2 Properly conducted randomization balances the distribution of both known and unknown factors that may influence outcomes equally between the trial arms. This means that the only remaining difference among participants in the trial arms should be the intervention. However, it should be noted that because of chance, successful randomization does not necessarily guarantee a complete balance in participant characteristics

or risk factors.3 As such, adjusted methods of randomization can be employed to help achieve this balance. Such methods Rapamycin order include permuted block randomization and stratified block

randomization that are particularly ideal for ‘small’ studies. When reading a trial report, it is critical to assess the randomization process used and determine whether it was successful or not (Table 1). The article you identified from your literature search provides a clear description of the randomization process in the methods section. Randomization was performed learn more in blocks assuring a 1:1 ratio between treatment groups within strata defined by a range of parameters. In addition, a table outlining the baseline characteristics of the study population according to treatment allocation is provided.1 It tells you that a total of 2103 patients were randomized into one of two groups, the active treatment

group received sevelamer (n = 1053) and the control group received calcium-based phosphate binders (n = 1050) and that there are no important differences in baseline characteristics that could affect how participants respond to treatment between these two groups. It therefore appears that successful randomization was achieved. If there had been differences in the baseline characteristics of the treatment groups, the potential PAK5 effect of these differences would have had to be considered when interpreting the results, and the randomization methods carefully scrutinized. For example, in the appropriate blood pressure control in diabetes trial, differences in baseline characteristics across treatment groups were present, and the trial results were discrepant from other trials evaluating similar interventions.4 Question: Was randomization adequately concealed? As the term suggests, allocation concealment is used to mask the treatment allocation of participants from investigators and participants before their participation in the study.

Thereafter the posterior thighs selleck were dissected from medial to lateral, distinguishing the perforators at the level of the superficial fascia. The perforators were localized and origin, source, length and diameter of the perforators were documented. Analysis occurred using ANOVA and the two proportion Z test. The distribution of musculocutaneous and septocutaneous perforators was respectively 69.1% and 30.9% (P = 0.002). The PTR was divided in thirds. Most perforators (53.2%) were found in de middle third of the PTR. The deep femoral artery (DFA) was the main origin of perforators (61.7%), followed by the superficial femoral artery (SFA) (27.7%) and the popliteal

artery (PA) (10.6%). The DFA Selleckchem PS341 perforators were the longest with a mean length of 13.7 ± 4,69 cm, the SFA perforators were 9.79 ± 3.76 cm and the PA perforators were 8.6 ± 3.37 cm. The PTR offers a sufficient number of suitable perforators to serve as an adequate donorsite for pedicled and free flaps. © 2013 Wiley Periodicals, Inc. Microsurgery 33:376–382, 2013. “
“Defects of the Achilles tendon and the overlying soft tissue are challenging to reconstruct. The lateral-arm flap has our preference in this region as it provides thin pliable skin, in addition, the fascia and tendon can be included in the flap

as well. The aim of this report is to share the experience the authors gained with this type of reconstruction. The authors report the largest series in the published reports today. Patients and methods: A retrospective review was performed of all patients treated between January 2000 and January 2009 with a lateral-arm flap for a soft-tissue defect overlying the Achilles tendon. Results: In the reviewed period, 16 soft-tissue defects overlying the Achilles tendon were reconstructed, with a mean follow-up of 63 months. In three cases, tendon was included into the flap and in two, a sensory nerve was coapted. Fifteen cases (94%) were successful, one failed. In seven cases, a secondary procedure PRKD3 was necessary for thinning of the flap. Conclusion: The lateral-arm flap

is a good and safe option for the reconstruction of defects overlying the Achilles tendon. © 2012 Wiley Periodicals, Inc. Microsurgery, 2012. “
“Severe injuries at foot and ankle level with loss of soft tissues and bone are often treated by means of amputation. The transfer of composite free flaps from various donor sites may provide anatomical reconstruction of the foot and ankle and function. Ten patients who sustained severe combined tissue injuries of the foot requiring reconstruction with composite free flaps were studied with a mean follow-up of 3.4 years. A thorough clinical examination was performed, and gait analysis was carried out with kinetic and kinematic parameters. Bone integration and healing was observed with satisfactory foot morphology.

