Ultimately, differences

in performance across phonetic contrasts may derive less from their phonological status (e.g., consonant versus vowel) and more from the statistical structure of the cues to these contrasts, particularly when we look across multiple relevant AZD1208 and irrelevant dimensions. For example, cues like VOT do vary between speakers (Allen, Miller, & de Steno, 2003), but they are largely discriminable without taking this into account; therefore, high variance in speaker cues will quickly reveal the more invariant contrastive VOT cues. However, for vowels, and to a lesser extent, fricatives and liquids, contrastive and noncontrastive acoustic dimensions overlap substantially (vowels: Hillenbrand, Daporinad chemical structure Getty, Clark, & Wheeler, 1995; fricatives: Jongman, Wayland, & Wong, 2000). These contrastive dimensions, such as formant structure, F0, and length, are also cues that vary considerably by speaker. In order to use speaker variation to detect such differences, infants may need more sophisticated ways of dealing with this variability or may simply need to learn more about those things that contribute to variance (Cole, Linebaugh, Munson, & McMurray, 2010) before vowel can be a cue to word identity. As a result, failures

in the switch task at 14 months do not represent a reversal of development, a U-shaped curve, or a discontinuity. We suggest rather that speech perception was never fully developed at 12 months, as is evidenced by studies of older children (Nittrouer, 2002; Ohde & Haley, 1997; Slawinski & Fitzgerald, 1998). Reliance largely on discrimination measures resulted in a failure to consider other factors (like dimensional weighting)

that are revealed by this task. This study hints that dimensional weighting is sensitive to the relative variation along different dimensions. This may in fact represent a general principle of learning. For example, the role of irrelevant variation suggested by this work parallels mechanisms proposed by Gómez (2002) for statistically determined grammatical dependency structures. Adults and infants learned a novel grammar with nonadjacent dependency structure. When intervening elements in the dependency were long and variable, both adults and infants detected the nonadjacent dependencies. When Loperamide intervening elements did not vary, participants were unable to learn the grammatical dependencies. Consequently, learning of grammatical dependencies in Gómez’s experiment requires high variability in those elements that are not criterial for determining the grammar. Yu and Smith’s (2007) work on learning word–object mappings via cross-situational statistics illustrates the same point. In this study, subjects learned a small set of word–object mappings solely by noticing the statistical relationship between the sound and the object: whenever a given word was heard, the referent was consistently present.

Structurally, the purpose of the placenta in mammals is to bring maternal and fetal circulatory systems in close proximity to facilitate exchange of nutrients, oxygen, waste, and other factors.[2] Several good reviews of comparative placentation exist.[3-7] Placentae are usually described by the layers existing between fetal trophoblast, which itself envelops fetal vessels and mesenchymal

cells, and maternal blood.[2] The controversy of placentation and the validity of animal models will likely continue because while it is assumed that differences in placentation will lead to different adaptive mechanisms, experimental changing of placentation in certain animals is likely extremely challenging. The human placenta is said to be hemochorial,[2] in that maternal blood is in direct contact with DNA Damage inhibitor fetal trophoblast. There are, however, other points of contact between U0126 order maternal and fetal tissues, for example in the villous structures that anchor the placenta.[8] The human placenta moreover is said to be interstitial, in that implantation occurs completely within the maternal uterine wall[4] thus allowing for multiple points of interaction between maternal and fetal tissues early in gestation. Primates commonly used in research, for example baboons, macaque, chimpanzee, also have hemochorial placentas[3,

6] with more or less invasion upon implantation, and a villous organization, although this is not true for all primates (e.g. lemurs[3]). The vascular structure of human placenta undergoes a revision in early gestation in which trophoblast lines maternal uterine arteries[9] to allow for maximal blood flow.[10] The placenta in rats (see recent review by Soares et al.[11]) mice, and guinea pigs (rodents) is similar to that in humans

in that maternal blood is in direct contact with trophoblast. There are subtle(?) structural differences between human and rodent placentae, including the flow of blood due to a labyrinthine as opposed to a villous organization, the depth of trophoblast invasion,[6] and the trophoblast subpopulations.[2] For example, an additional layer of trophoblast, the giant cell layer, in addition to cytotrophoblast and syncytital Phosphoprotein phosphatase trophoblast has led some authors to call the rodent placenta ‘hemotrichorial’. Because of only one trophoblast layer, the guinea pig placenta is sometimes referred to as ‘hemomonochorial’. In addition to structural differences, there are subtle differences in the expression of proteins, such as those involved in immune regulation.[12-15] While the definitive placenta is in place for a short time relative to gestation in mice and rats,[2] the longer gestation in guinea pigs makes this less true. Rabbits belong to the group of mammals called lagomorphs. Their placentas are hemochorial with two trophoblast layers, a syncytium layer and a cytotrophoblast layer, which is similar to humans, but organized in a labyrinthine structure.

