There is an urgent need to investigate whether or not accumulations of CTL escape mutations at a population level increase the virulence of HIV-1 infection. In the present study, we have examined the impact of HLA class I allele expression on the level of pVL and rate of CD4+ T cell decline in

chronically HIV-1 infected Japanese patients who have distinct class I allele expression profiles compared to Caucasians or Africans, in that: (1) they selleck compound express neither major protective alleles (HLA-B27/B57) nor detrimental alleles (HLA-B*3502/B*3503/B53); and (2) they have a much narrower HLA distribution as represented by around 70% of Japanese people expressing HLA-A24 (18), and thereby

likely facilitate accumulation of CTL escape mutations at the population level. In a cross-sectional analysis, we found no significant associations between the level of pVL and individual HLA PI3K inhibitor class I allele expression in this unique Asian population, including HLA-B51 which ranked as the third most protective allele in Caucasians (7). Further analysis revealed that HLA-B51 has been losing its ability to control viremia in this population as the epidemic matures. However this is not the case for the other alleles, suggesting that unfavorable consequences of the accumulation of CTL escape mutations might be limited to particular HLA class I alleles. Nonetheless, these differences still pose a significant challenge for those designing globally effective HIV vaccines. In the present study, a total of 141 Japanese subjects who had been diagnosed with HIV-1 infection from 1995 to 2007, and had remained untreated, were enrolled. Dimethyl sulfoxide In order to exclude individuals diagnosed during an acute/early phase of infection, only those who were fully Western blot positive were enrolled, while those with a history of being HIV seronegative

within the year prior to their first visit to the clinics were excluded. Written informed consent was obtained from all participants, and the study was approved by the Institutional Review Boards of the Institute of Medical Science, the University of Tokyo (No. 11-2-0329). All the participants were Japanese and all had acquired HIV-1 through sexual intercourse; all but six were men, 96% of whom were MSM. PVL were measured by the Roche HIV Amplicore (Roche Diagnostics, Indianapolis, IN, USA). PVL and CD4+ T cell counts at the first available time points were used for the analyses. The median pVL was 19 000 RNA copies/ml (IQR: 5000–49 000 RNA copies/ml). The median CD4+T cell count was 351/μl (IQR: 273–444/μl) at the corresponding time point for each individual. The rates of decline in CD4+ T cell count (cells/year) were calculated using the values at 6 and 18 months after the first visit to the hospital.

In order to understand more clearly the gene transcriptional profiles associated AZD4547 purchase with CsA treatment in OS patients, 90 genes related to the immune system were examined by TLDA before and after successful treatment (patient

1). After treatment, 26·6% (24 of 90) of genes showed an expression level of more than twofold increase or decrease compared with the patient’s baseline gene expression (Fig. 4). Of these, the expression of 11 genes (12·2%) was down-regulated (by a factor of 2·3–5·2, values of 0·44–0·19, respectively, in Fig. 4, and 13 genes (14·4%) were up-regulated (by a factor of 2·04–19). The expression of several genes that are known to be down-regulated by CsA therapy such as IL-2 and Fas ligand DZNeP mw (FasL) were found to be low (0·197- and 0·32-fold decrease). Interestingly, several genes that are known to be involved in immune regulation and autoimmunity were found to be markedly up-regulated

[e.g. IL-10, intercellular adhesion molecule (ICAM) 1 and transforming growth factor (TGF)-β] or down-regulated (e.g. CCR4 and CCR5). The immunological hallmark of OS is the expansion and activation of an oligoclonal population of autoreactive T cells. We have already shown that, in OS, similar T cell expansions are found in peripheral blood and in target organs (e.g. skin) [12]. These cells should be controlled rapidly by immunosuppressive agents to avoid tissue infiltration and to improve the general outcome of OS patients [14]. Here we describe a selective immune response to such treatments in patients with Omenn phenotype. Diverse topical and systemic immunosuppressive