38 and 2.45, respectively]. Using multiple SNPs in the logistic regression for covariates, wild-type AhR and mutant AhRR combination was significantly higher in patients (67.8%) than in controls (48.0%) (OR = 2.76). On the other hand, mutant AhRR in combination with GSTM1 null genotype was significantly higher in patients

(35.5%) than in controls (19.3%) (OR = 6.12). Conclusion  Polymorphisms of dioxin receptor complex components and detoxification-related genes jointly confer susceptibility to advanced-stage endometriosis in the Taiwanese Han population. “
“Clostridium difficile is a pathogen responsible for diarrhoea and colitis, particularly after antibiotic treatment. see more We evaluated the C. difficile protease Cwp84, found to be associated with the S-layer proteins, as a vaccine antigen to limit the C. difficile intestinal colonization and therefore the development of the infection in a clindamycin-treated hamster model. First, we evaluated the immune response and the animal protection against death induced by several immunization routes: rectal, intragastric and subcutaneous. Antibody production was variable according to the immunization routes. In addition, serum Cwp84 antibody titres did not always correlate with animal protection after challenge with a toxigenic 5-Fluoracil order C. difficile strain. The best survival rate was observed with the rectal route of immunization. Then, in a second assay, we selected

this immunization route to perform a larger immunization assay including a Cwp84 immunized group and a control group. Clostridium difficile intestinal colonization and survival rate, as well as the immune response were examined. Clostridium difficile hamster challenge resulted in a 26% weaker and slower C. difficile intestinal

colonization in the immunized group. Furthermore, hamster survival in the Cwp84 immunized group was 33% greater than that of the control group, with a significant statistical difference. Following the disruption of the normal bowel microbiota by antibiotic therapy, Clostridium difficile colonizes the gut, resulting in a spectrum of diseases ranging Thiamet G from asymptomatic carriage to pseudomembranous colitis (PMC) (Kelly & LaMont, 1998; Wilcox, 2003). The disease symptoms are mediated by two secreted enterotoxins: TcdA and TcdB. Clostridium difficile is shed in the faeces as spores that persist in the environment and facilitate the colonization of new individuals. Clostridium difficile is thus a particular problem in health care facilities, where transmission easily occurs between patients and from carriers to patients (McFarland et al., 1989). Measures to prevent C. difficile infection (CDI) through patient isolation are costly and have had variable success. Although previously considered rare, the incidences of community-acquired CDI and colitis are on the increase. After the acquisition of C.

Supernatants were harvested and counted on an automated gamma counter. Percent specific lysis was calculated as [(sample 51Cr releasespontaneous

51Cr release)/(maximum 51Cr releasespontaneous 51Cr release)]×100. In vivo cytotoxicity experiments were performed as described with modifications 35. Naïve splenocytes (target cells) were pulsed with 1, 0.1 or 0.01 μg/mL of JEV NS4b S9, WNV NS4b S9 peptide or control influenza NP 366–374 peptide (1 μg/mL) for 45 min at 37°C. Cells were stained with 1 μM Cell Trace Far Red 7-hydroxy-9H- (1,3-dichloro-9,9-dimethylacridin-2-one)-SE (DDAO-SE; Invitrogen, Carlsbad, CA, USA) and serial dilutions of CFSE (5 μM, 1.5 μM, 0.4 μM, 0.1 μM; Invitrogen). Target selleckchem cells in PBS (2×107 cell/mL) were injected i.v. into JEV-immunized or naïve mice 8 days post immunization. Splenocytes were harvested 2 h later

and analyzed using a FACSAria. Percent specific lysis was calculated by the formula 1(Ratio immune/Ratio naïve)×100, where Ratio=(♯ events of JEV or WNV peptide/♯ events of control influenza peptide). Recombinant H-2Db:Ig fusion protein (4 μg; BD Biosciences) was loaded with variant peptides (>90% purity) at 640 molar excess peptide in PBS (pH=7.2) at 37°C overnight according to manufacturers guidelines. Peptide-loaded dimer was incubated with 2.4 μg APC-anti-mouse IgG (BD Biosciences, mAb A85-1) followed by incubation with purified mouse IgG isotype control (4 μg; BD Biosciences; mAb A111-3). Splenocytes were resuspended in PBS, stained with Live/Dead Aqua and incubated with anti-CD16/32 (2.4G2; BD Bioscience), followed by staining with 4 μg of peptide-loaded dimer. Cells Torin 1 were surface stained with anti-CD44, anti-CD62L, anti-KLRG1 and anti-CD127 conjugated with FITC, PE-Cy7 and PerCP-Cy5.5, washed and resuspended in BD stabilizing buffer. Peptide-loaded dimer staining levels in naïve mice were subtracted from experimental Carbohydrate values in infected mice. The gating strategy is shown in Supporting Information Fig. 3A and B. On days 3 and 7 post JEV or WNV infection, spleen, brain and serum were obtained

