These studies provide evidence that the strength of the TCR signal can play a direct role in directing the extent of

both thymocyte deletion and Treg-cell differentiation, and suggest that distinct TCR signaling thresholds and/or pathways can promote CD4SP thymocyte deletion versus Treg-cell formation. “
“In June this year, it was 30 years since the identification of the first AIDS patient (see the review in this issue 1). Despite rapid responses PCI-32765 solubility dmso by scientists and doctors to understand this disease in both clinical and experimental systems 2, 3, human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS (Fig. 1), continues to feature among world’s three major killers destroying millions of lives, families and communities. More than 30 drugs have been developed just for HIV-1 and there have been three successful trials showing their impressive preventive potential. However, because of the drug unavailability, particularly in resource selleck compound poor settings, side effects and potential development of resistance, the best hope for a profound fall in the incidence of HIV-1 infection remains the development of an effective prophylactic HIV-1 vaccine. Here, we discuss

T-cell vaccine designs mainly, briefly mentioning antibody vaccines. Even if a vaccine that actively stimulates broadly neutralizing antibodies (bNAbs) can be made 4, it will be hard to stop some HIV-1 infection occurring (e.g. through cell–cell transmission) and T-cell-mediated

immune responses to control infection will be required. T cells function by killing HIV-1-infected cells and producing soluble factors that can directly and indirectly control HIV-1 spread. While T cells cannot prevent the transmitted virus from infecting host cells, potent vaccine-induced HIV-1-specific T-cell responses could increase the dose of incoming virus necessary to establish infection (i.e. decrease acquisition) IMP dehydrogenase 5, limit the extent of viral replication during primary viremia (i.e. reduce tissue damage), lower the virus load at set point (i.e. reduce further virus transmission) and slow the rate of CD4+ T-cell decline (i.e. delay the development of AIDS). The simian immunodeficiency virus/macaque challenge model strongly supports this view, showing that potent T-cell responses alone can lower virus load and delay the development of AIDS 6–8. Thus, ideally, a successful HIV-1 vaccine will induce both T-cell and antibody responses; however, an effective T- or B-cell vaccine alone is nonetheless likely to impact the epidemic 9. Scientists developing HIV-1 vaccines face a long list of challenges. Although these differ for the induction of effective T-cell responses in comparison with induction of the desired bNAb specificity by active immunization, one major hurdle is common, namely the extreme HIV-1 variability.

It may appear complex and driven by technical

language. At its heart, however, it asks a simple question: in the circumstance of this patient what is the right thing to do? An approach based on the key ethical principles provides a structure in the decision-making process around the appropriateness of dialysis; in this way ethics can lead to better and more nuanced decision-making. Several guidelines on the initiation of and withdrawal from dialysis provide assistance in these deliberations, including the (USA) RPA guidelines and to a lesser extent the CARI guidelines. Each of the bioethical principles is important. Autonomy does not override the other principles. All clinicians, including Nephrologists, have a responsibility to carefully balance the benefits and burdens

of treatment, including dialysis, and communicate that recommendation to the patient and family. The wishes and values of a patient should NVP-LDE225 mw be considered but they should not, taken alone, be determinative. This issue arises when a patient or family wants treatment that is not felt Roxadustat molecular weight to be appropriate by the nephrologist. In difficult cases Nephrologists should seek the advice and formal opinion of colleagues and, where available, a Bioethicist. This is particularly useful when conflict arises within families about which treatment pathway should be adopted. Advance care planning is a process of patient-centred discussion, ideally involving family/significant others, to assist the patient to understand how their illness might affect them, identify their goals and establish how medical treatment might help them to achieve these. An individual must be competent to make decisions about their healthcare in order to participate in Advance Care Planning. Advance Care Planning discussions may result in the formulation ZD1839 nmr of an Advance Care Plan which articulates the individual’s wishes, preferences, values and goals relevant to their current and future health care.

An Advance Care Plan is only one useful outcome from the Advance Care Planning process, the education of patient and family around prognosis and treatment options is likely to be beneficial whether or not a plan is written or the individual loses decision-making capacity at the end of life. Advance care planning should be available to all patients with CKD, including ESKD on renal replacement therapy. Such plans need to be reviewed regularly as patients’ circumstances may change. Advance care planning provides benefits to patients as their end of life wishes are more likely to be known and followed when individuals have been through the Advance Care Planning process; feelings of isolation and lack of hope may be experienced when individuals are not able to honestly and openly discuss their hopes and fears for the future with loved ones. Having Advance care discussions does not result in loss of hope for patients.