therapies have been shown to be useful in OS patients. Many use CsA as the gold standard treatment for these patients. Alternatively, tacrolimus (FK506) is used. Despite similarity in their accepted mode of action, they alter T cell receptor expression differentially in vivo, therefore can have different effects on OS patients [15]. Failure of treatment Galeterone sometimes requires alternative or a combination of therapies [16]. Herein, we report on two patients; the first patient responded to CsA treatment while the second patient did not. Surprisingly, the initial expanded oligoclonal autoreactive clone (TCR-Vβ 17) in the latter patient responded well to CsA treatment, but other TCR-Vβs had started to expand, probably causing the patient’s unremitting autoimmune symptoms. Many unknown environmental and/or host factors can produce expanded lymphocytes in OS. In some cases the trigger (e.g. infection) that exacerbates the autoreactive process is found [17]. Patient 2 underwent a thorough infectious work-up, which was found to be negative, and no other obvious factor to trigger his symptoms could be detected to explain the presence of new TCR clones. However, expansion of certain new TCR-Vβ clones may also represent not only pathogen exposure, but also skewing towards self-antigens and autoimmunity [9].

8 Previous studies have

revealed that inflammatory mediators BMN 673 molecular weight influence the apoptosis of inflammatory cells.9,10 However, the literature concerning the effect of inflammatory modulators on phagocytic clearance of apoptotic cells is limited and contains discrepancies. For example, TNF-α, a key pro-inflammatory factor that is up-regulated at inflammatory sites, has been reported previously to enhance the uptake of apoptotic cells by immature monocyte-derived macrophages.11 Another study demonstrated that TNF-α inhibits the phagocytosis of apoptotic cells by mature macrophages.12 A recent study indicated that the uptake of apoptotic neutrophils by human monocyte-derived macrophages was negatively regulated by TNF-α, which was opposite to the effect of the anti-inflammatory factor interleukin (IL)-10.13 Growth arrest-specific gene 6 (Gas6) is an anti-inflammatory factor.14,15 Gas6 and its receptors – Tyro3, Axl and Mer (TAM) receptor tyrosine kinases– are broadly expressed in various types of phagocyte. The activation of TAM receptors by Gas6 inhibits inflammation responses and promotes the phagocytosis of apoptotic cells by phagocytes.16 In the present study, we found that LPS specifically inhibited mouse macrophage uptake of apoptotic neutrophils through suppression

of Gas6 and induction of TNF-α in an autocrine manner. The findings provide novel insights into the effect of inflammatory modulators on phagocytic clearance of

apoptotic cells by macrophages. C57BL/6J mice were Trametinib mw purchased from the Laboratory Animal Center of Peking Union Medical College (Beijing, China). Toll-like receptor 4 (TLR4) mutant C57BL/10ScN mice (Cat. 003752) were AMP deaminase purchased from Jackson Laboratories (Bar Harbor, ME). The animals were housed under specific pathogen-free conditions with a 12-hr light/dark cycle and had free access to food and water. The mice were maintained and treated in accordance with the guidelines for the care and use of laboratory animals established by the Chinese Council on Animal Care. Mice 8–10 weeks old were used in this study. Ultrapure LPS (Escherichia coli 0111:B4) was obtained from InvivoGen (San Diego, CA), and no detectable TNF was produced in TLR4-null (TLR4−/−) macrophages in response to this LPS. TNF-α and neutralizing antibodies against TNF-α were obtained from PeproTech Inc. (Rocky Hill, NJ). Gas6 and neutralizing antibodies against Gas6 were obtained from R & D Systems (Minneapolis, MN). Peritoneal macrophages were collected from peritoneal fluid as previously described.17 Briefly, mice were anaesthetized with CO2 and then killed by cervical dislocation. The peritoneal cavities were lavaged with 5 ml of cold phosphate-buffered saline (PBS) to collect peritoneal cells. The cells were seeded at 4 × 105 cells/well into a 24-well plate with RPMI-1640 medium (Gibco-BRL, Grand Island, NY) containing 10% fetal calf serum (FCS; Gibco-BRL).

Before performance of DGGE, the PCR products were analyzed by electrophoresis on a 1.7% agarose gel containing 0.5 μg/ml ethidium bromide to confirm

equal loading of the samples (data not shown). The conditions of DGGE and the visualization of the gels were the same as above. Phoretix 1D software package (Nonlinear Dynamics, Newcastle, United Kingdom) elimination followed by manual correction was performed to create a synthetic reference lane for each gel. Each lane on the gel was then compared to the reference lane, allowing generation of a matching profile for each lane (Fig. 2). UPGMA dendrograms were then used to generate the clustering patterns shown Cilomilast datasheet in Figure 2 (14). For a single sample, the number of bands on DGGE gel ranged from 23–47 for the V3-V5 region and 20–49 for the V6-V8 region without significant differences (P > 0.05), although there was a trend towards the average numbers in the V6-V8 region being higher than for the V3-V5 region (Fig. 3a). In samples from the same periodontal pockets, there were no significant differences in the number of bands at the baseline and 6 weeks after mechanical debridement in either Stem Cell Compound Library purchase the V3-V5 or V6-V8 regions (P > 0.05, Fig. 3a), suggesting that re-colonization of bacteria may indeed occur, as reported by Zijnge et

