544 Da), fraction II (16,742 Da), fraction III (14,002 Da) and fraction IV – notecarin (46,678 Da). Fraction II could not be matched to a previously isolated structure. Fraction III matched to a phospholipase A2 toxin in Acanthophis sp. (acanmyotoxin-3 [fragment]). The prothrombin activator Notecarin has previously been isolated in this manner, and shown to consist of two peaks corresponding to two isoforms ( Rao et al., 2003). Fraction II and Notecarin bound poorly to the rabbit anti-N. scutatus antibodies used to coat the plate so VAV measurement with these fractions was not possible. Notexin and fraction III produced VAV curves similar to whole venom, but with maxima displaced to higher or lower TSAV concentrations compared to whole venom ( Fig. 7). RVVFX, the FX-activating component from RVV, was mixed with Indian polyvalent antivenom and assayed for VAV. A set of VAV curves was obtained at RVVFX = 50, 100, 250 and 500 ng/ml, showing a concentration of AV at VAVmax as 8, 18, 36 and 66 μg/ml (Fig. 3).

Similarly, the translocation frequency of the Igh and Myc loci which are located on different chromosomes in mouse B lymphocytes directly correlates to their contact frequency in a 4C-seq experiment [ 34]. Furthermore, the actual observed intra-and inter-chromosomal translocation frequency has been shown to correlate with the contact probability in a Hi-C experiment in G1 arrested mouse MAPK inhibitor pro-B cells [ 35••]. Within the fractal globule, chromatin is organized into discrete domains. A Hi-C analysis in mouse ES cells identified

2200 topological domains in which chromatin with a median size of 880 kb occupying about 91% of the genome interacts locally [36••]. These topological domains are enriched in housekeeping genes and SINE elements, and are separated by topological boundary regions with characteristics of insulator elements, such as CTCF-binding and a segregation of the heterochromatic H3K9me3 mark [36••]. This

organization of the topological domains is conserved between different human cell types, as well as between human and mouse [36••]. A follow up study by the same group using the ChIP-seq technique found a significant overlap of topological domains with cis-regulatory enhancer-promoter units in 19 embryonic and adult mouse tissues and cell types [37]. Similarly, a 4.5 Mb region encompassing Xist on the X chromosome in mouse ES cells was shown to partition into discrete topologically JQ1 associating domains (TADs)

that are 200 kb to 1 Mb in size, and are present on both the active and inactive X chromosome in male and female ES cells [38••]. While they are enriched in, they do not require H3K27me3, H3K9me2 nor lamina-associated domains (LADs) for their maintenance [38••]. Within a TAD, genes are transcriptionally co-regulated, and while the TADs as a whole do not change, the internal TAD contacts rearrange upon ES cell differentiation supporting the link between chromatin structure and transcription [38••]. Similarly, a study of the active and inactive X-chromosome in human SATO3 lymphoblast cells revealed that transcription disrupts intrachromosomal interactions, leading to local chromatin decompaction Tau-protein kinase at promoters [39]. A 5C study as part of the ENCODE project analyzed the interactions of transcriptional start sites (TSS) in 44 regions representing 1% of the genome in three human cell lines [40]. More than 1000 mostly asymmetric long-range interactions with distal elements resembling promoters and enhancers were identified within these regions [40]. However, in contrast to another study [37], ∼60% of the interactions were found in only one of the three cell lines analyzed indicating a cell-type specific chromatin folding [40]. Therefore, it remains to be determined how conserved these long-range interactions are between cell types or species.

Histopathologically, the tumors of MS- and sham-exposed mice are not different. Also, their distribution within the lungs is not different. In the current and in previous A/J mouse studies discussed above, lung tumors in smoke-exposed mice were on average smaller and there was a trend to a lower degree of malignancy compared to those in sham-exposed mice. Both effects may, however, be due to a delayed tumorigenic process by concomitant smoke exposure compared to spontaneous tumorigenesis, as previously discussed ( Stinn et al., 2010 and Stinn et al., 2012). In the current study, a Nutlin 3a clear difference between tumor tissues from MS- and