After treatment with the Tanespimycin probiotic, inflammatory biomarker levels significantly decreased. Uraemic rats demonstrated superficial mucosal

erosion and inflammatory cell infiltration in the small intestine, and administration of the probiotic alleviated these lesions. The probiotic B. animalis subsp. lactis Bi-07 alleviate bacterial translocation and ameliorate microinflammation through the recovery of intestinal mucosal integrity. “
“Background:  Accurate estimation of glomerular filtration rate (GFR) allows early detection of renal disease and maximizes opportunity for intervention. Aim:  To assess the accuracy of estimated GFR (eGFR) in an Australian and New Zealand cohort with chronic kidney disease using the 4-variable Modification of Diet in Renal Disease equation (MDRD4V), the Chronic Kidney Disease check details Epidemiology Collaboration (CKD-EPI) equations, and the Cockcroft and Gault equation

with actual and ideal body weight. Methods:  Retrospective review of patients who had measured GFR (mGFR) by 51Cr-EDTA clearance and simultaneous measurements of serum biochemistry and anthropometrics. eGFR was compared with mGFR using the concordance correlation coefficient (CCC) and Bland–Altman measures of agreement. Results:  178 patients had 441 radioisotope measurements of GFR. Mean mGFR of was 22.6 mL/min per 1.73 m2. The MDRD4V equation using the ‘black’ correction factor was most accurate with a mean eGFR of 19.74 (CCC 0.733, bias −2.86). The CKD-EPI equations also using the ‘black’ correction factors were almost as good at 19.11 (CCC 0.719, bias −3.49). The Cockcroft–Gault creatinine clearance values had the poorest agreement with mGFR. In the 18 nonwhite non-Asian patients, the MDRD4V and CKD-EPI equations were generally less accurate although the

use of the ‘black’ correction factor resulted in greater accuracy for both Gemcitabine price equations. Conclusion:  The MDRD4V equation was the most accurate. However, its accuracy might be less for nonwhite non-Asian patients if the ‘black’ correction factor is omitted. Further study of the estimation of GFR in Australian and New Zealand ethnic subgroups would be helpful. “
“Early intervention in patients with chronic kidney disease (CKD) significantly improves the prognosis. The present widely used markers of renal function, such as serum creatinine (sCr), fail to reflect early renal damage and predict the progression of disease. The authors aimed to evaluate whether neutrophil gelatinase-associated lipocalin (NGAL), a novel specific biomarker of acute kidney injury, could predict the progression of CKD. We identified 92 patients with stage 2–4 CKD caused by primary chronic glomerulonephritis. The patients were followed for 2 years, the changes in NGAL levels in the progressive and non-progressive groups were compared. First, the serum NGAL levels of patients with stage 2–4 CKD were significantly increased compared with the control group.

gattii molecular type VGII. The isolation of C. gattii VGII in the downtown city of

Cuiabá is important because it fits in the Northern Macroregion, suggesting expanding and urbanisation of this genotype in different Brazilian cities. “
“Summary  There is a biological plausibility on the link between cystic fibrosis transmembrane conductance regulator (CFTR) mutations and allergic bronchopulmonary aspergillosis (ABPA). The aim of the systematic review was to investigate this link by determining the frequency of CFTR Temozolomide order mutations in ABPA. We searched the PubMed and EmBase databases for studies reporting CFTR mutations in ABPA. We pooled the odds ratio (OR) and 95% confidence intervals (CI) from individual studies using both fixed and random effects model. Statistical heterogeneity was evaluated using the I2 test and the Cochran-Q statistic. Publication bias was assessed using both graphical and statistical methods. Our search yielded four studies (79 ABPA, 268 controls). The odds of encountering CFTR mutation was higher in ABPA compared with the control group (OR 10.39; 95% CI,

