“
“To investigate the clinical course and outcome of peritoneal dialysis-associated peritonitis secondary to Gordonia species. We reviewed all Gordonia peritonitis episodes occurring in a single dialysis unit from 1994 to 2013. During the study period, four episodes of Gordonia peritonitis

were recorded. All were male patients. One patient responded to vancomycin therapy. One patient had refractory peritonitis despite vancomycin, but responded to imipenem and amikacin combination therapy. One patient had relapsing peritonitis and required catheter removal. The fourth patient had an elective Tenckhoff catheter exchange. No patient died of peritonitis. Causative organism was not fully identified until 7 to 18 days of peritonitis. Gordonia species is increasingly recognized to cause serious infections. In patients selleck compound undergoing peritoneal dialysis, Gordonia peritonitis should be considered in case of refractory Gram-positive bacilli peritonitis, especially when the exact organism could not be identified one week after the onset of peritonitis. A close liaison with a microbiologist is needed for a timely diagnosis. “
“Chronic cyclosporine (CsA) treatment induces autophagic cell death characterized by excessive autophagosome formation and decreased autophagic clearance. In this study, we

evaluated the influence of ginseng treatment on autophagy in chronic CsA nephropathy. Mice were treated with CsA (30 mg/kg) with or without oxyclozanide Korean red ginseng (KRG) extract (0.2, 0.4 g/kg) CX-4945 cell line for 4 weeks. The effect of KRG on CsA-induced autophagosome formation was measured using phospholipid-conjugated form of LC3-II, beclin-1, and autophagic vacuoles were visualized with electron microscopy. Autophagic clearance was evaluated by accumulation of p62/sequestosome 1 (p62) and ubiquitin, then double immunolabeling for p62 and either LC3-II or ubiquitin. To demonstrate the association between the effects of KRG treatment on autophagy and apoptosis, double immunolabelling for LC3-II and active caspase-3 was performed. Multiple autophagy

pathways were also examined. KRG co-treatment significantly decreased the expression of LC3-II, beclin-1, and the number of autophagic vacuoles compared with the CsA group, and these changes were accompanied by improvements in renal dysfunction and fibrosis. CsA-induced accumulation of p62 and ubiquitin was also decreased by KRG treatment, and these proteins were colocalized with LC3-II and with each other. KRG treatment simultaneously reduced the expression of both active caspase-3 and LC3-II in the injured area. KRG treatment during chronic CsA nephropathy induced the expression of AKT/mTOR, which is a pathway that inhibits autophagy, and reduced AMPK expression. Ginseng treatment attenuated CsA-induced excessive autophagosome formation and autophagic aggregates. These findings suggest that ginseng has a renoprotective effect against CsA-induced autophagic cell death.

The emergence of the epidemics in the East United States, the rapid evolution of host resistance and the persistence of immunologically naïve populations in the West can almost be considered as a natural experiment that might allow to test the following predictions: if the cost of infection is mostly due to the direct damage of the pathogen, then hosts from Arizona

(the nonexposed population) should suffer AG-014699 nmr the most; if immunological resistance incurs costs and these constitutes the bulk of the fitness reduction in infected birds, then exposed (Alabama) hosts should suffer the most. Bonneaud et al. [73] used the same populations of house finches to measure changes in body mass intervening during the first 14 days post-infection as a proxy of infection cost. Overall, birds from the coevolved population lost more body mass than birds from the naïve population, and interestingly, the relationship between bacterial load and loss in body mass was reversed in the two populations (Figure 5a). Whereas bacterial load was negatively correlated with body mass loss in Arizona birds, indicating that most heavily infected birds lost more mass, the sign of the correlation was reversed in Alabama birds. Birds with the lowest bacterial load suffered the most intense mass reduction in Alabama. One possible interpretation of these results PF-02341066 in vivo is that body mass loss represents two different components of the cost of the infection

in the two populations: cost of immunological resistance in Alabama and cost of parasite damage in Arizona. In Isoconazole agreement with this view, the pattern of immune gene expression (indicating a protective immunity) was associated with a higher body mass loss in Alabama than in Arizona (Figure 5b). These results therefore nicely confirm in a more natural setting the findings reported for malaria parasites. Immunological