0104 is needed to induce significant PAR-4 expression. As it is unlikely to accumulate such a high concentration of the allergens in the body, upregulated PAR-1 and PAR-4 expression should not play an important role in cockroach allergy. In contrast, Per a 1.0101-induced upregulation of expression of PAR-2 may be involved in cockroach allergy as only 100 ng/ml

of Per a 1.0101 is required to induce significant increase in PAR-2 expression. Activation of PAR-2 has been recognized to play an important role in allergic diseases. Patients with asthma express an increased amount of PAR-2 on respiratory epithelial cells [20], and PAR-2 activation in human airways is associated with contraction selleck chemicals llc learn more of human airways and contributes to the hyperplasia and hyper-responsiveness evident in the asthmatic airway [21]. Furthermore, our results indicate that Per a 1.0101 and Per a 1.0104 are not proteases. Therefore, their actions on PARs should not depend on enzymatic activity. Once again like rPer a 7, we observed the expression of certain mRNAs of PARs, but not corresponding proteins in P815 cells upon rPer a 1.0101 and rPer a 1.0104 challenge. This dissociation

between gene and protein expression has been reported previously [22] and there are many complicated and varied post-transcriptional mechanisms involved in turning mRNA into protein [23], which may help to explain our earlier observations. Like Per a 7, both rPer a 1.0101 and rPer a 1.0104 can induce secretion of Th2 cytokines IL-4 and IL-13 from P815 cells. As overexpression of IL-4 is predominantly found in the airways of asthmatics [24] and IL-4 is the key cytokine in development of Th2 cell responses [25], IL-13, which shares a receptor component with IL-4, is a critical cytokine for allergen-induced asthma [26], and the findings that rPer a 1.0101 and rPer a 1.0104 can induce IL-4

and during IL-13 release from mast cells may be of importance for cockroach allergy. As much lower concentrations of rPer a 1.0101 and rPer a1.0104 are required to induce IL-4 and IL-13 release than to upregulate expression of PARs, cytokine release may be an earlier event than altered expression of PAR expression when mast cells are challenged by Per a 1.01 allergens. In conclusion, we have demonstrated for the first time that American cockroach allergens Per a 1.0101 and Per a1.0104 have no enzymatic activity, but can modulate the expression of PARs in P815 cells. They can also provoke Th2 cytokines IL-4 and IL-13 secretion from the mast cells. Our results suggest that Per a 1.0101 and Per a1.0104 are likely to contribute to the development of cockroach-related allergic disease through modulation of mast cell behaviour. This project was sponsored by the grants from the Li Ka Shing Foundation, Hong Kong, China (No. C0200001); the Major State Basic Research Program of China (973 Program) (No.

The same group also identified a homologue of the C. elegans multi-membrane spanning, RNA importing protein SID-1. The gene encoding this protein contains 21 exons and spans over 50 kb to potentially https://www.selleckchem.com/products/pci-32765.html encode a 115 556 Mr protein (SmSID-1) (38). These findings indicate that an intact RNAi

pathway has evolved in schistosomes. It has now also been shown that RNAi can be experimentally applied in schistosomes and appropriate transformation protocols have been adapted and developed (Table 2). The first report of successful RNAi in schistosomes was published in 2003 (40) showing that soaking of S. mansoni cercariae in dsRNA resulted in silencing of the major gut-associated proteinase, cathepsin B (SmCB1 or Sm31). In the same year, Boyle and colleagues (41) reported the successful silencing of the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and of a glucose transporter (SGTP1) gene in sporocysts of S. mansoni. Here for the first time a functional phenotype was detectable as the exposure of the parasite to SGTP1

dsRNA reduced the ability of sporocysts to take up glucose by 40%. These two publications R428 concentration clearly confirmed that RNAi can be utilized in schistosomes and that the silencing effect in larval stages of the parasite was potent and specific. In short succession, RNAi studies in schistosomes were published by a number of groups. The proteins attracting the most interest were proteolytic enzymes (metallo-, cysteine, and serine proteases), genes belonging to signalling pathways implicated in adult worm pairing and/or egg deposition, or genes playing a role in reproduction. These groups of proteins are essential in the life cycle of schistosomes and therefore are potential targets for