4.35–24.79) or the asthma population (OR 5.53; 95% CI 1.62–18.82). There was no evidence of statistical heterogeneity or publication bias. There is Selleckchem Erlotinib a possible pathogenetic link between CFTR mutations and ABPA. However, because of the small numbers of patients, further studies are required to confirm this finding. Future studies should adopt a uniform methodology and should screen for the entire genetic sequence of the CFTR gene. “
“Febrile neutropenic patients are at greater risk

of getting bacterial and fungal infections. Empirical antifungal therapy is considered if the fever persists despite broad-spectrum antibiotics including vancomycin. However, the timing of initiating empirical antifungal therapy can vary from 3 to 8 days of non-response to antibiotics. We choose to determine the response of empirical amphotericin B deoxycholate (dAMB) starting either on day 4 or day 8 in febrile Chorioepithelioma neutropenic patients not responding to broad-spectrum antibiotics and without localisation of fever. Fifty-six patients with persistent neutropenic fever despite 72 h of antibiotic therapy were randomly assigned to receive dAMB either starting on day 4 (group A, n = 27, median age 23 years) or starting on day 8 (group B, n = 29, median age 25 years). Satisfactory response (patient remaining afebrile for 48 h and maintaining absolute neutrophil count >500 μl−1) occurred in 85.2% of patients in group A vs. 69.5% in group B (P = 0.209). Patients in group A took significantly fewer days to become afebrile than group B (5.4 ± 3.9 days vs. 11.3 ± 4.0 days, P = 0.0001). The adverse side effects of dAMB (nephrotoxicity, hypokalemia and hypomagnesemia) occurred at similar rates in both groups. Early addition of empirical dAMB in febrile neutropenic patients leads to their early defervescence and decreased dose requirement.

1 before and during infection resulted in decreased morbidity and mortality compared to control influenza-infected mice. Not only did a portion of treated animals survive, those surviving animals also experienced rapid recovery to a normal weight range. These findings implicate NK cells in contributing to or exacerbating pathology arising from influenza infection. This contrasts with the described essential function of NK cells in protecting mice from influenza infection, selleck screening library as evidenced by increased morbidity and mortality when NK cells are depleted or rendered less responsive [24-26]. Previous studies have generally used low doses of influenza virus to study NK cell functions and in this case NK

cells may contribute significantly to limiting the early propagation of virus. In comparing our experiments with those in previous reports, it appears that virus dose plays a role in determining the overall influence of NK cells in host morbidity and mortality as a consequence of influenza infection. Here, we clarify this issue by showing that increasing the influenza dose from medium to high switches the contribution of NK cells from reducing to enhancing morbidity and mortality. Our results with high-dose influenza infection confirm recent findings by Abdul-Careem et al. [36], where they observe NK cells contributing to pathology during influenza infection. Unlike our study, Abdul-Careem et

al. did neither examine virus dose vis-à-vis the NK-cell contribution to pathology during selleckchem influenza infection, nor define the importance of this factor, however, the single dose of virus they used may be similar to the high-dose virus level we used in this study, since they obtained similar outcomes [36]. Interestingly, for LCMV PTK6 infection in mice, it has been demonstrated that the dose of virus greatly affects the influence of NK cells in the immune response to the virus and host outcome. A low dose of LCMV results in viral clearance; a medium dose results in a deleterious

NK-cell dependent alteration of T-cell responses, immunopathology, and virus persistence; while with a high dose of virus, NK cells are beneficial by suppressing T cells that would otherwise mediate severe pathology and mortality [13]. It is conceivable that at high influenza dose, the outcome we observed is similar to that seen with infection of mice with a medium dose of LCMV, where there is NK-cell dependent pathology. The age of mice is another factor affecting host pathology and mortality in the context of influenza infection. This can be seen in comparing the survival curves of the unmanipulated influenza infected control groups in Figures 3 and 5. None of the influenza infected control mice in Figure 3 survived, while approximately 30% of the mice used in Figure 5 did survive the same dose of influenza infection. The mice used in Figures 3 were 4 months old, while those used in Figure 5 were 2 months old.