costs, whatever their nature (energetic or self-reactivity) and whatever the conferred protection (resistance or tolerance), substantially contribute to determine parasite virulence. More recently, Adelman et al. [74] explored explicitly the role played by inflammatory effectors in the resistance/tolerance of house finches experimentally infected with Mycoplasma gallisepticum. They used the same house finch populations (Alabama and Arizona) studied by Bonneaud et al. [71-73], but birds were infected with a strain of Mycoplasma isolated soon after the emergence of the epidemics. They also focused on pro- (IL-1β) and anti-inflammatory (IL-10) effectors as mediators of tolerance to infection. Interestingly, they showed that birds originating from Alabama were more tolerant to the infection (they had a better health for a given pathogen load), even though this depended on the method used to assess tolerance, than birds from Arizona. Birds from Alabama also had a lower expression of the pro-inflammatory cytokine IL-1β.

, 2003). However, recent reports contend that the contribution of homologous

recombination to core diversity in S. aureus may be underestimated (Chan et al., 2011). Nevertheless, mutation is a significant driving force Bafilomycin A1 in S. aureus diversification allowing for evolutionary classification of strains into ST types (see above) (Enright et al., 2000). Most SNPs are within coding regions reflecting the fact that ~ 80% of the core genome encodes protein (Highlander et al., 2007). Synonymous SNPs, those that do not result in amino acid changes, by far outweigh amino acid substituting nonsynonymous SNPs in S. aureus (Herron et al., 2002; Gill et al., 2005; Herron-Olson et al., 2007; Sivaraman & Cole, 2009). This is likely Smoothened Agonist because nonsynonymous mutations are more often detrimental and are therefore subject to evolutionary loss via purifying selection. Consequently, the relative

ratio of nonsynonymous to synonymous substitution rate (dN/dS) among staphylococci is generally less than 1. In contrast, a recent report comparing the complete genome sequences of 10 newly isolated USA300 clones with the published FPRF3757 USA300 sequence revealed an unusually high ratio of nonsynonymous : synonymous SNPs (as high as 2.6 : 1, much higher than reported in comparisons of non-USA300 S. aureus lineages) (Kennedy et al., 2008). This discrepancy can be rationalized by assuming a recent clonal expansion of the USA300 lineage such that new isolates still harbor nonsynonymous SNPs that have not yet undergone purifying selection (Holden et al., 2004). To be sure, the unusually high dN/dS ratio of USA300 (-)-p-Bromotetramisole Oxalate clones is inconsistent with evolutionary convergence among distantly related clones, an event that would only be consistent with normal to low dN/dS ratios if the converging progenitors were of sufficiently diverse origins (Kennedy et al., 2008). It is important to note that overall low dN/dS ratios are not necessarily constant across all functional gene families. For instance, while housekeeping and metabolic genes generally exhibit low dN/dS ratios, genes encoding surface associated or secreted proteins can often

have elevated dN/dS ratios (Jordan et al., 2002; Rocha & Danchin, 2004). This is indicative of forward selective pressures driving variability in these genes either to promote functional differences (e.g. an adhesin adapting to a host receptor molecule) or immune avoidance through changes in antigenicity. Indeed, comparisons among divergent S. aureus clones reveal higher dN/dS ratios for genes encoding components of the cell envelope and secreted proteins than genes encoding housekeeping or metabolic enzymes (Herron et al., 2002; Herron-Olson et al., 2007; Highlander et al., 2007). USA300 clones, however, seem to be an exception to this rule. A recent comparison of genome sequences from USA200, USA300, and a distantly related S.

Since carnitine is reported to inhibit the formation of AGE in vitro, our study suggests that supplementation of carnitine may be a therapeutic target for preventing the accumulation of tissue AGE and subsequently

reducing the risk of CVD in HD patients. “
“Aim:  Health-related quality of life (HRQOL) is decreased in haemodialysis (HD) patients. Irritable bowel syndrome (IBS) is highly prevalent in general population. This study evaluated the prevalence of IBS and its association with HRQOL and depression in HD. Methods:  Sociodemographic and laboratory variables were recorded. Severity of depressive https://www.selleckchem.com/EGFR(HER).html symptoms and HRQOL were assessed by the Beck Depression Inventory (BDI) and Short Form 36 (SF-36), respectively. Diagnosis of IBS was based on Rome II criteria. Results:  Among 236 patients 69 (29.2%) had IBS. Patients with IBS had lower SF-36 scores and had higher depressive symptoms than patients without IBS. Presence of IBS was associated with sleep disturbance (odds ratio (OR) = 2.012; P = 0.045), physical component summary score (OR = 0.963, P = 0.029), mental component summary score (OR = 0.962, P = 0.023), BDI score (OR = 1.040, P = 0.021) and albumin (OR = 0.437, P = 0.01). Conclusion:  IBS is highly prevalent in HD patients. Presence of IBS is closely related with HRQOL