and flash frozen at −70°C. Tissues were homogenized to give a 10% (spleen) or 20% (brain) homogenate based on tissue weight using a Qiagen mixer mill. Serial dilutions were made in MEM and titers were determined on Vero cells as described 36. Plates were incubated for 2 (WNV) or 4 days (JEV Beijing and SA14-14-2) prior to second agar overlay. The limit of detection was 50 pfu/mL for serum, 250 pfu/g for brain and 500 pfu/g for spleen. Means, medians and standard errors were calculated using GraphPad Prism (GraphPad Software, LaJolla, CA, USA). Comparisons of variables between JEV and WNV infection groups were performed with log transformed data using the Mann–Whitney U test on STATA software (StataCorp, College Station, TX, USA). p<0.05 was considered significant. This work was supported by contract N01-AI25490 and grants U19 AI057319, P30 DK032520 and T32 AI007349 (D.W.

Cultures were collected from the different anatomical sites of all the patients within 24 h of diagnosis of candidemia. Molecular similarities between identical species colonised with Candida species were evaluated via karyotyping. The colonisation index, as developed by Pittet et al. was calculated using screening culture results from patients. Among the 40 patients screened for colonisation, 35 (87.5%) had colonisation of at least one anatomical site. Twenty-six (74.3%) of the 35 patients with colonisation in any of the three anatomical sites (respiratory, rectum and urinary sites) were shown to be colonised with the same species that caused candidemia. When the anatomical sites

were compared with each other, no significant difference was observed at the species level in terms of colonisation index. The colonisation index (≥0.5) positivity rate was 74% in patients with candidemia. PI3K inhibitor selleck screening library The investigation of Candida colonisation of at least three anatomical (respiratory, rectum and urinary) sites could

help in the selection of empirical antifungal therapy when nosocomial candidemia is suspected. “
“Pulmonary coccidioidomycosis is caused by inhaling airborne arthroconidia of Coccidioides, a soil-dwelling fungus endemic to the desert southwestern United States. Although uncommon, disseminated coccidioidal infection can be associated with well-defined risk factors, such as cell-mediated immunodeficiency, certain racial heritages (e.g. African or Filipino), male sex, or pregnancy. Before widespread use of computed tomography (CT), the presence or persistence of mediastinal lymphadenopathy was postulated to be a risk factor for disseminated coccidioidal infection. To investigate the use of CT scanning to identify the presence of mediastinal lymphadenopathy in patients selleck chemical with pulmonary coccidioidomycosis, and to correlate such lymphadenopathy with disseminated coccidioidal infection, we performed a retrospective review of patients with pulmonary coccidioidomycosis who were

evaluated by chest CT. Two radiologists independently interpreted 150 CT scans from patients with pulmonary coccidioidomycosis. Forty-nine patients met CT criteria for mediastinal lymphadenopathy, whereas 101 patients did not. Disseminated coccidioidal infection was observed in 5 (10%) of the 49 patients with mediastinal lymphadenopathy and in 6 of the 101 (6%; P = .34) without such adenopathy. Among patients with coccidioidomycosis, patients with mediastinal lymphadenopathy, as assessed by CT, had a higher rate of disseminated infection, but the difference was not statistically significant. “
“The results of the use of ozonised sunflower oil (OLEOZON®) in the treatment of onychomycosis, based on its known antimycotic action and good skin tolerance, by means of a controlled randomised phase III assay are presented.

Indeed, there is a strong evidence that pathogens easily adhere to the ETT made of polyvinylchloride, and following the development of organized biofilm, they translocate into the airways because of the inspiratory airflows generated by the mechanical ventilator and invasive procedures, such as bronchoscopy Liproxstatin-1 clinical trial and tracheal aspirations (Diaz-Blanco et al., 1989; Inglis et al., 1989, 1995; Feldman et al., 1999). These early studies used scanning electron microscopy (SEM), which allows the characterization

of the biofilm tridimensional structure, but lacks functional information and optical sectioning. In contrast, CLSM allows a comprehensive examination of biofilm layers at different depths, real-time imaging of developing biofilm (Yarwood et al., 2004; Gunther et al., 2009), and, with the use of selective dyes, analysis of bacterial viability (Cook et al., 2000; Kim et al., 2008). Previous studies assessing ETT biofilm through confocal microscopy have provided qualitative bacterial viability analysis, particularly after antimicrobials exposure (Cook et al., 2000; Perkins et al., 2004; Berra et al., 2008; Kim et al., 2008; Rello et al., 2010). Nevertheless, only few studies applied quantitative analysis of biofilm bacterial viability (Auty et al., 2001; Yang et al., 2008; Cairns et al., 2011), and to the best of our knowledge, quantitative bacterial viability assessment

of ETT biofilm by CLSM has never been carried out. The aim of this study was to quantitatively assess, through CLSM, bacterial viability PLX-4720 cost within ETT obtained from a pig model of severe methicillin-resistant

