However, further studies must be conducted to clarify the

metabolic changes that occur in the snail host in response to larval nematode infection, to gain a better understanding of the mechanisms involved in this process. This study was supported in part by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio selleck compound de Janeiro (FAPERJ). “
“Ants of the genus Solenopsis occur worldwide, but relatively little is known about their ecology and life history in Brazil, where the genus is highly diverse. Native from South America, ants of the genus Solenopsis (S. invicta and S. richteri) were accidentally introduced in the United States in the beginning of the last century and have become a great public concern, causing damage to the local diversity by displacing native species, and to crops and public health ( Wojcik et al., 2001). Currently, millions of dollars have been spent in the attempt to control them, but despite these efforts, they continue to spread to new Akt inhibitor areas. Solenopsis invicta invasions have also been reported in several countries such as Puerto Rico, New Zealand, and Australia ( Morrison et al., 2004). The potential global range expansion of S. invicta has been correlated with temperature and precipitation, and abrupt variations

of these factors may limit the success of the expansion ( Morrison et al., 2004). Also, the presence of few natural enemies in areas invaded by this ant may be the cause of the abundance of individuals, since in its native range, the opposite scenario is observed. As a result of a fast expansion and interactions with several taxa, many ant species might have acquired several parasites, among them endosymbionts such as Glutathione peroxidase Wolbachia (

Dedeine et al., 2005). Wolbachia (Class Alphaproteobacteria, Order Rickettsiales) are intracellular bacteria inherited from the egg cytoplasm, found in large numbers in the reproductive tissues of many arthropods. Jeyaprakash and Hoy (2000) examined the presence of Wolbachia in 63 species of arthropods and found a frequency of 76%. Extrapolations of these estimates suggest that 106 insect species might be infected, making Wolbachia bacteria among the most widespread parasites of insects ( Dedeine et al., 2005, Hilgenboecker et al., 2008, Shoemaker et al., 2003a and Shoemaker et al., 2003b). Wolbachia variants found in New World ants are more closely related, and differ from other strains found in other insect groups, suggesting they may have become specialized in ants ( Tsutsui et al., 2003). These bacteria can cause reproductive alterations in their hosts to increase transmission to subsequent generations ( Bandi et al., 1998, O’Neill et al., 1992 and Stouthamer et al., 1999).

20 × 0.20 m frame. Samples were taken and treated following standard guidelines for bottom macrofauna sampling (HELCOM 1988). The occurrence and importance of prey items were inferred from the analysis of fish digestive tracts. The former describes the relative frequency of a particular prey in all digestive tracts, while the latter indicates how much

a particular prey item contributes to the total content in a discrete digestive tract. Both parameters were divided into three categories: high, moderate and low. A ‘high’ occurrence means that a particular benthic animal is found in more than 50% of samples, ‘moderate’ – in 20–50% of samples and ‘low ’ in < 20% of samples. A ‘high’ importance means that most of the KU-60019 in vivo digestive tract can be filled with a particular prey species (more than 50% of tract content), ‘moderate’ – 20–50% of tract content, while‘low ’ means that a particular item is only a small addition to the whole tract content (< 20% of tract content). The occurrence and importance of prey items are shown in Table 1. As the study aimed to evaluate the quality of the seabed for the feeding of fish, the assessment was based only on benthic invertebrates, excluding nectobenthic species and small pelagic fish. To predict the biomass selleck products distribution of prey species the Random forests (RF) regression

model (Breiman 2001) implemented in the ‘randomForest 4.6-2’ package (Liaw & Wiener 2002) within the R environment was chosen. The modelling procedure was as follows. First of all, a correlation matrix was created for all predictors. If a correlation coefficient was > 0.7 or the VIF (variance inflation factors) were > 3, those predictors were not used for constructing

the model. Then the biomass data were split into two sets: train data (70% of all data) for constructing the model and test data (the remaining 30%) for validation. In order to avoid an uneven distribution of zero values the split was made semi-randomly: all sites were chosen randomly but with the proviso that sites with zero values would distribute 70/30 in train/test datasets. Parameters for Org 27569 RF were selected as follows: the number of trees (ntree) was set to 1000, while the number of variables randomly selected at each node (mtry) and minimum node size (ndsize) were set to default values 2.3 and 5 respectively. After running the model the importance of the predictors was assessed. The Mean Decrease Accuracy (%IncMSE) was calculated to assess the importance of every environmental factor for the response variable. During validation, predicted values were compared with observations of external data (test dataset), thereby revealing the model’s true performance. Several estimates were calculated: (1) MAD – mean absolute deviation, (2) CVMAD – coefficient of variation of MAD, rs – Spearman’s correlation between observed (yt  ) and predicted ( y^t) values. equation(1) MAD=n−1∑t=1nyt−y^t, equation(2) CVMAD=ΜADy¯×100.