novel anti-parasite chemotherapy and immunotherapy. A number of studies have been undertaken to understand the role of signal transduction pathways in schistosomes and their role in the interaction of the parasite with its host environment and amongst themselves. One such example is the TGF-β signalling pathway that seems to be essential for schistosome embryogenesis. Schistosomes are exceptional amongst trematodes in the way that they have evolved separate sexes, and Cell press the sexual development of the female requires constant contact with the male. Blocking components of the parasite TGF-β signalling pathway by RNAi would likely abolish worm pairing and egg production, and as a consequence, egg-associated pathology will not develop. This makes this pathway a potential target for novel intervention strategies for transmission and disease control (42–45). Indeed, Freitas et al. (42) described that RNAi-mediated knock-down of SmInAct (a member of the TGF-beta superfamily) expression in eggs led to a developmental arrest indicating a role of this protein during embryogenesis of schistosomes. Another signal transduction pathway was investigated by Beckmann et al. (46). The authors silenced a Syk kinase, which is expressed in the gonads of adult schistosomes.

In contrast to mice, CD25 deficiency in humans is accompanied by severe immunodeficiency that is characterized by susceptibility to opportunistic pathogens and a normal Treg frequency [9, 14, 15, 21-24]. In addition, IL-2-deficient mice are fully capable of rejecting allografts, whereas CD25-deficient humans are not [24, 49, 50]. Therefore, CD25 may be more important for effector function in humans and more

important for tolerance in mice since only Treg cells constitutively express CD25 in mice. This may explain why blocking CD25 during tumor immuno-therapy has not translated well from mice to humans [51]. Discrepancies between mouse and human immunology Selleckchem Autophagy inhibitor have been described elsewhere and is not unexpected since the species diverged 65–75 million years ago [52]. Therefore, studies conducted in mice on the role of IL-2 Selleck Palbociclib in T-cell function may not exactly translate to humans, and this study may offer one possible explanation for these differences.

We believe that the discovery of this CD4+CD25INT population is particularly important for therapies that target CD25/IL-2 and that hopefully by studying the response of this population we can better understand the mechanism of these therapies and improve their clinical efficacy. We evaluated the response of the CD4+CD25INTFOXP3− population to IL-2 immunotherapy. Over the course of IL-2 immunotherapy in cancer patients, the percentage

of CD4+ T cells that were CD25INT population decreased, while the CD25NEG increased and Treg populations stayed relatively stable, L-NAME HCl suggesting these populations were differentially affected by the therapy. From these studies, it was clear that the CD25INT population was affected by the IL-2 therapy, however, it is currently not known exactly how the CD25INT population responded to the therapy. One possibility is that the CD25INT cells may have downregulated or shed CD25 [53]. However, we did not see diminution of CD25 on the Treg cells, and we demonstrated that not all of the CD25INT population downregulated expression of CD25 in response to rhIL-2 in vitro and that some even increased CD25 expression. In addition, in vitro stimulation with rhIL-2 also suggested that the CD25INT cells are differentially responsive to rhIL-2, as shown by Ki67 staining, and could therefore be act-ivated to a greater degree than the CD25NEG and Treg populations. Therefore, we believe that the disappearance of the CD25INT population observed in IL-2 cancer patients is most likely a combination of events, including decreased surface expression of CD25 and increased activation, which might have led to AICD and/or egress from the blood to tissue. Nevertheless, it is clear that the CD25INT population is greatly affected by IL-2 immunotherapy and may be integral to the antitumor immune response.