al. (7). These authors analyzed the BCKDHA DGGE fingerprints of the microbial population from four patients at baseline, one day after treatment and 3 months after treatment (7). They observed that two patients showed a pronounced decrease in the DGGE bands one day after treatment, but that by 3 months after treatment the number of the bands had increased back to the baseline level. In addition, in that report the Cs of the DGGE profiles of the four patients was 33–47% between baseline and 3 month after treatment. The Cs

of the DGGE profiles of the six patients in the present research was also calculated by the same method using the following equation: (7) DGGE analysis has been thought to be a good alternative in periodontal microbial diagnostics (7, 8, 14). However, the comparability of plaque bacterial DGGE patterns generated by different primer pairs remains unclear. To elucidate which region can best be used to characterize subgingival communities by DGGE, type strains of periodontal pathogens of P. gingivalis, F. nucleatium and P. nigrascens were used in the present study to generate 16S rDNA fragments of V3, V3-V5, and V6-V8 regions. From the present results, the authors speculate that the primer pairs of V3-s and V3-a, which target the DNA fragment in Escherichia coli 16S RNA between positions 341 to 534, may make it difficult to estimate the bacterial population, since multiple bands for single pathogenic bacteria appeared in the lanes.

Therefore, we aim to investigate the

role of Sirt1 in diabetic nephropathy (DN). Methods and Results: We found that Sirt1 in proximal tubules (PTs) was downregulated before albuminuria, and, thereafter, Sirt1 in podocytes (Pods) was downregulated in DN mice including both streptozotocin-induced and obese (db/db) mice. Then, we created PT-specific Sirt1 transgenic (Tg) and conditional knockout (CKO) mice to examine the role of PT’s Sirt1. Sirt1 Tg prevented and CKO aggravated glomerular changes and albuminuria that occured in diabetes, respectively. Non-diabetic CKO mice exhibited albuminuria, suggesting that Sirt1 in PTs affects glomerular function. We also observed that reduced PT’s Sirt1 in DN decreased selleck chemical NMN (Nicotinamide Mono Nucleotide, a key intermediate of Sirt1-related nicotinic acid metabolism) led to decreasing Pod’s Sirt1. Reduced Sirt1 increased Claudin-1, a tight junction protein, in Pods by an epigenetic mechanism whereby decreased Pod’s Sirt1 inactivated

Dnmt1 leading to reduced CpG methylation of Claudin-1 gene, which contributed to increased Claudin-1 expression and albuminuria. Intriguingly, Claudins are generally known to strengthen the epithelial barrier, but we novely showed that overexpression of Claudin-1 in Pods increased glomerular permeability by activating β-catenin–Snail pathway. We also demonstrated retrograde interplay from PTs to Pods mediated by NMN by analyzing Hydroxychloroquine conditioned RG7420 medium experiments, measurement of renal endogenous NMN and injection of fluorescence-labeled exogenous NMN. In human renal biopsy with DN, the levels of decreased Sirt1 in PT or Pods and increased Claudin-1 in Pods were correlated

with proteinuria levels. Conclusion: Our results (Hasegawa K, Nature Medicine 2013) suggest that Sirt1 in PTs protects against diabetic albuminuria by maintaining NMN around Pods, thus influencing glomerular function. Although tubulo-glomerular feedback has been previously reported, ours is the first description of a proximal tubular substance (NMN) that communicates with podocytes as a key mediator of intracellular crosstalk. GALLO LINDA A.1, WARD MICHEAL S.1, HARCOURT BROOKE E.1, FOTHERINGHAM AMELIA K.1, MCCARTHY DOMENICA A.1, PENFOLD SALLY A.2, FORBES JOSEPHINE M.1,3 1Glycation and Diabetes, Mater Research Institute-UQ, Australia; 2Diabetes Complications Division, Baker IDI Heart and Diabetes Institute, Australia; 3School of Medicine, Mater Clinical School, University of Queensland, Australia Introduction: The plasma concentration of the reactive carbonyl, methylglyoxal (MGO), is elevated in diabetes. Increased accumulation of MGO may contribute to insulin resistance at peripheral sites of glucose uptake. A deficiency in podocyte insulin signalling impairs podocyte function resulting in kidney disease. Glyoxalase-1 (GLO-1) is an enzyme considered to detoxify MGO. Hence, we examined the effects of inhibiting GLO-1 on podocyte insulin signalling and renal function under diabetic conditions.