Removing MVPA from the models did not substantially change the coefficients and all models were unaffected by replacement of BMI for waist

circumference. No associations between MVPA and markers of inflammation were observed following adjustment for confounders. Changes in sedentary time and inflammatory markers between baseline and 6 months are shown in Table 1. Sedentary time was reduced in women only, decreasing by 0.4 ± 1.2 h per day between baseline and 6 months. In women, sICAM-1 had reduced by 7.9% (95% CI −14.3, −1.1) after 6 months and reductions of 42.0% (95% CI −56.9, −22.1) in CRP were also seen. In selleck chemicals men, the only inflammatory cytokine to change was adiponectin increasing by 23.6% (95% CI 12.4, 36.0) after 6 months. Daily MVPA increased by 3.8 ± 22.9 min between baseline and follow-up in men, while no changes were seen in women. Table 3 shows the longitudinal associations between sedentary time and inflammatory outcomes at follow-up. A change in sedentary time from baseline to 6 months predicted CRP at follow-up in women, with

a reduction of 1 h selleck in sedentary time being associated with a 24% (95% CI 1.0, 48.0) reduction in CRP in women, with no associations seen in men. Regression models containing appropriate interaction terms provided some evidence that any associations between sedentary time and CRP differed for men and women (Table 2). There was also evidence of an interaction by sex for the relationship between

a change in sedentary time and CRP (Table 3). All results were unaffected if participants with a CRP >10 mg/L (n = 17) were excluded from the analysis, data not shown. This study investigated the cross-sectional and longitudinal check associations between total sedentary time and markers of inflammation in a sample of adults with newly diagnosed type 2 diabetes enrolled in the Early ACTID diet and lifestyle randomised controlled trial. Independent cross-sectional associations between total sedentary time and IL-6 were seen in men and women; however, all associations were attenuated following adjustment for waist circumference. At 6 months follow-up, adiponectin had increased in men compared to baseline and sICAM-1 and CRP were reduced in women. Lifestyle behaviours were also changed with men increasing MVPA and women reducing sedentary time. Longitudinal associations were demonstrated between a change in sedentary time and follow-up CRP in women. All associations were independent of MVPA. Our results build on accumulating evidence to show the detrimental health effects of prolonged sedentary time [15] and [18]. To our knowledge, these results are the first to show the harmful effects of sedentary time on inflammation in adults with newly diagnosed type 2 diabetes. This study has several strengths. The study included a relatively large number of adults with newly diagnosed type 2 diabetes.

, 2011; http://www.tractor-mri.org.uk). Independent sample t-tests indicated that the 90 participants in the current study did not differ significantly from the other participants that attended wave 2 of LBC1936 testing for LM1 [t (862) = −1.15, p = .25], LM2 [t (862) = −1.31, p = .19], VPAI [t (843) = −1.20, p = .23] and VPAII [t (841) = −1.40, p = .16]. Pearson’s correlations with large effect sizes between tests for scores of immediate [LM1 and VPA1; r (87) = .56,

p < .001] and delayed recall [LMII and VPAII; r (87) = .50, p < .001] suggested that the test scores Compound C could be combined into two overall measures. Z-scores were created and averaged to yield two scores of verbal memory ability for each participant; one of Immediate see more (M = −.01, SD = .90) and one of Delayed recall ability (M = −.01, SD = .89). One participant did not complete the VPA, and so the score for LM performance was used in place of an average verbal memory ability score. Correlations among raw memory scores are given in Supplementary Table I. All regional volumes were controlled for intracranial volume (ICV; reflecting

maximal healthy brain size; Royle et al., 2013). As such, residuals derived from the linear regression between ICV and regional volume allow us to compare volumes across individuals, accounting for how large one would expect them to be given their maximal healthy brain size. Thus, two individuals with the same raw IFG volume (for example) are not necessarily treated the same; rather, the corrected value represents its actual size relative to its expected size within the sample. Though this is an imperfect measure that cannot take account of individual differences in the degree of tissue-specific change