and depression. “
“Although multiple recent studies have confirmed an association between chronic proton-pump inhibitor (PPI)

use and hypomagnesaemia, Staurosporine nmr the physiologic explanation for this association remains uncertain. To address this, we investigated the association GDC 0449 of PPI use with urinary magnesium excretion. We measured 24-hour urine magnesium excretion in collections performed for nephrolithiasis evaluation in 278 consecutive ambulatory patients and determined PPI use from contemporaneous medical records. There were 50 (18%) PPI users at the time of urine collection. The mean daily urinary magnesium was 84.6 ± 42.8 mg in PPI users, compared with 101.2 ± 41.1 mg in non-PPI users (P = 0.01). In adjusted analyses, PPI use was associated with 10.54 ± 5.30 mg/day lower daily urinary magnesium excretion (P = 0.05). Diuretic use did not significantly modify the effect of PPI on urinary magnesium. As a control, PPI use was not associated with other urinary indicators of nutritional intake. Our findings suggest that PPI use is associated with lower 24-hour urine magnesium excretion. Whether this reflects decreased intestinal uptake due to PPI exposure, or residual confounding due to decreased magnesium intake, requires further study. “
“Aim:  The aim of this study was to demonstrate the ability of widely used bioimpedance techniques to assess dry weight (DW) and to predict a state of normal hydration in haemodialysis patients whose post-dialysis weight had been gradually reduced from baseline in successive treatments over time.

Approval for human research was obtained from both the Human JNK signaling inhibitors Investigation Committee at Wayne State University and the Ethics Committee

at the University of Cape Town (UCT) Faculty of Health Sciences. The 107 infants and mothers included in this study of effects on symbolic play are all those for whom complete data were available on the 17 prenatal alcohol exposure, play, and sociodemographic variables examined here. All women who reported drinking during pregnancy were advised to stop or reduce their intake, and all mothers were invited to participate in a home visitor intervention.1 The mother and child were transported by a staff driver and research nurse at 6.5, 12, and 13 months and 5 years buy MK-1775 to our laboratory at the UCT Faculty of Health Sciences, where the maternal interviews and neurobehavioral assessments were performed. At 5 years they were also transported to the FASD diagnostic clinic, which was held at a neighborhood church. Each mother was re-interviewed antenatally and at 1-month postpartum regarding her pregnancy alcohol and drug use. Interviews were conducted in Afrikaans or English,

depending on the mother’s preference. Each mother–infant dyad was provided breakfast prior to the assessments and interviews. All infant assessments were conducted and coded by research staff who were blind with respect to maternal alcohol use and group status; all maternal interviews including the Home Observation for Measurement of the Environment (HOME) were conducted by a developmental pediatrician (C. Liothyronine Sodium D. Molteno) or research staff member who did not observe the infant cognitive or play assessments. In the initial timeline follow-back interview administered at recruitment in the MOU, the mother was asked about her drinking on a day-by-day basis during a typical 2-week period around the time of conception, with recall

linked to specific times of day activities. If her drinking had changed since conception, she was also asked about her drinking during the past 2 weeks and when her drinking had changed. At the follow-up antenatal visit in our laboratory, the mother was asked about her drinking during the previous 2 weeks. If there were any weeks since the recruitment visit when she drank greater quantities, she was asked to report her drinking for those weeks as well. At the 1-month postpartum visit, the mother was asked about her drinking during a typical 2-week period during the latter part of pregnancy, as well as her drinking during any weeks during that period when she drank greater quantities. Volume was recorded for each type of alcohol beverage consumed and converted to oz of AA by using the weights proposed by Bowman, Stein, and Newton (1975; liquor—0.4, beer—0.04, wine—0.2).