In conclusion, we present novel data showing that extensive endoscopic image-guided sinus surgery followed by antibiotic irrigation without additional immunosuppressive treatment decreases IgA and IgG BPI-ANCA levels in patients with CF and also confirm the same effect following lung transplantation. We hypothesize that extensive surgery eradicating infectious foci and a reduction in mucosal inflammation can influence the pathogenic process of autoantibody production, for example BPI-ANCA. Our results are in favour of applying EIGSS in CF patients with intermittent or chronic sinus infections

and also indicate that measuring BPI-ANCA levels in individual patients may be used as a surrogate marker for guiding further therapeutic interventions. We would like to thank Lena Nørregaard, the laboratory RGFP966 price technician at the Department of Clinical Microbiology, Rigshospitalet, the laboratory technicians Enzalutamide concentration at EuroDiagnostica AB and statistician Severin

Olesen Larsen, Statens Serum Institut, for their helpful assistance. The serum analyses performed by EuroDiagnostica AB were financed by Statens Serum Institut. This work was supported by the Candys Foundation, a non-profit organization. Jørgen Wieslander is employed at EuroDiagnostica AB. “
“With increasing interest in alternative options to interferon-alpha-based treatments, IFN-λ has shown therapeutic promise in a variety of diseases. Although

the antiviral activity www.selleck.co.jp/products/cobimetinib-gdc-0973-rg7420.html of IFN-λ has been extensively studied, there is limited knowledge regarding the immunological functions of IFN-λ and how these differ from those of other classes of IFNs. In this study, we investigated the effects of IFN-λ on primary human NK cells, both in a direct and indirect capacity. We demonstrate that in contrast to interferon-alpha, IFN-λ is unable to directly stimulate NK cells, due to the absence of IFN-λ receptor chain 1 (IFN-λR1) on NK cells. However, IFN-λ, in combination with TLR4 challenge, is able to induce the production of select members of the IL-12 family of cytokines in monocyte-derived macrophages. We further show that through macrophage-mediated IL-12 production, IFN-λ is able to indirectly affect NK cells and ultimately induce IFN-γ production. “
“Currently, little information is available regarding innate immunity to helminthic parasite infection. In this study, we isolated the excretory–secretory (ES) proteins from Anisakis simplex (sea mammal intestinal parasite) third stage larva. We determined that the levels of IL-17 in the lung and lung draining lymph node of mice were increased sixfold as a result of intranasal treatment with ES proteins.

Depression is the most common psychological problem among hemodialysis patients and it strongly impacts the patients’ quality of life (QoL). The study aim was to investigate the prevalence of HB in Korean hemodialysis patients and its relationship between health-related QoL and other clinical characteristics. Methods: Clinically stable patients

from 6 hemodialysis centers were enrolled. Thirty-six-item Short-Form Health Survey and temperament and symptom scale of HB, Hospital Anxiety and Depression Scale were used to diagnose and assess health-related QoL and psychological distress, respectively. FK506 molecular weight Sociodemographic factors such as age, sex, education and hemodialysis-related clinical factors (hemodialysis vintage and frequency, Kt/V), and laboratory parameters were assessed. Results: Two hundred and seventy one patients on hemodialysis were enrolled in this study. Fifty-one patients were diagnosed with HB, which was significantly more prevalent than that of general population (18.9% vs. 4.1%, p < 0.01). HB patients were less educated, more depressive and anxious and reported lower level of QoL than the patients without HB. The severities

of HB and depressive symptoms were significantly associated not Venetoclax manufacturer only with mental QoL but also with physical QoL in the final regression models. Anxiety symptom severity and other psychological variables were not associated with QoL in the final regression model. C reactive protein level was negatively associated with both QoL level in this group. Conclusion: After controlling multiple clinical variables, HB, depressive symptoms, and CRP level were significantly associated with mental and physical QoL in hemodialysis patients. Chronic ongoing distress related to hemodialysis may contribute to increased prevalence of HB and depression in hemodialysis patients. More attention to emotional distress of the hemodialysis patients is warranted