(for which longitudinal data MycoClean Mycoplasma Removal Kit are required), we contend that – particularly in the context of older participants – this step is preferable to using raw values, which cannot differentiate at all between participants with different levels of global atrophy. The resultant unstandardized residuals were used in all further analysis. Outlier (±3 SD) and normality checks were performed on all variables. The object maps of the outlying values were inspected (without knowledge of their relation to other variables) to check for measurement error. A single marginal outlier was identified in both left and right hippocampi, and they were winsorized following examination of object maps by one of the authors (NAR) in order to preserve data points but minimize the disproportionate effect of outlying points on parametric analyses. Tract segmentation quality was examined by one of the authors (SMM).

Because TGF-β can induce expression of CD103 in some cells, 14 a potential explanation for the reduced ability of Itgb8 (CD11c-Cre) mice to induce iTregs is that lower CD103+ DC numbers are present in these mice owing to reduced TGF-β activation. However, we found that Itgb8 (CD11c-Cre) mice had comparable numbers of CD103+ DCs in all gut-associated www.selleckchem.com/products/nivolumab.html lymphoid tissue examined ( Figure 6C). Taken together with our in vitro data, these results strongly indicate that αvβ8-mediated TGF-β activation by specialized intestinal

CD103+ DCs is essential for the induction of tolerogenic Foxp3+ iTregs in the gut. Intestinal CD103+ DCs have emerged as key cells in maintaining gut tolerance, with recent data showing that these cells have the enhanced ability to induce gut-homing receptors on responding T cells15 and convert naïve T cells to immune-suppressive Foxp3+ iTregs.6 and 7 These important functions appear to be due to high expression of the retinal dehydrogenase aldh1a2 in CD103+ intestinal DCs, suggesting they have the capacity to metabolize retinal acid to RA. 6 However, our data now show that CD103+ gut DCs have an enhanced ability to induce iTregs that is independent of RA but completely selleck screening library dependent on TGF-β function. These results strongly suggest that the enhanced ability of CD103+

intestinal DCs to induce iTregs is linked to an increased ability of these cells to produce active TGF-β. Indeed, we directly show for the first time that CD103+ intestinal

DCs are specialized to activate latent TGF-β and that elevated expression of the TGF-β–activating integrin αvβ8 by CD103+ intestinal DCs is responsible for the enhanced ability of these cells to activate latent TGF-β. Importantly, elevated integrin αvβ8-mediated TGF-β activation by CD103+ intestinal DCs is responsible for their increased ability to induce Foxp3+ Tregs both in vitro and in vivo. We have therefore identified a novel molecular pathway by which a specialized gut DC subset activates TGF-β to promote a tolerogenic environment via induction of Foxp3+ iTregs. Many different immune cells produce TGF-β (predominately the isoform TGF-β116) Morin Hydrate but always noncovalently bound to an N-terminal propeptide (LAP), preventing TGF-β binding to its receptor.8 Hence, TGF-β function is exquisitely regulated at the level of TGF-β activation. Strong evidence in vivo now supports a critical role for integrin receptors in activating latent TGF-β1 via interaction with an RGD integrin binding motif present in the LAP region of the latent complex.17 Our finding that the TGF-β–activating integrin αvβ8 is highly expressed and functionally important on specialized tolerogenic DCs in the intestine correlates with our previous findings that Itgb8 (CD11c-Cre) mice develop severe colitis associated with reduced levels of total Foxp3+ Tregs in the colonic lamina propria.

The benign bronchioloalveolar adenomas Omipalisib cost appeared as a solid focal area of increased cellularity obliterating the underlying alveolar architecture. Adenomas did not imitate the alveolar structure and formed glandular, papillary, or solid structures. They were embedded as single islands in hyperplastic areas or appeared

as solid nodules sharply demarcated and compressing the adjacent lung tissue. A mild cellular atypia and single mitotic figures were observed. Malignant bronchioloalveolar carcinomas appeared as well demarcated areas of increased cellularity with a papillary or solitary morphology embedded in adenomatous tissue. In contrast to adenomas, a higher degree of pleomorphism and anaplasia of the cells was indicative for malignancy. Malignant cells appeared as single foci embedded in poorly differentiated areas or formed Volasertib in vitro confluent lesions. The progression from adenomas to carcinomas appeared to be transient and discrimination was sometimes difficult. After 10 months of MS inhalation, no clear tumorigenic effect was observed (Table 3). A statistically significant 3-fold increase in adenoma multiplicity was observed in the