sham-exposed mice was evident based on a gene expression signature, which clearly discriminated MS-exposed tissues from sham-exposed tissues with an overall predictive success rate of 95%. The tissues used for the gene expression analysis were harvested after a 2-day post-inhalation period in order to allow Dabrafenib order recovery of acute smoking-related gene expression effects, such as those regulated by the aryl hydrocarbon receptor (AhR). A rapid recovery of acute smoke exposure effects on gene regulation has been observed in previous

studies (Gebel et al., 2010 and Haussmann et al., 2009), and indeed the induction of cyp1a1 as the most prominent representative of these acute AhR-dependent effects decreased from approximately 300-fold to approximately 2-fold in non-tumor tissue in the 2-day post-inhalation period in the current study (more details oxyclozanide to be published elsewhere). Nevertheless, the qualitative difference of the tumors of MS- and sham-exposed mice may be related to

a sustained change in gene expression due to MS inhalation lasting longer than the 2-day recovery period. This interpretation is favored by the 95% accuracy in allocation of tumors to MS exposure on the basis of the gene expression signature. This is more accurate than one could expect based on a roughly 4-fold increase in MS-induced tumor multiplicity beyond control, which theoretically could be based on 1/4 of tumors having developed spontaneously and 3/4 having specifically been induced by the smoke exposure. Inflammatory effects may be involved in the tumorigenesis of MS in this model. Such effects were investigated and discussed in detail in Study 1 (Stinn et al., 2012), but were not assessed in the current study. In order to provide an indication of the reproducibility of inflammatory effects, the major inflammatory endpoint in this type of study, i.e., the accumulation of neutrophils in the lungs analyzed upon bronchoalveolar lavage, can be compared among studies. The percentage of neutrophils in Study 1 at the end of the 5-month inhalation period at an MS concentration of 298 mg TPM/m3 was 33% relative to all cells harvested.

Therefore, the ratios of the observed to the predicted SSC along the depth were calculated at each

cross-section. Figure 5 and Figure 6 show results for cross-sections T1 and T2 respectively. At each cross-section two monitoring points, one in shallow part and the other in deeper part were considered. In each figure, the plots in the left show the ratios during a whole ebb phase and the ones in the right show the ratios for duration of a flood phase. The monitoring point in a shallow part of the cross-section and its corresponding results are shown in blue and those for the deep part are presented in red. It is obvious on the figures that observed SSCs in shallow parts are appreciably higher than predicted ones. It can also be seen Selleck Torin 1 that the ratio of observed to predicted SSCs are much larger during the ebb phase than that during flood phase especially in near bed layers. It can be seen from the results that the deviation between the model results and field data do not show similar trend along the depth. Taking into account that the model has been calibrated against SSC, observing such deviation can be attributed mostly to the field data. Therefore dissimilarities

observed specifically in selleck inhibitor the shallow regions are expected to be related to the existence of some error in measuring devices. Existence of biological matter and generation of air bubbles in such regions can be counted as the reason for the error in measuring device. Suspended sediment concentrations measured in the field using transmissometer were compared with those derived from Delft3D model. Dissimilarities between the modelled and

measured SSC were mainly observed in the shallow regions of cross-sections T1 and T2. This was supposed to be partly due to in situ measurements’ shortcomings and partly was attributed to the imperfections of the theoretical modelling approaches incorporated in the Delft3D software. Wide range of particle size distribution in shallow water areas could be counted as a possible reason for the dissimilarity observed. Gordon and Clark (1980), Bishop (1986), Moody et al. (1987) and Bunt et al. (1999) reported Non-specific serine/threonine protein kinase that the variation in particle size distribution is the most influential physical characteristic of the sediments on the response of optical devices. Bunt et al. (1999) suggested that variations in floc size could double the variation in instrument response for similar mass concentrations. Existence of biological matter in shallow water area can also affect the recorded data by transmissometer. As pointed out by Walker (1981), biological matters such as chlorophyll-a and phytoplankton even though relatively insignificant by mass, their effect on the response of optical instruments is significant. These organisms are known to be active in the shallow areas where light is sufficient. The sticky nature of these particles causes flocculation between the fine particles.