1C and D, SARM inhibited both TRIF- and MyD88-mediated AP-1 activation and not just the TRIF-mediated pathway alone. Furthermore, we observed that SARMΔN inhibited the basal AP-1 activity as well, with or without TRIF/MyD88 overexpression (Fig. 1C and D). At this

juncture, it is not apparent which pathway(s) contribute to this basal learn more AP-1 activity. Nevertheless, these observations indicate that SARM-mediated inhibition may not be exclusively directed at TRIF or MyD88, but that SARM may possibly also directly inhibit MAPK phosphorylation. To test whether SARM-mediated AP-1 inhibition was attributable to the suppression of MAPK phosphorylation, we assayed for the phosphorylation of p38 MAPK in HEK293 cells after transfection with SARM alone, or together with TRIF or MyD88. Western blot showed that overexpression of SARM dose-dependently reduced the phosphorylation of p38 regardless of TRIF or MyD88 (Fig. 2), suggesting that SARM inhibits the MAPK pathway independently of TRIF or MyD88. It was reported that SARM inhibits TRIF- but not MyD88-mediated signaling and that SARM–TRIF interaction is responsible for the immune inhibition selleck products by SARM 23. However, our results indicate that in the case of MAPK inhibition, mechanisms other than SARM–TRIF interaction might prevail. These observations are not likely to be attributable to the secondary effect of SARM–TRIF interaction

since SARM suppresses the MyD88- or TRIF-activated MAPK level down to (or even below) the basal level (Figs. 1 and 2). To ensure that our observations of SARM’s inhibitory action are not restricted to the HEK293 cells, we further tested the potential inhibition by SARM of LPS-activated AP-1 in U937 cells, which is a human monocytic cell line. Figure 3A shows that the LPS-induced AP-1 activation in U937 cells was clearly reduced DOCK10 by SARM expression. Two genes downstream of AP-1, collagenase-1 (matrix metalloproteinase-1) 32, 33 and IL-8 were also repressed by SARM (Fig. 3B and C), further supporting SARM’s inhibition of AP-1 activation in U937 cells. To exclude the possibility that our observations were due to artifacts of overexpression, we knocked down

endogenous SARM expression in HEK293 cells using siRNA designated S1, S2 and S3, which target the SAM2, TIR and ARM domains, respectively. Using RT-PCR, we confirmed the suppression of endogenous SARM mRNA in HEK293 cell by all three siRNA (Fig. 4A). Transfection with AP-1 reporter together with any of the siRNA showed that the siRNA abrogated the inhibitory action of SARM, resulting in an increased basal level of AP-1 activation (Fig. 4B). These results strongly support the role of SARM in AP-1 inhibition. Although previous study reported that LPS did not substantially modify SARM mRNA expression 23, we recently observed the horseshoe crab SARM transcription to be dynamically regulated during Gram-negative bacterial infection 20.

DOM-PSMA epitope DNA fusion vaccine or the p.DOM control vaccine. Mice were sacrificed 14 days after receiving a single DNA vaccination and T-cell responses in the spleen were assessed S1P Receptor inhibitor ex vivo by IFN-γ ELISpot assay. All vaccines, including the p.DOM control, were able to prime responses to the p30 MHC class II-binding peptide, an indication of vaccine performance and confirmation of vaccine product integrity (Fig. 1B). Immunization with the respective vaccines additionally induced significant IFN-γ-secreting T cells specific for the PSMA27, PSMA663, and PSMA711 peptides (Fig. 1B). However, the average response

to each vaccine varied, with the p.DOM-PSMA711 vaccine demonstrating the highest response. As expected, immunization with the control p.DOM vaccine failed to induce any PSMA-specific T-cell responses. The peptide sensitivities of the epitope-specific CD8+ T-cell responses

for all vaccines are similar (Fig. 1C). These results indicate that the p.DOM-PSMA27, p.DOM-PSMA663, and p.DOM-PSMA711 vaccines are all able to perform effectively in vivo, allowing the processing of the respective HLA-A*0201 PSMA epitopes from the vaccine backbone in a manner that permits efficient priming of epitope-specific CD8+ Decitabine molecular weight T-cell responses. Vaccination with DNA vaccines encoding an entire antigen provides the potential for the induction of responses specific for more than one CD8+ T-cell epitope and also for the priming of tumor-relevant PSMA-specific CD4+ T-cell responses. To assess the performance of such a vaccine, p.PSMA and p.PSMA-DOM constructs were used. The ability of these vaccines to generate epitope-specific responses against PSMA27, PSMA663, and PSMA711 in HHD mice was assessed by ADAMTS5 ex vivo IFN-γ ELISpot. Mice that