There were no false positives or negatives in either group. One flap loss in the clinically monitored group resulted in limb amputation (the only amputation in the cohort). Conclusion: A trend toward early detection and salvage of flaps with anastomotic insufficiency was seen with the use of the Cook–Swartz implantable

Doppler probe. These findings suggest a GSK-3 activation possible benefit of this technique as a stand-alone or adjunctive tool in the clinical monitoring of free flaps, with further investigation warranted into the broader application of these devices. © 2009 Wiley-Liss, Inc. Microsurgery 30:354–360, 2010. “
“In this report, we present a case in which a free anterolateral thigh (ALT) flap was transferred for head and neck reconstruction after oropharyngeal cancer ablation, and a retrograde arterial inflow was used to salvage the flap when the main arterial pedicle showed usual repeated spasms. The flap was raised as a chimera flap comprising a fasciocutaneous flap and a vastus lateralis muscle flap. After reperfusion, the pedicle artery exhibited spasms repeatedly and vascular flow was unstable. Therefore, we performed arterial supercharge. In the distal portion of the muscle flap, a small arterial branch was dissected as a reverse-flow arterial pedicle. The recipient artery was buy Ixazomib also a retrograde limb of the superior thyroid artery. The flap survived; however, postoperative ultrasonographic echo evaluation revealed that the spastic descending

branch of the lateral circumflex femoral artery was obstructed and that the reverse-flow muscular perforator alone nourished the whole flap. In free ALT flap transfer, a small perforator level artery was able to nourish a flap, even in a retrograde manner. Moreover, when the vasculature of the free flap is unstable, retrograde arterial supply to a small perforator can be an option to save the flap transfer. © 2012 Wiley Periodicals, Etofibrate Inc. Microsurgery, 2012. “
“In the treatment of head and neck carcinoma,

radical cervical lymphadenectomy leaves the affected side of the neck devoid of the sternocleidomastoid muscle, thus more vulnerable to the unwanted side effects of the adjuvant radiotherapy. It also causes asymmetry and cosmetically unpleasant appearance of the cervical region. In the reported case with widely ulcerated squamous-cell carcinoma over mandible, hemimandibulectomy and radical neck dissection was performed. Following the mandibular reconstruction, the lateral hemisoleus muscle of the harvested osteomyocutaneous fibula flap was utilized to restore the ipsilateral sternocleidomastoid region. This new application promises to be a useful method, which can aid in the restoration of the aesthetic contour of the neck and provide protection against unwanted effects of the adjuvant radiotherapy on the ipsilateral carotid artery. © 2011 Wiley-Liss, Inc. Microsurgery 2011. “
“Soft palate reconstruction is one of the greatest challenges for reconstructive surgeons.

Our results thus provide a novel mechanistic basis reconciling previous opposite observations in the field of infections and T1D. In addition, our finding that stimulation through

TLR2 constitutes a well-suited means to expand CD4+CD25+ Tregs while ameliorating their tolerogenic function in T1D opens new possibilities for therapy of this disease and possibly other autoimmune disorders. NOD/ShiLtJ mice, and WT or TLR2−/− C57BL/6J (B6) mice were purchased from the Jackson Laboratory. C57BL/6-RIP-GP (B6 RIP-GP) transgenic mice were described previously 5, 6. For infection, a single dose of 104 PFU LCMV Armstrong 53b was given BI 2536 chemical structure intraperitoneally. Blood glucose was monitored using OneTouch Ultra system (LifeScan), and mice exhibiting values greater than 300 mg/dL were considered diabetic. Animal work in all studies was approved by the LIAI Animal Care Committee. All injections were performed intraperitoneally in 200 μL volume. Tregs, DCs, and mouse anti-mouse TLR2 mAb (Invivogen) were injected in PBS, and P3C (EMC Microcollections) was injected in DMEM (Invitrogen). Pancreas was collected and snap-frozen at the indicated time point after treatment. Frozen sections were stained with hematoxylin and eosin, and insulitis was scored blinded, as follows: (0) no insulitis, (1) peri-insulitis with no islet destruction, (2) severe peri-insulitis and some infiltrating insulitis, (3)

infiltrating insulitis Selleck C646 and some islet destruction, (4) infiltrating insulits and extensive islet destruction (or islet destroyed). Cells were stained with fluorescently labeled mAbs (BD Biosciences, eBioscience, BioLegend, Caltag) as described previously 12. Suplatast tosilate Samples were processed on a LSRII or FACScalibur (BD Biosciences) and results analyzed using FlowJo (Tree Star). Non-specific binding was blocked using unlabeled anti-FcγR