to improve their health-related Astemizole QoL. Key words: end stage renal disease; hemodialysis, quality of life; Hwa-byung; depressive symptom HUILGOL SANDEEP, GOPINATH1,2,3,4, VINCENT LLOYD2, AHAMED ISHTHIAQUE3, HEGDE NITHIN4 1Trainee Resident, Dept of Nephrology, Narayana Hrudayalaya Multispecialty Hospital, Bangalore-India; 2Senior Consultant and Head, Dept of Nephrology, Narayana Hrudayalaya Multispecialty Hospital, Bangalore-India; 3Consultant, Dept of Nephrology, Narayana Hrudayalaya Multispecialty Hospital, Bangalore-India; 4Consultant, Dept of Nephrology, Narayana Hrudayalaya Multispecialty Hospital, Bangalore-India Introduction: Despite achieving adequate dialysis, mortality remains high and etiology elusive. Hyperphosphatemia, of chronic kidney disease (CKD) is associated with increased mortality esp. cardiovascular. The purpose of this study is to determine the effect of membrane permeability and phosphate clearance in the low flux versus second generation high flux dialyzers.

UK Renal Association: Guideline 3.5 – CKD: Preparation for dialysis Nephrology Units should provide or facilitate the optimal management of patients with established renal failure who opt for non-dialytic treatment. Kidney Disease Outcomes Quality Initiative: Guideline 1. Initiation of Dialysis CPG for Hemodialysis Adequacy 1.3 Timing of therapy: ‘When patients reach stage 5 CKD (estimated GFR <15 mL/min/1.73 m2), nephrologists should evaluate the benefits, risks, and disadvantages of beginning kidney replacement therapy.

Particular clinical considerations and certain characteristic complications selleck chemical of kidney failure may prompt initiation of therapy before stage 5. (B) Canadian Society of Nephrology: No recommendation.

European Best Practice Guidelines: No recommendation. International Guidelines: No recommendation. 1 Centralized (preferably ANZDATA) collection of actual implementation and completion of ‘Approaching ESKD Checklist/Consent Form’. Gad Kainer has no relevant financial affiliations that would cause a conflict of interest according to the conflict of interest statement set down by CARI. Deirdre Fetherstonhaugh has no relevant financial affiliations that would cause a conflict of interest according to the conflict click here of interest statement set down by CARI. Approaching ESKD: Checklist/Consent Form Interpreter needed □ Yes □ No Language Glycogen branching enzyme required  . . .  . . .  . . .  . . .  . . .  . . .  . . .  . . .  . . .  . . .  . . . Please tick the appropriate box shown in the

‘Action’ Column.   Action Date Comments Clinician’s signature Patient/and or representative signature 1. Discussion between nephrologist and patient (and/or family/legal guardian) re treatment options (including why not an option): • haemodialysis • peritoneal dialysis • transplantation • supportive care only □ Done □ Not done         2. Advice given by nephrologist and documented regarding suggested treatment. □ Done □ Not done         3. Consultation with multidisciplinary team which may include: • pre-dialysis nurse • transplant coordinator • vascular access team • anaemia coordinator • nursing unit manager/s • dietician • social worker • pastoral care • other □ Done □ Not done         4. Invitation to attend education or information session about treatment options and other aspects of ESKD (including advance care planning). Opportunity to meet others in similar circumstances. □ Done □ Not done         5. Attendance at education/information seminar about treatment options and other aspects of ESKD (including advance care planning). □ Done □ Not done         6.