received a single vaccination of either p.PSMA or p.PSMA-DOM were unable to prime detectable responses to any of the three PSMA-derived peptides assessed 14 days later (data not shown). On the contrary, each respective p.DOM-PSMA epitope vaccine effectively primed high levels of peptide-specific CD8+ T cells (Fig. 1B). To attempt to increase PSMA-specific T-cell responses against the full-length PSMA, mice were primed and subsequently boosted with electroporation on day 28 and their responses assessed 8 days later. Despite the fact that p30-specific responses could be detected in all but one of the p.PSMA-DOM-vaccinated mice, there was no significant improvement in the response to any of the candidate peptides induced by either of the full-length vaccines; with only a very low level response to PSMA663 peptide detectable (Fig. 2A). On the contrary, homologous boosting of mice previously immunized with the p.DOM-PSMA663 epitope vaccine resulted in an approximately sixfold increase in peptide-specific T-cell numbers compared with priming (Fig. 2B). Furthermore, this response is approximately 30-fold higher than that seen in mice which received the full-length vaccines.

Vaccine development remains an elusive and coveted breakthrough. Several strategies have been tried over the past 40 years, addressing all stages check details of the life cycle in both whole-organism and recombinant subunit models. The use of radiation-attenuated sporozoites 21 is the only model that has consistently generated reproducible sterilizing immunity in humans and describing it as the “gold standard” of malaria vaccines has become an oft-repeated and

tired but nonetheless accurate phrase in the literature. In this model, sporozoites are subjected to gamma-radiation to cause random genetic mutations, and when injected into mouse and man, accumulate in the host liver, causing resistance to subsequent infections with wild-type parasites; however, despite the similar outcomes of genetically-modified parasite lines, it is debatable whether such whole-organism vaccines can be conceivably manufactured en masse to the market or pass the rigors of safety regulators. Nonethless, people are trying, and Sanaria Inc’s endeavours are ongoing to produce sterile, purified

and cryopreserved radiation-attenuated sporozoites; however, doubts as to the viability of the whole-organism model have paved the way for recombinant subunit vaccines based on immunodominant malarial antigens. One example of this, RTS, S/AS02A, the vaccine based Chk inhibitor on the Plasmodium falciparum circumsporozoite protein, developed by GlaxoSmithKline, has elicited

efficacies ranging from 40 to 60% in Phase III clinical trials and, this is, by all accounts, the best we have so far. Thus in immunology the connection between Plasmodium as a science and malaria as a disease is most apparent, and in the field of vaccinology the link between malaria disease and its impact on the human condition are clearest of all. But can we as basic researchers reconcile the yearly million-fold deaths to the exciting data from our FACS stains and ELISPOTs that will surely ensure that the next paper Fossariinae is accepted by a high-ranking journal? Perhaps some can, some cannot, and for others it does not even matter. All I know is that these two worlds collided quite symbolically for me last December outside the lab, in the form of that unfortunate gentleman in the corridor. The explanation for his condition was that he was presenting himself to the Tropical Medicine clinic of the University Hospital, with whom the research staff share lab and corridor space. Having just returned from a business trip to the Sudan, he was feeling under the weather, feverish, weak and not himself, and decided the best option would be to return to the clinic that had originally given him advice before his travels. Some 15 minutes later, this man was being maneuvered onto a stretcher and treated immediately with intravenous administration of artesunate. We learned later that he had P. falciparum infection with a blood parasitemia of 16%.

The elevations were more modest (<1.5× upper normal Selleck VX 770 values here vs. 2- to 3-fold previously), not associated with symptoms, and not notably dose-related. We speculate that some bacteria may translocate the intestinal wall and be transported systemically, but at too low a level to generate strong systemic immune responses or be detected in blood cultures. No subject receiving BMB54 had abnormal transaminases, suggesting that as demonstrated in vitro (6), this organism may have decreased tropism for hepatic cells in humans. Other published murine studies in which the BMB54 parent strain vs. WT organisms

were injected i.v. showed that transaminases peaked approximately one and four days after intravenous administration, respectively (6). In that study, the BMB54 mutant caused much lower peak transaminase values, likely because of the lack of replication within the liver. After intravenous administration of a prfA-defective L. monocytogenes vaccine strain to humans, 1.5- to 3.5-fold elevations in both GGT and transaminases were reported eight days after administration, but these tests were apparently not performed during days 1 through 7 after i.v. administration (10). No clinical data suggest these transaminase elevations are harbingers of prolonged or serious hepatic dysfunction.