(BD Biosciences). Intracellular Foxp3 expression was assessed using a Foxp3 detection kit (eBioscience). For intracellular staining of cytokines, CD4+CD25+ T cells were stimulated with PMA and ionomycin (10 ng/mL and 0.5 μg/mL, respectively) or anti-CD3 (5 μg/mL) in Brefeldin A (Sigma-Aldrich) buffer prior to mAb staining. Female mice were euthanized 21 days after P3C treatment or LCMV infection, at which point virus was cleared from lymphoid tissue (data not shown). Cell suspensions were prepared from pooled spleens, mesenteric, inguinal, and pancreatic LN of 10–25 mice per group, and CD4+CD25+ T cells were purified as described previously 12. Briefly, CD4+ T cells negatively selected by magnetic separation using sheep anti-rat Dynabeads (Dynal) were stained with biotinylated anti-CD25 mAb, and CD4+CD25+ cells were purified by magnetic separation using anti-streptavidin MACS microbeads (Miltenyi Biotec). Cell purity was measured by flow cytometry and always greater than 95%.

This essential feature of T-cell help, a feature

that ensures help is not given to just any cell (i.e. it increases specificity), is likely to underlie the otherwise paradoxical finding that T-cell helpers to adenovirus do not provide effective helper epitopes for the anti-GUCY2C CD8+ T-cell response. As Snook et al. [18] suggest, the timing of adenoviral antigen and GUCY2C tumor antigen expression is distinct and hence presentation of these antigens will not be linked but rather be presented by different antigen-presenting cells. In terms of the mechanism of tumor elimination, this study supports a central role for CD8+ T cells that have received adequate T-cell help.

CD4+ T cells have also been shown to have a potent PD98059 chemical structure capacity to eliminate tumor cells through perforin/granzyme B or macrophage induction [20] and they can cause substantial collateral tissue damage [21], a capacity that may be of utility in preventing immune escape of malignant cells that have downregulated tumor antigen expression. Although well known for their ability to help CD8+ T cells and B cells, CD4+ T cells can help each other in their activation and differentiation as seen in systems where addition of a foreign helper epitope (e.g. OVA) linked to a second Y-27632 order antigen (e.g. HEL) increases the CD4 response to the second antigen [22, 23]. Nevertheless, in the studies of Snook et al. CD4+ T-cell tolerance to GUCY2C appears to be robust and not easily overcome by additional CD4+ T-cell help. However, should there exist cases where tolerance in CD4+ T cells to a given self/tumor antigen is not complete, provision of foreign helper epitopes could promote their activation, allowing these CD4+ T cells to participate in tumor elimination independent of CD8+ T cells and B cells. Whether cancer vaccines should focus on the promotion of MHC class I- or MHC class II-restricted effector Ceramide glucosyltransferase cells is not necessarily obvious and will require careful dissection of mechanism of

tumor killing generated by the most efficacious vaccines. The benefit of CD8+ T-cell responses is that they may be more self-limiting [17], causing less autoimmune damage. This, however, comes at the potential cost of allowing tumor variants to escape the effector mechanism of destruction. Will provision of foreign helper determinants to cancer vaccines be expected to universally augment tumor immunity? The answer is likely to be no, as exemplified in a study where higher doses of a plasmid encoding a foreign helper epitope in a DNA cancer vaccine reduced vaccine efficacy and survival post tumor challenge [10]. This is consistent with the current study by Snook et al.

Consequently, some ERVs have been positively selected selleck chemicals and maintained in the host genome throughout evolution. This review will focus on the critical role of ERVs in development of the mammalian placenta and specifically highlight the biological role of sheep JSRV-related endogenous betaretroviruses in conceptus (embryo and associated extraembryonic membranes) development. Endogenous retroviruses

(ERVs) are present in the genome of all vertebrates and are vertically transmitted as stable, inherited Mendelian genes.1 ERVs are thought to arise from ancient infections of the germline of the host by exogenous retroviruses. The obligatory integration step of the retroviral replication cycle allowed, during evolution, the incorporation of the viral genome (provirus) into the host genome. Retrotransposition or re-infection of the germline can generate further insertions augmenting the number of ERVs loci in the genome.2 ERVs have heavily colonized the genome of all animal species; for example, they account for approximately 8–10% of the human genome.3 A complete ERV ‘provirus’ (i.e. the retroviral genome integrated into the host cell genome) shares the same genomic structure of an exogenous retrovirus, which is four viral genes (gag, pro, pol, and env) flanked by