male MS-150 group, but this may be a chance finding as there was no concentration/response relationship and no parallel finding in the female mouse groups. This lack of a tumorigenic effect at 10 months of MS inhalation is in general agreement with the previous findings in Study 1 (Stinn et al., 2012). After 18 months of MS inhalation, a clear tumorigenic effect was observed (Table 3). Similar to Study 1, the level of hyperplasia remained relatively low regardless of air or MS exposure Carnitine dehydrogenase which in view of the increased tumor levels would suggest that this is a transient preneoplastic finding during

mouse lung tumorigenesis. The incidence and multiplicity of pulmonary adenomas and carcinomas increased in an MS concentration-dependent manner. For some of the proliferation parameters, statistically significant differences were obtained between individual MS concentration levels. The most robust and differentiating parameter seemed to be the combined multiplicity of adenomas and carcinomas, because all MS concentrations could be statistically significantly differentiated except between MS-75 and sham control groups. The increases in tumor multiplicity relative to sham were very similar to those observed for male mice in the previous Study 1 (Stinn et al., 2012) (Fig. 3). In general, the MS-induced tumorigenic effect was more pronounced for adenomas than for carcinomas (Table 3, Fig. 3). This resulted in a lower proportion of carcinomas relative to both tumors types in MS- compared to sham-exposed mice (41, 36, 24, and 23% for males and 37, 33, 14, and 29% for females in sham, MS-75, MS-150, and MS-300 groups, respectively), which in contrast to the previous Study 1 (Stinn et al., 2012) was not statistically significant in the current study.

The glucagon stimulation test was performed in fasted rats and no significant difference was observed between fasted TGR and SD rats. However, this result can be attributed to the action of glucagon in all the metabolic sensitive tissues of the rat (such as muscle) and not exclusively in the liver. Glycogenolysis was evaluated through baseline hepatic glycogen concentration and levels of hepatic glycogen phosphorylase, an allosteric enzyme responsible for catalyzing the phosphorylation of glycogen to glucose1-P, playing a fundamental role in glycogen SP600125 chemical structure metabolism [7] and [26]. There was no significant

difference in hepatic glycogen phosphorylase levels analyzed by Western blotting. The absence of alteration in glycogenolysis pathway can explain the unaltered hepatic glycogen levels in TGR. To evaluate gluconeogenesis pathway separately we performed the pyruvate challenge test [18]. The first regulated step in the gluconeogenic pathway from pyruvate and its precursors is the pyruvate to oxaloacetate carboxylation, catalyzed by ATP-dependent pyruvate carboxylase [8], [9] and [10]. The pyruvate challenge experiment showed

that overnight fasted TGR rats have a decrease in buy AZD2281 the glucose synthesis when compared to overnight fasted SD rats, suggesting a downregulation in the gluconeogenesis pathway, since overnight fasted rats have negligible amounts of preformed glycogen. In order to confirm the downregulation of the gluconeogenesis pathway, it was evaluated the mRNA expression of the key enzymes of this route. The expression of G6Pase, a multicomponent enzyme system that hydrolyses glucose-6-phospate (G6P) to glucose in the final step of gluconeogenesis, showed no statistically difference in TGR and SD rats. PEPCK, one of the main rate-limiting enzymes of gluconeogenesis, simultaneously decarboxilates and phosphorylates oxaloacetate to phosphoenolpyruvate, had its expression significantly reduced in TGR when compared to SD rats. These results suggest that the gluconeogenesis downregulation could be due to the decreased expression of PEPCK. Recently, it has been documented that HNF4α has been implicated in gluconeogenesis through transcriptional

regulation of G6Pase and PEPCK, which are before rate-limiting enzymes in this process as discussed previously [27]. The mRNA expression of HNF4α analysis by RT-PCR showed significantly decreased levels in TGR, when compared to SD rats. This finding pointed out to a relation between Ang-(1-7) and HNF4α, leading to an overall downregulation of gluconeogenesis. This result can be responsible, at least in part, for the improved circulating glycemic profile in TGR described previously [23]. In summary, the results obtained in the present study show that transgenic rats with increased Ang-(1-7) plasma levels, present a lower activation of the gluconeogenesis pathway responsible for glucose synthesis, without evidence of alteration in the hepatic glycogenolysis.