One murine cancer immunotherapy study using an inlB-positive L. monocytogenes Ceritinib ic50 strain exploited this hepatotropism. Hepatic metastases were more efficiently eliminated and survival was prolonged when attenuated L. monocytogenes were used as adjuvant/adjunctive therapy for an irradiated tumor cell vaccine expressing granulocyte-macrophage colony-stimulating factor (36), though that study did not include a comparator strain lacking inlB with decreased

liver tropism. We undertook this study to evaluate the physiological effect of two L. monocytogenes organisms as vectors for delivery of viral antigens. Oral delivery was hoped to stimulate or at least “prime” the mucosal immune system, as many viruses enter through mucosal sites. Bulk IFN-γ ELISpot studies performed on freshly isolated PBMC were chosen as a simple, selleck screening library reproducible measure of systemic cellular immunity increasingly used in studies of viral vaccines. Our earlier human study was limited by a lack of immunological reagents, especially peptide reagents for ELISpots. Here we were able to test synthesized overlapping peptide pools for both listeriolysin and the foreign antigen. A recent study of PBMC derived from approximately 80 healthy human donors showed that bulk IFN-γ ELISpot responses to this same listeriolysin peptide pool also correlated in magnitude and incidence with IL-2 ELISpot responses to the pool (35), so this is likely a reasonable measure of cellular immunogenicity.

Splenocytes were cultured in anti-CD3 coated flat-bottom 96-well plates (0.5 × 106 cells/well) in the presence of increasing concentrations (0–1000 ng/mL) of the immunosuppressive drug MP [15]. For MOG35-55 stimulation, splenocytes were harvested from EAE mice, cultured at 0.5 × 106 cells/well in a U-shape 96-well plates and stimulated with 10 μg/mL MOG35-55. Culture plates were incubated at 37°C in a 5% CO2 atmosphere. After 48 h incubation, supernatants were harvested and stored at −80°C until cytokine analysis. Levels

of IL-2, IFN-γ, IL-4, IL-6, IL-10, IL-1, TNF-α, MCP1, and IL-17A were measured either with a multiplex ELISA kit (Quansys Biosciences, Logan, Utah) or with individual cytokine sandwich ELISA kits (Biolegend, San Diego, CA) as indicated in figure legends and according to manufacturer’s instructions. The immunosuppressive effect of MP is presented as percent of cytokine production without NVP-AUY922 nmr MP. Mice were immunized by subcutaneous injection

into flanks of 100 μg MOG35-55 emulsified in CFA (Difco, Detroit, MI). Pertussis toxin (List Biological Laboratories, Campbell, CA) was injected intraperitoneally (500 ng/mouse) selleck immediately following MOG35-55 injection and again 48 hours later. From day 9 postimmunization, mice were examined daily for clinical signs of the disease and the manifestation of the disease was graded on a 0–5 scale according to the following parameters: 0 = no clinical signs; 0.5 = loss of tail tonus; 1 = tail paralysis; 2 = partial hind-limb paralysis; 3 = hind-limb paralysis; 4 = complete paralysis; 5 = death. All statistical analyses were performed with

GraphPad Prism version 5.02 for Windows (GraphPad Software, San Diego, CA). All variables are expressed as mean ± SEM. p-values were calculated with Student’s t-test or ANOVA test as indicated in figure legends. We thank Dr. Tali Brunner and Prof. Marta Weinstock-Rosin for their valuable comments. We thank Dr. Irit Solodkin for graphical editing the manuscript figures. The Israel Science Foundation and Israel Ministry of Health supported this study. The authors declare no financial or commercial conflict of interest. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized TCL for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Fig. 1. CVS induces anxiety-like behaviors. Anxiety levels were quantified following 24 days of CVS or nonstress conditions. The elevated plus maze (A–B) and open field tests (C) were performed as described in Materials and methods. Bar graphs represent means ± SEM of 20–21 mice in each group, pooled from three independent experiments. p-values were calculated by Student’s t-test. **p < 0.01; ***p < 0.001.