c.) infected with L. amazonensis or L. braziliensis stationary promastigotes (2 × 106 in PBS) in the right hind foot. At indicated time of infection, we collected popliteal draining LN cells and splenocytes from individual compound screening assay mice. To ensure sufficient cells for staining and subsequent analyses, we conveniently pooled draining LN cells within the group into two sample sets, such as three draining LNs into one set and the other two draining LNs into the other set. Cells were then stimulated with a PMA/ionomycin/Golgi Plug (BD Biosciences) for 6 h. Cells were first stained for surface markers, including CD3, CD4 and individual TCR Vβ. Then,

the intracellular IFN-γ production was stained following cytofixation/permeabilization with a Cytofix/Cytoperm Kit (BD Biosciences). The percentages of CD4+ TCR Vβ+ cells gated on CD3+ cells and TCR Vβ+ IFN-γ+ cells gated on CD4+ cells were analysed on the FACScan (BD Biosciences), and results were analysed using FlowJo software (TreeStar, Ashland, OR, USA). To obtain the absolute cell number of CD4+Vβ+ cells, we first got an averaged cell number per draining LN from each sample set. We then calculated the absolute cell number of CD3+ CD4+ TCR Vβ+ cells by multiplying the averaged absolute cell number per LN by their corresponding percentages of positively stained cells (CD3, CD4 and the individual

TCR Vβ in CD4 cells). For TCR Vβ analysis of lesion-derived cells, foot lesional tissues were collected and pooled as mentioned earlier and digested in the complete Iscove’s modified Dulbecco’s medium containing 10% FBS, 1 mm sodium pyruvate, 50 μm BGB324 molecular weight 2-ME, 50 μg/mL gentamicin and 100 U/mL penicillin, as well as collagenase/dispase (100 μg/mL) and DNase I (100 U/mL; Roche), for 2 h at 37°C. After passage through the cell strainer (40 μm; BD Biosciences), the single-cell suspension was on the top of 40% and 70% Percoll solution (Sigma). After centrifugation for 25 min at room temperature,

the purified Cepharanthine cells from a 40/70% layer of Percoll were collected and stained with CD3, CD4 and TCR Vβ Abs. The percentages of TCR Vβ+ cells gated on CD3+ CD4+ cells were analysed by FACS. B6 mice were infected with 2 × 106La or Lb promastigotes for 4 weeks. Draining LN cells were restimulated with the corresponding La or Lb antigens for 3 day, and CD4+ T cells were purified via positive selection. Naïve CD4+ T cells were used as controls. TCR Vβ repertoire clonality for purified CD4+ T cells was analysed by RT-PCR and gel-based assays using specially designed SuperTCRExpress™ kits by scientists in BioMed Immunotech Incorporation (Tampa, FL, USA). Leishmania braziliensis stationary promastigotes (2 × 106) were injected subcutaneously (s.c.) in the right hind foot. After the healing of lesions at 8 or 24 weeks, some of the mice were injected with stationary promastigotes of La (2 × 106) in the left hind foot. Naïve mice were similarly infected and used as controls.

1d). Concentration of lidocaine, bupivacaine and ropivacaine has a significant effect on cell death (for lidocaine P < 0·001, bupivacaine P < 0·001 and ropivacaine P = 0·001). Group arrangement also influences cell survival significantly: P = 0·001 for lidocaine, P = 0·029 for bupivacaine and P = 0·01 for ropivacaine.

Cell viability determined in fibroblasts from group 1 showed a similar pattern to trypan blue assays: only minor impairment over time was observed for the three buy LDE225 LA with the 0·3 mg/ml concentration (Fig. 2a). While viability was not diminished after incubation with lidocaine and ropivacaine at a 0·6 mg/ml concentration, MTT decreased time-dependently after incubation with bupivacaine (Fig. 2b). In group 2, MTT did not change upon incubation with lidocaine and ropivacaine with the lower concentration. However, no cells survived after 9 days of bupivacaine exposure (Fig. 2c). With the higher concentration, fibroblasts experienced serious impairment of viability with increasing exposure time. The most pronounced effect was observed in the bupivacaine group (Fig. 2d). Correlation analysis revealed a time- and concentration-dependent effect on cell viability for all three LA with the following values: lidocaine time P = 0·019, concentration P < 0·001; bupivacaine time P = 0·05, concentration P < 0·001; ropivacaine time P = 0·004, concentration P < 0·001. An effect based on the type

of stimulation (group 1 or 2) was not observed. Thymidine incorporation over time upon incubation AT9283 cost with each of the three LA was not changed after exposure to a low concentration of LA (Fig. 3a). With the 0·6 mg/ml concentration, again the proliferation rate was decreased only in the bupivacaine Protein kinase N1 group (Fig. 3b). In group 2, with continued incubation with the low LA concentration, the proliferation rate decreased to 80% in the lidocaine and ropivacaine groups (Fig. 3c). This effect