Eggs extracted from gravid females were examined under a microscope at x1, x2, x4 and x6.3

using reflected light. Digital photographs of eggs were taken with a DS-Fi1 5.0-megapixel digital camera (Nikon, Japan). Embryonic development was defined according to the embryo development scale for DAPT cell line the Chinese mitten crab given by Peters (1938) and for the blue king crab Paralithodes platypus given by Stevens (2006). Results were expressed as a mean with standard deviation (mean ± SD). The relationship between female carapace width and eggs wet weight was determined by linear regression analysis (y = ax + b) with a coefficient of determination R2 for a significance level P < 0.05. The carapace width of females (N = 22) collected in the Gulf of Gdańsk and Vistula Lagoon varied from 55.20 to 78.10 mm (mean 62.46 ± 5.09 mm). Detailed information on size, weight and gonad maturity stage of all the Chinese mitten crab females are given in Table 1. Most of the females (N = 17) were in the G4 gonad developmental stage; only four females had eggs on pleopods, thereby belonging to the G5 gonad developmental stage. The gonad maturity stage was not correlated with

female carapace width. The wet weight of eggs ranged from 12.16 to 31.00 g (mean 21.84 ± 8.75 g), which accounted for 17.9 ± 2.9% of the egg-carrying female weight on average. Eggs wet weight (EW) was significantly correlated (P < 0.05, R2 = 0.58) with female carapace width (CW) according to the equation EW = 2.16CW – 110.78. On the basis of photographs ( Figure 1) it was found that extracted embryos were between the selleck initial phases of the 3rd and 4th developmental stages, and characterised by a lack of visible cells and structures. The embryonic lobes would probably become visible Astemizole in the following days. Based on the gonad maturity stage it is assumed that the females were shortly before (stage G4) or after (stage G5) copulation and the eggs were in the 3rd and 4th embryo development stage. According to Stevens (2006) the 3rd embryo stage in the blue king crab lasts about 114–156 days

after copulation, whereas the 4th stage lasts about 157–170 days. Thus, based on the sampling time (November/December) as well as on the embryo development stages one can assume that the examined egg-carrying females had copulated at least 3 months previously. The eggs were tightly attached to the female pleopods and extracting them for analysis was time-consuming. This is rather surprising, because the gravid females were collected at a salinity of 7 PSU. According to Peters (1938) and Panning (1939) the ‘cement-like’ substance that attaches the eggs to the egg-carrying setae does not harden at salinities lower than 14 PSU and females lose their eggs. Although Peters (1938) conducted some successful laboratory experiments with egg-carrying females at 6.5 PSU, to date no evidence of such a situation in a natural environment has been forthcoming.

Na altura terá feito estudo para doença celíaca que foi negativa. Por análise retrospetiva dos exames de imagem realizados atualmente, pode constatar-se que a suposta invaginação descrita na TC abdominal nada mais era do que a presença do DDI, verificando-se a imagem característica do sinal em «halo». O trânsito duodenal foi de grande importância no diagnóstico do DDI, mostrando o tão característico sinal de «windsock». No estudo com EDA observou-se um esófago com aspeto traqueiforme, duodeno

com pregas espessadas condicionando estenose relativa com restos alimentares impactados e mucosa erosionada e friável. Embora ABT199 essas alterações macroscópicas sejam incaracterísticas, tem-se constatado a sua presença em doentes com GEE mucosa. Foi a histologia que ditou o diagnóstico de GEE mucosa. Ao contrário de alguns casos publicados, neste doente não se visualizou o orifício de entrada do DDI via EDA10. Dorsomorphin No caso clínico exposto, a sintomatologia apresentada era escassa e não é a típica de