Staphylococcus aureus (MRSA) pneumonia, undergoing different antimicrobial therapies, to compare the bacterial killing rate achieved with each treatment. In addition, we aimed to describe structural inherent characteristics of ETT bacterial biofilm, using both CLSM and SEM. Finally, we compared the in vitro capability to form biofilm between the planktonic MRSA, inoculated into the pigs, and MRSA isolates retrieved from within the ETT. We evaluated eight 7.5-mm-internal diameter ETT (Mallinckrodt Hi-Lo®; Mallinckrodt Medical, Athlone, Ireland) obtained upon extubation of eight pigs with severe MRSA pneumonia and mechanically ventilated for 72 ± 20 h (mean ± SD; Table 1). Pigs were challenged with Oxaprozin 75 mL solution of 106 CFU mL−1 of pathogenic MRSA. Instillation of MRSA was performed through the working channel of a bronchoscope FB14-V Pentax Europe GMBH (Sistemas Integrales de Medicina SA, Madrid, Spain) and evenly distributed into every lobe of each lung. The experiment was carried out for 96 h. Animals were euthanized at the end of the 96-h study or earlier based on the severity of the infection (Martinez-Olondris et al., 2012). Four of these pigs received placebo, 0.9% saline (controls), two underwent therapy with linezolid (10 mg kg−1 every 12 h IV), and two were treated with vancomycin (15 mg kg−1 every 12 h IV).

Results: CCL2/CCR2, CXCL10/CXCR3 and CCL5/CCR1, CCR5 expression was significantly increased in the sciatic nerves of sm-EAN selleck inhibitor mice compared with controls. CCL2 was expressed on Schwann cells with CCR2 expressed on F4/80+ macrophages and CD3+ T cells. CXCL10 was expressed on endoneurial endothelial cells and within the endoneurial interstitium, with CXCR3

expressed on CD3+ T-lymphocytes. CCL5 co-localized to axons, with CCR1 and CCR5 expression on F4/80+ macrophages and rare CD3+ T cells. Conclusions: This study suggests that CCL2 expressed by Schwann cells and CXCL10 expressed by endoneurial endothelial cells may induce F4/80+ macrophage and CD3+ T cell-mediated inflammation and demyelination in sm-EAN. CCL2-CCR2 and CXCL10-CXCR3 signalling pathways are potential targets for therapeutic intervention in peripheral nerve inflammation. “
“M. Zuhayra, Y. Zhao, C. von Forstner, E. Henze, P. Gohlke, J. Culman and U. Lützen (2011) Neuropathology and Applied Neurobiology37, 738–752 Activation of cerebral peroxisome proliferator-activated receptors γ (PPARγ) reduces neuronal damage in the substantia nigra after transient focal cerebral ischaemia in the rat Aim: The function of brain

(neuronal) peroxisome proliferator-activated receptor(s) Selleckchem MI-503 γ (PPARγ) in the delayed degeneration and loss of neurones in the substantia nigra (SN) was studied in rats after transient occlusion of the middle cerebral artery (MCAO). Methods: The PPARγ agonist, pioglitazone, or vehicle was infused intracerebroventricularly over a 5-day period before, during and 5 days after MCAO (90 min). The neuronal degeneration in the SN pars reticularis (SNr) and pars compacta (SNc), the analysis of the number Progesterone of tyrosine hydroxylase-immunoreactive (TH-IR) neurones and the expression of

the PPARγ in these neurones were studied by immunohistochemistry and immunofluorescence staining. The effects of PPARγ activation on excitotoxic and oxidative neuronal damage induced by glutamate and 6-hydroxydopamine were investigated in primary cortical neurones expressing PPARγ. Results: Pioglitazone reduced the total and striatal infarct size, neuronal degeneration in both parts of the ipsilateral SN, the loss of TH-IR neurones in the SNc and increased the number of PPARγ-positive TH-IR neurones. Pioglitazone protected primary cortical neurones against oxidative and excitotoxic damage, prevented the loss of neurites and supported the formation of synaptic networks in neurones exposed to glutamate or 6-hydroxydopamine by a PPARγ-dependent mechanism. Conclusions: Activation of cerebral PPARγ confers neuroprotection after ischaemic stroke by preventing both, neuronal damage within the peri-infarct zone and delayed degeneration of neurones and neuronal death in areas remote from the site of ischaemic injury.