was more pronounced with the 0·6 mg/l concentration. Bupivacaine had a more pronounced effect on thymidine incorporation with both concentrations compared to the two other LA (Fig. 3d). LA concentration had a statistically significant impact on proliferation rate (lidocaine: P < 0·001, bupivacaine: P < 0·001, ropivacaine P = 0·001), as did the group constellation (lidocaine: P < 0·001, bupivacaine: P = 0·009, ropivacaine P = 0·001). Fibroblast apoptosis was determined upon exposure to lidocaine, bupivacaine and ropivacaine. In group 1, apoptosis rate was diminished for all three LA in a similar manner for both concentrations (Fig. 4a and b). With permanent incubation with LA, the apoptosis rate decreased in a time- and concentration-dependent fashion for lidocaine. An increase in the apoptosis rate was observed at 3 days of incubation with the 0·3 mg/ml (bupivacaine, ropivacaine) and 0·6 mg/ml (ropivacaine) concentrations (Fig. 4c and d).

5B). These results were in line with immunohistochemical data showing Palbociclib molecular weight that a higher percentage of CD4+ lymphocytes than neutrophils were positive for IL-17 (Fig. 4). Importantly, the IL-17 we detected on cells

could have originated from endogenous or exogenous factors and bound by IL-17 receptors on cell surfaces [21, 22]. To determine if these leukocytes were actively expressing IL-17, the cells were subjected to fixation and permeabilization. The fluorescence intensity of IL-17 staining increased slightly, but with statistical significance, in both CD4+ T cells and Ly-6G+ cells (Fig. 5B and Supporting Information Fig. 5). These resulted indicated that infiltrated lymphocytes and neutrophils express IL-17. Since fungal growth and leukocyte infiltration coordinately contribute to corneal destruction, Volasertib we wondered whether either of these processes was occurring in inoculated nude mice. In inoculate BALB/c mice, pseudohyphae were detected as early

as 6 h postinoculation and abundant by 12 and 24 h postinoculation (Fig. 6A). In striking contrast, few pseudohyphae were detected at these time points in nude mice. Similarly, leukocyte infiltration was already obvious in the corneas of BALB/c mice at 6 h, but few leukocytes were present in nude mice throughout the observation period (Fig. 6A and B). Colony-forming assay showed that the pathogen burdens gradually increased in immunocompetent mice, but decreased in nude mice soon after inoculation (Fig. 6C). Together, these results suggest that nude mice have an innate mechanism that inhibits Candida blastospore transformation

and leukocyte infiltration. In Rutecarpine support of the latter, real-time polymerase chain reaction (RT-PCR) assay demonstrated that the expression of chemokines (e.g. CXCL12, CXCL10, CXCL2, CXCL1, and CCL2) including the IL-17 inducer IL-6 was upregulated during the first day of inoculation in BALB/c and nude mice, but their levels were significantly lower in nude mice (Fig. 6D). To determine whether the decreased production of chemokines in nude mice corneas was an intrinsic property of resident corneal cells rather than systemic immune components, cornea buttons were removed following inoculation and placed in overnight culture in vitro. Like the findings above, corneal buttons of nude mice showed decreased chemokine production compared with those of BALB/c mice (Fig. 6E). Corresponding to the fact that IL-17-neutralized mice became insensitive to CaK induction, the inoculated corneas of anti-IL-17-treated mice had reduced production of above chemokines compared with isotype control antibody-treated mice (Supporting Information Fig. 6). Our results indicated that reduced chemokine production is correlated with CaK resistance in nude mice.

Chronic kidney disease (CKD) is a global public health problem involving increased risk of cardiovascular disease (CVD) and premature death. Psychosocial explanations of health involving social, psychological and physiological processes all interact to affect the aetiology and development of CKD.[1] For example, social processes such as social support may lead to psychological changes at the individual level which may influence health directly via physiological processes or modified behaviours.[2] Psychosocial factors are important both because they have an

impact on quality of life and have been shown to influence the progression of various chronic diseases.[3, 4] However, our understanding of the burden and impact of these potentially modifiable risk factors in CKD is limited. Rates of CKD are increasing in Australia Inhibitor Library Neratinib research buy with the number of patients commencing renal replacement therapy (RRT; dialysis or transplantation) between 1990 and 2009 escalating by 321%.[5] In addition to those being treated, around 36% of people with advanced CKD are not being dialysed[6] and a similar proportion are dying via withdrawal from dialysis.[7] In light of this increasing social and economic burden, examining the role of potentially modifiable non-biological risk factors on the disease trajectory of CKD should