Thus the SNAP and FT-based methods would seem to have a variety of applications. A malfunction of regulatory degradation may result in some renal, cardiovascular, and neuronal diseases. The application of our methods in animal models will be useful to elucidate this possibility. The cDNA for mouse Kir2.1 was generously provided by Dr L.Y. Jan (Kubo et al., 1993). The cDNA for SNAP, which

is BGJ398 the mutant of the O6-alkylguanine-DNA alkyltransferase, and FT were purchased from NEB (Ipswich, MA) and Clontech (Mountain View, CA), respectively. The plasmids which express Kv1.4 and Kv2.1 were donated by Dr. Nerbonne (Washington University, St. Louis, MO). phrGFP-II, which expresses only GFP, was purchased from Stratagene (La Jolla, CA). SNAP-Kir and FT-Kir were constructed by PCR and the nucleotide sequences were checked thereafter. The SNAP-Kir2.1 gene was then cloned into pSVL (GE Healthcare, Little

Chalfont, Buckinghamshire, UK) and CSII-CMV-MCS PF-562271 molecular weight (donated from Dr. Miyoshi, Riken, Ibaraki, Japan). For the dominant-negative form of Kir2.1, the signature sequence GYG (143–145) was mutated to AAA by PCR. The E224G mutation was also introduced by PCR. The mutated SNAP-Kir2.1 genes were introduced to CSII-CMV-MCS. The plasmids were transfected into 293T cells (purchased from RIKEN BioResource Center, Ibaraki, Japan) with the calcium-phosphate method. Plasmids (3 μg) dissolved in 150 μl of 0.25 M CaCl2 was added to equal volume of 2× HBS, and the mixture was added to the 35 mm dish. The cells were washed twice with PBS 5 h after and incubated at 37 °C for up to 72 h in the presence or absence of

0.3 mM BaCl2 dissolved in the medium. The FT-Kir2.1 was expressed by pcDNA3.1 plasmid containing CMV promoter (Invitrogen, Carlsbad, CA). The lentiviral vector for SNAP-Kir2.1 was prepared as described previously (Okada and Matsuda, 2008). The Moloney retroviral vector for FT-Kir2.1 was prepared as described previously (Lin et al., 2010). Using these viral vectors, we established the 142-3 and 116-5 cell line with the limited dilution of infected 293T cells. The 293T cells were cultivated in DMEM containing 10% FBS and pencillin/streptomycin. SNAP-Kir2.1 was pulse-labeled with tuclazepam SNAP-cell-TMR-Star (2 μM) dissolved in DMEM for 45 min at 37 °C. The cells were washed twice with PBS, and further incubated in the medium for 2 h or more at 37 °C. For the confocal microscopic analysis, the 293T cells, cultivated in 35 mm dish, were fixed with 4% paraformaldehyde for 30 min at room temperature and washed with PBS. Then a coverslip was mounted with a drop of Fluoromount (Sigma, St. Louis, MO). The single plane images were taken with a confocal microscope (FV300, Olympus, Tokyo, Japan). The dichroic filter used for SNAP-Kir2.1 was rhodamine-phalloidin. Those used for FT-Kir2.1 were EGFP and Texas-red.

At the concentrations tested (5–25 μM), ABA inhibited state-3 respiration of mitochondria in a concentration-dependent manner. This effect was observed when mitochondria were energized with either glutamate plus malate, the respiratory chain site I substrates (Fig. 2A), or succinate, a respiratory chain site II substrate (Fig. 2B). A maximum effect was observed at a concentration of 15 μM. ABA also inhibited

state-3 respiration of TMPD plus ascorbate-energized mitochondria in a concentration-dependent manner (data not shown). The compound did not stimulate state-4 respiration, indicating that it does not act as an uncoupler (data not shown). Subsequent experiments with carbonyl cyanide m-chlorophenyl hydrazone (CCCP)-stimulated mitochondrial respiration were performed to test check details the inhibitor effect of the compound on the respiratory chain or on ATP synthase. ABA did not inhibit CCCP-uncoupled respiration, indicating that only oxidative phosphorylation was inhibited (Fig. 3). The same behavior was observed with oligomycin (ATPase inhibitor) and carboxyatractyloside