Several genes responsible for epilepsy-associated MCDs have been identified over the past two decades (Table 5),[33, 48] and the functions of these genes have been

intensively studied, mostly in transgenic or knockout mice, allowing for better understanding of the molecular pathomechanisms of each disorder.[48] FCD of Taylor type (T-FCD),[49] a subset of MCDs, has been known to be strongly associated with infantile spasms and medically intractable epilepsy in young children, accounting for 20% of epilepsy patients in some previous reports.[50, Selleck U0126 51] Surgical resection of epileptogenic lesions has evolved as an efficient strategy in the treatment of patients with T-FCD.[52, 53] The lesion is histologically characterized by cortical laminar disorganization and the presence of dysmorphic neurons with/without characteristic large gemistocytic astrocyte-like “balloon cells (BCs)”, and has been classified in some recent proposals as “severe” FCD in the ULCA classification,[54]

FCD type IIA (without BC)/IIB (with BC) in Palmini’s classification[55] or FCD type IIa (without BC)/IIb (with BC) Akt inhibitor in ILAE classification.[56] These histological features are very similar to those seen in cortical tubers of tuberous sclerosis complex (TSC-tubers) (Fig. 6),[48, 57] despite different clinical presentations. Recent evidence has suggested factors significant in the morphogenesis of abnormal cells in dysplastic cortex of TSC-tubers and FCD type IIb, including aberrant expression of cytoskeletal proteins,[58, 59] stem cell markers such as nestin,[60] CD34 class II,[61] neurotrophin receptors,[62] fibroblast growth factor-2[63, 64] and cortical

layer markers,[65] as well as altered mammalian target of rapamycin (mTOR) signaling pathways.[66, 67] Some of these studies, at least from the neuropathological point of view, provided supportive evidence that BCs and dysmorphic neurons represent disturbed gliogenesis Ponatinib molecular weight from matrix cells or radial glia and disturbed maturation of cortical neurons from migrating neuroblasts or intermediate progenitor cells, respectively. These results may also support the “dysmature developmental hypothesis” that epileptogenesis in FCD type II is the consequence of local interactions of dysmature cells having immature cellular and synaptic properties with normal post-natal neurons.[68] The presence of dysplastic oligodendroglial cells has also been suggested in MCDs with BC (TSC-tubers and FCD type IIb).

, 2006). However, the transcription of icaR in the S. epidermidis Spx-overexpressing strain was at a level similar to WT, indicating that Spx does not affect the transcription

of icaADBC by modulating icaR. Spx might directly repress the transcription of icaADBC or indirectly by downregulating a positive regulator of the icaADBC operon, such as SarA (Tormo et al., 2005), SarZ (Wang et al., 2008) or other unidentified factors. In our previous work, an S. epidermidis clpP mutant strain displayed decreased primary attachment, PIA production and biofilm formation (Wang et al., 2007). This may have been due to the accumulation of Spx in the clpP mutant strain, as Spx has negative effects on primary attachment, PIA production and biofilm formation of S. epidermidis. Interestingly, the transcription of icaADBC was negatively affected by the overexpression Autophagy inhibitor solubility dmso of Spx in the clpP mutant strain (Wang et al., 2007). This implies the existence of another substrate of ClpP protease that either interferes with the regulation of icaADBC by Spx or has a positive effect on the transcription of icaADBC that counteract the effect of Spx. An attempt to construct Selleckchem Opaganib an S. epidermidis spx mutant strain was unsuccessful, suggesting that the spx gene might be essential in S. epidermidis. It is noteworthy that a previous attempt to delete the spx gene (denoted as yjbD) in

Listeria monocytogenes also failed (Borezee et al., 2000), and in S. aureus, the spx mutant strain was only successfully constructed in strain 8325-4 (a σB-deficient strain with a small deletion in rsbU) with a low frequency and reduced size under normal

growth conditions (Pamp et al., 2006). Although the author showed that the transcription of spx was at a similar level between a σB-positive WT (SH1000) and the strain 8325-4, this does not guarantee that the phenotypes modulated by Spx would be the same in these two strains. It has been demonstrated that σB affects a wide range of phenotypes in strain 8325-4 Enzalutamide order (Horsburgh et al., 2002). Whether the defect of σB has interfered with the spx knockout is unknown. Besides, the observation that all 80 tested clinical isolates of S. epidermidis in our study harbor the spx gene also supports this view. The observation that overexpression of Spx has no effect on the stress response indicates that either Spx may not be involved in the general stress response or the concentration of Spx in WT has already exceeded the threshold for bacterial cells to adapt to the selected stress conditions. In conclusion, we found that Spx has negative effects on primary attachment, PIA production and biofilm formation and is a substrate of ClpP protease in S. epidermidis. Our results suggest that ClpP may positively contribute to the biofilm formation of S. epidermidis by degrading Spx, a negative regulator of biofilm formation. The mechanism of Spx modulating the biofilm formation of S. epidermidis will be further investigated. We thank Prof.