be a priority. This paper examines the prognostic role of several key psychosocial factors (depression, anxiety and perceived social support) and health-related quality of life (HRQOL) in adults with CKD (i.e. CKD stage 1–5, unless otherwise stated) prior to RRT. We explore current gaps in the literature and examine potential mechanisms through which these factors may affect health outcomes. Potential interventions and suggestions for future research are also outlined. Depression is a chronic and recurrent illness associated with substantial morbidity Pregnenolone and all-cause mortality. Comorbid depressive disorders in patients with chronic disease reduce quality of life, and increase functional disability and use of healthcare services.[8] Unemployment,

low income, low perceived social support, and changes in familial and occupational roles are recognized risk factors for depression in people with CKD.[9-12] While identifying depression in patients with kidney disease is complicated by the potential misclassification of uraemic symptoms as somatic symptoms of depression, prevalence estimates for clinical depression in dialysis patients (CKD 5D) range from 20% to 30%.[13, 14] Similarly, around 22% of individuals with pre-dialysis CKD fulfil the criteria for major depression[15, 16] while 37–55% report depressive symptoms.[16-18] This is higher than the prevalence of depressive disorders in the general population (7%)[9] and in those with other chronic diseases including cancer (11%).

tropicalis (21%), C. parapsilosis (21%) and C. glabrata (5%). A similar study conducted by Chang et al. [11] in Mato Grosso do Sul, Brazil, detected the presence of C. albicans (45.8%), C. parapsilosis (34.4%), C. tropicalis (14.6%) and C. glabrata (5.2%) in venous blood samples from hospitalised patients. selleck A current study conducted by Motta et al. [12] in the largest Brazilian teaching hospital complex demonstrated a similar profile, with C. albicans showing the highest incidence (52.2%), followed by C. parapsilosis (22.1%), C. tropicalis (14.8%) and C. glabrata (6.6%). The incidence of infections due to non-albicans Candida spp. is increasing[4] although

C. albicans remains the species of greatest clinical interest.[13] Currently,

there are about 17 species known to cause invasive or superficial mycoses. Based on a recent study, non-albicans Candida spp. are responsible for 35% to 65% of all candidiasis cases.[14] According to Glolo and Svidzinski [15], the most common species involved in the infectious processes are C. tropicalis, C. parapsilosis, C. krusei, C. kefyr, C. norvegensis, C. rugosa, C. guilliermondii, C. lusitaniae, C. ciferrii, C. haemulonii, C. lypolytica, C. pulcherrima, C. catenulata, C. utilis, C. viswanathii Everolimus chemical structure and C. seylanoides. Many factors may predispose an individual to infection, among them the use of broad-spectrum antibiotics, being a transplant patient, prolonged hospitalization and invasive surgical procedures such as the use of vesical catheters, venous catheters and mechanical ventilation.[15, 16] Other ROS1 factors, such as extreme age, immunosuppression, renal failure, diabetes, chemotherapy,

radiotherapy, mucosal injury, haemodialysis, previous surgery, corticotherapy and use of dental prostheses, can also play a role.[17-19] The ability of Candida to cause infection also depends on its intrinsic virulence attributes.[20] Yeast of the genus Candida spp. possess several virulence-associated factors that ensure their ability to colonise and cause infection. These include the ability to adhere to host cells, promoting phenotypic changes, converging between yeast and pseudohyphae forms, the ability to form biofilms, producing substances harmful to cells, such as haemolysins, the ability to resist hydrogen peroxide and derivatives and the ability to produce and secrete hydrolytic enzymes. These factors can facilitate the promotion of infections in susceptible hosts and ensure microbial permanence to colonise or invade host tissues.[20-22] Candida albicans has well-known pathogenic potential, due to its ability to adhere to mucosal and epithelial cells, phenotypic transition with the production of hyphae that help tissue invasion, significant thermotolerance and the production of hydrolytic enzymes.[23, 24] In addition, C. albicans forms biofilms that adhere to and colonise surfaces.