GEE ou DDI. Provavelmente, a febre inexplicada, com cedência aos antibióticos, poderia estar associada a síndrome de hiperproliferação bacteriana, tanto pela presença do DDI como pelas erosões da mucosa que permitiriam que agentes microbianos atravessassem a barreira intestinal. O tratamento da GEE baseia-se fundamentalmente na corticoterapia (prednisolona 20-40 mg/dia) durante 8 semanas4, com redução progressiva, e visa a resolução dos sintomas14. Em casos graves, corticodependentes ou corticorresistentes, os imunossupressores (azatioprina ou 6-mercaptopurina) constituem uma alternativa1 and 4. Atendendo a que o doente se encontrava sintomático, mas sem gravidade, e que a maioria dos casos de GEE responde aos corticosteróides com uma

taxa de sucesso de 90%, optou-se por instituir corticoterapia. No nosso doente, a resposta terapêutica foi imediata. Contudo, em virtude do caráter crónico da doença, com remissões e recaídas frequentes, apesar do seu caráter benigno, estes doentes devem ser mantidos em consultas de seguimento. Embora, o tratamento tradicional dos pacientes com DDI sintomáticos e de grandes dimensões seja a resseção cirúrgica, atualmente preconiza-se incisão endoscópica13. No caso clínico apresentado, tendo em conta as dimensões do Phosphatidylinositol diacylglycerol-lyase DDI (quase 4 cm) e o caráter progressivo desta entidade, colocou-se a hipótese de resseção do DDI. Assim, poder-se-iam evitar possíveis complicações futuras. Apesar da unanimidade em considerar a etiologia da GEE desconhecida, pensamos que o raciocínio fisiopatológico apresentado para explicar a relação causal entre o DDI e a GEE é plausível e, de todo, não desprezável. A grande limitação neste caso é demonstrar a veracidade deste raciocínio fisiopatológico, porque poderemos apenas estar perante um caso clínico com 2 diagnósticos independentes e raros.

Conditioned medium from macrophages, osteoclasts and treated osteoclasts all Inhibitor Library price significantly increased CD69 expression on γδ T cells to a similar extent (Fig. 3). This was in contrast to our findings with CD4+ T cells, since conditioned medium from macrophages or untreated osteoclasts consistently failed to induce upregulation of CD69 on CD4+ T cells. However, conditioned medium from treated osteoclasts did induce a significant increase in CD69 expression on CD4+ T cells. Taken

together, these results indicate that γδ T cell activation by macrophages or osteoclasts is mediated by soluble factors and does not fundamentally require cell–cell contact. However, the stimulatory effect of osteoclasts on CD4+ T cells requires co-culture conditions, suggesting that cell–cell interactions play an important role in this process. TNFα is a potent stimulator of T cell activation and is capable of co-stimulatory effects on T cell survival [23] and [24]. We therefore investigated whether macrophages and osteoclasts were triggering γδ T cell activation CT99021 research buy via production of TNFα. Using a neutralising anti-TNFα antibody we observed that the stimulatory effect of macrophage- and osteoclast-derived

conditioned medium on CD69 expression by γδ T cells was significantly reduced versus the isotype control (Fig. 4). There was also a trend for TNFα neutralisation to diminish the stimulatory effects of treated

osteoclast-derived conditioned medium but this was not statistically significant versus the isotype control. While the stimulatory effect of conditioned medium on γδ T cell activation was attenuated by anti-TNFα treatment, tuclazepam it was not abolished entirely, indicating that other stimulatory factors are present in osteoclast-derived conditioned medium that trigger γδ T cell activation. Following our observation that osteoclasts induce γδ T cell activation we then sought to determine whether these stimulatory effects of osteoclasts could trigger proliferative responses in γδ T cells. Using CFSE-labelled γδ and CD4+ T cells in co-cultures with autologous osteoclasts, we observed no proliferative effects of autologous osteoclasts on unstimulated γδ T cells or CD4+ T cells (Fig. 5A). However, activation of γδ T cells with IL-2 (which induced marked upregulation of CD69 on γδ T cells — Fig. 3A) resulted in extensive proliferation of γδ T cells, and this proliferative effect was further enhanced by co-culture with osteoclasts (Fig. 5A). In contrast to this, CD4+ T cells did not exhibit any proliferative responses to IL-2 alone or in co-culture with osteoclasts. This suggests that unstimulated osteoclasts provide co-stimulatory signals that augment IL-2-induced γδ T cell proliferation, but such co-stimulatory signals do not confer responsiveness of CD4+ T cells to IL-2 stimulation.