(ANT inhibitor). Figure 4 shows the effect of ABA on the Δψ of glutamate + malate-energized rat liver mitochondria. ABA (25 μM) did not dissipate Δψ. The same behavior was observed for oligomycin and carboxyatractyloside. At the end of the experiment, 1 μM CCCP (uncoupler) or 2.5 μM rotenone (complex I inhibitor) was added as a positive control, and the mitochondrial membrane electrical potential dissipated. The effect of ABA on click here mitochondrial ATP levels was evaluated using the respiratory assay conditions 15 min after mitochondria were incubated with the compound (Fig. 5). In agreement with the mitochondrial respiration results, ABA caused a significant concentration-dependent

decrease in mitochondrial ATP levels, reaching a maximum effect at 15 μM. The effects of Proteasome inhibitor ABA on FoF1-ATPase activity were measured in intact-uncoupled mitochondria in the presence of CCCP, and in freeze–thawing-disrupted mitochondria, as shown in Fig. 6A and B, respectively. The ATPase activity of uncoupled mitochondria was increased in a concentration-dependent manner by ABA (Fig. 6A). In disrupted mitochondria, the effects were less dramatic and similar across all concentrations tested (Fig. 6B). The effect of ABA on NADH and succinate dehydrogenase activity was measured in freeze–thawing-disrupted mitochondria. As expected, ABA at concentrations from 5 to 25 μM did not cause significant changes in enzyme activity (data not shown). The purpose of this assay was to determine whether ABA inhibits ADP-induced depolarization of Δψ by interference with ANT. Carboxyatractyloside was used as a positive control for direct ANT inhibition. ABA caused significant, concentration-dependent inhibition of ADP-stimulated depolarization of Δψ (Fig. 7).

In clinical oncology, breast cancers are categorized on the basis of hormone receptors [estrogen (ER) and progesterone

(PR)] and amplification of the oncogene Her2. These categories determine prognosis and treatment options [40]. We analyzed expression of CXCL12, CXCR4, and CXCR7 and individual isoforms in tumors positive for both ER and PR, Her2 only, and all three receptors (triple positive), as well as primary cancers lacking expression of these three receptors (triple negative). Gene-level expression of CXCL12 and the α and β isoforms each varied significantly Venetoclax across these subtypes with highest amounts in ER/PR positive and triple positive cancers ( Figure 3A). By comparison, levels of overall CXCL12, CXCL12-α, and CXCL12-β decreased in triple negative cancer and to an even greater extent in Her2 positive tumors. Other isoforms of CXCL12 did not vary significantly with receptor status. CXCR7 varied with receptor status in a pattern comparable to CXCL12 ( Figure 3A). Levels of CXCR7 were highest in ER/PR positive and triple positive tumors with lower expression in triple negative and Her2 positive cancers. Interestingly, we identified a distinct pattern of expression for CXCR4, which was elevated

in triple negative breast cancer relative to the other groups [41]. More recently, breast cancers have been classified into intrinsic molecular subtypes (Normal-like, Luminal A, Luminal B, Her2-enriched, and Basal-like) defined by a 50-gene Navitoclax nmr panel referred to as PAM50. click here Intrinsic subtypes add prognostic and predictive information to standard metrics used to categorize breast cancer. When analyzed across intrinsic subtypes, CXCL12 and its α, β, and γ isoforms varied significantly ( Figure 3B). Expression was highest in the Normal-like cluster, which is consistent with our data in Figure 1A showing up-regulation of these isoforms in normal samples.

Luminal A had the next highest expression with Luminal B, Her2-enriched, and Basal clusters exhibiting lower expression. We also identified significant variations of receptors with intrinsic subtypes of breast cancer. CXCR4 showed differential expression among clusters with lowest levels in Luminal A and Luminal B subtypes and highest expression in Basal cancers. By comparison, levels of CXCR7 were highest in Luminal A and Luminal B subtypes. CXCL12 and its α, β, and γ isoforms vary significantly with race. We identified higher expression in whites than Asians or African-Americans ( Figure W1A). Gene-level CXCL12 and the α isoform also changed significantly by age group with levels peaking in the 50 to 60 year age group relative to younger or older patients ( Figure W1B). CXCL12-β and -γ showed a similar pattern across age groups, although differences were not significant. We did not identify significant correlations for race or age groups for CXCR4 or CXCR7.