two long terminal repeats (LTRs) (Fig. 1). The gag gene encodes for the major viral structural protein, while pro and pol encode for the viral enzymatic machinery necessary for the viral replication cycle. The env gene encodes for the envelope check details glycoprotein (Env) that is inserted into the lipid bilayer of the exterior membrane to form the viral envelope and mediates entry of the virus into susceptible cells. The LTRs contain enhancer and promoter elements that direct expression of the viral genes. Most ERVs are destined to extinction if their expression brings deleterious consequences for the host. Thus, their persistence in the host genome is the result of a fine balance reached throughout evolution

which usually renders them replication defective because of the accumulation of mutations, deletions, rearrangements, and methylation.1 ERVs are widespread throughout vertebrate genomes.4 Some ERVs are highly related to exogenous retroviruses, including Jaagsiekte sheep retrovirus (JSRV), mouse mammary tumor virus, feline leukemia virus, and avian leukemia virus, which are currently active and infect Phosphatidylethanolamine N-methyltransferase sheep, mice, cats, and chickens, respectively.1 These ERVs are generally referred to as ‘modern’ ERVs, because they integrated into the host genome after speciation and are closely related to exogenous viruses that are still infectious, while most ERVs do not have an exogenous counterpart. Some modern ERVs are still able to produce infectious virus because of the lack of inactivating mutations. Modern ERVs can also have insertionally polymorphic loci, because they are not completely fixed in a particular population and are still undergoing endogenization.

1c). As studies of the effects of statins in other experimental models have suggested that the actions of this class of drugs are related to

their anti-proliferative and pro-apoptotic effects on both T cells and tumours, it was important selleck products to rule out that the capacity of simvastatin to induce Foxp3 expression was not secondary to an inhibition of responder T-cell proliferation. However, simvastatin either alone or in combination with TGF-β had only a slight inhibitory effect on the proliferation of CFSE-labelled CD4+ T cells stimulated with anti-CD3/CD28 in our induction cultures (Fig. 1d). Furthermore, the addition of simvastatin did not induce apoptosis and had no effect on the cell cycle of Foxp3− T cells (Fig. S1). Hence, the effects of simvastatin are directly mediated by enhancing the conversion of Foxp3− to Foxp3+ T cells. To address whether Foxp3+ T cells induced in vitro in the presence of simvastatin and TGF-β were suppressive, Foxp3− T cells were isolated from the spleen and lymph nodes of Foxp3gfp mice and activated with plate-bound CD3/CD28 antibody in the presence of TGF-β alone or the combination of simvastatin and TGF-β. The induced GFP+ cells were sorted by FACS, added to Foxp3− responder LGK 974 cells and T-depleted spleen cells as antigen-presenting

cells, and were stimulated with soluble anti-CD3. The Foxp3+ cells induced in the presence of simvastatin/TGF-β were as suppressive as the Foxp3+ T cells induced with TGF-β alone (Fig. 2). The addition of simvastatin therefore did not modulate the function of the induced Foxp3+ T cells. Simvastatin

blocks all downstream pathways of the mevalonate pathway including cholesterol biosynthesis, synthesis of farnesyl bisphosphate, and geranylgeranyl bisphosphate (Fig. 3a). To determine which downstream pathway primarily mediates the synergistic effects of simvastatin on Foxp3 induction, we added simvastatin or downstream pathway-specific inhibitors together with TGF-β to the Foxp3 induction assay (Fig. 3b). As shown above, simvastatin Rebamipide enhanced the induction of Foxp3-expressing cells in the presence of a low concentration of TGF-β. In contrast, the addition of an inhibitor of farnesylation had no effect on the induction of Foxp3 expression whereas the inhibitor of geranylgeranylation mimicked the effects of simvastatin. This result clearly demonstrates that the synergistic effects of simvastatin on the induction of Foxp3 are secondary to inhibition of protein geranylgeranylation. We performed a kinetic study as an initial approach to the analysis of the mechanisms by which simvastatin enhances the induction of Foxp3+ Tregs. When analysed 24 hr after T-cell stimulation, cells cultured with simvastatin alone did not express Foxp3 and no differences were observed, at this time-point between the percentage of Foxp3+ T cells induced by TGF-β and the percentage induced by the combination or TGF-β and simvastatin (Fig. 4a).