(B) Both cska and non-cska-TCRs are degraded in the lysosome following activation. Splenocytes, were non-activated or activated as in (A), in the absence or presence of the lysosomal inhibitor NH 4 Cl, lysed and processed as in (A) for detection of ζ and ZAP-70. (C) Accumulation of cska ζ in activated T-cells following treatment

with NH 4 Cl. Average values and standard deviation were determined from six independent experiments, using ζ expression level of non-activated, NH 4 Cl untreated samples as 100%. Figure S8. FACS gateing strategy. Fostamatinib concentration In all the FACS results presented in the paper, the first gate distinguished between live and dead/debreas cells (A). The cells were stained using anti-Thy 1.2 antibodies, which enabeled us to focuse on the T cells by gating on the positive population or on the APCs (LK cells in the mixed experiment) by focusing on the negetive population (B). The result was obtained by integreating gate 1 and gate 2 as in the presented sample presented (C). “
“Chronic myelogenous leukemia (CML) is a malignant myeloproliferative disease of hematopoietic stem cells. The disease progresses after several years from an initial chronic phase to a blast phase. Leukemia-specific T cells are regularly detected in CML patients and may be involved in the immunological control of the

disease. Here, we analyzed the role Talazoparib supplier of leukemia-specific CD8+ T cells in CML disease control and the mechanism that maintains CD8+ T-cell immunosurveillance in a retroviral-induced murine

CML model. To study antigen-specific immune responses, the glycoprotein of the lymphocytic choriomeningitis virus was used as model leukemia antigen. Leukemia-specific CTL activity was detectable in vivo in CML mice and depletion of CD8+ T cells rapidly led to disease progression. CML-specific CTL were characterized by the expression of the IL-7 receptor Rebamipide α-chain. In addition, leukemia cells produced IL-7 that was crucial for the maintenance of leukemia-specific CTL and for disease control. Therefore, CML cells maintain the specific CD8+ T-cell-mediated immune control by IL-7 secretion. This results in prolonged control of disease and probably contributes to the characteristic chronic phase of the disease. Chronic myelogenous leukemia (CML) is a malignant clonal disease originating from a pluripotent hematopoietic stem cell expressing the reciprocal translocation t(9;22), which forms the oncogenic BCR/ABL fusion protein. BCR/ABL is a constitutively activated tyrosine kinase which plays a critical role in the pathogenesis of CML. After several years and acquisition of a second genetic abnormality, the disease progresses from the chronic phase to terminal blast phase in which the patients develop an acute leukemia of either myeloid (AML) or, less frequent, lymphoid (ALL) cell type 1–3. For unknown reasons, CML seems to be the most immunogenic leukemia.

Moreover, a Phase I clinical trial was conducted of human leucocyte antigen (HLA)-mismatched reduced-intensity conditioning for unrelated donor allogeneic BMT using bortezomib, tacrolimus and methotrexate for GVHD prophylaxis. It was reported that bortezomib appeared safe, was well tolerated and

might be a novel immunomodulatory agent in allogeneic transplantation [23]. We reported recently in this journal that azithromycin (AZM), a macrolide antibiotic, blocked LPS-induced nuclear translocation of NF-κB in murine bone marrow-derived DCs and inhibited significantly their immunophenotypic and functional maturation [24]. Therefore, we hypothesize that AZM, being not only an antibiotic Ruxolitinib datasheet but also a NF-κB inhibitor, has potential as a novel drug for manipulation of allogeneic responses such as acute GVHD after BMT. In support of that, we report here, for the first time, that AZM attenuated acute GVHD in a fully allogeneic murine GVHD model. Female C57BL/6 (H-2 Kb) donor mice and BALB/c (H-2 Kd) recipient mice aged 6–12 weeks were purchased from Japan SLC, Inc. (Shizuoka, Japan). Institutional approval was obtained for all animal experimentation. Fluorescein isothiocyanate (FITC)- or phycoerythrin PF-02341066 mw (PE)-conjugated monoclonal antibodies (mAbs) used to detect cell surface expression of CD3, CD4, CD11c, CD40,

CD69, CD80, CD86, I-Ab, H-2Kb and H-2Kd by flow cytometry, as well as isotype-matched control mAbs, were purchased from BD

Pharmingen and eBioscience (San Diego, CA, USA). RPMI-1640 supplemented with 10% fetal calf serum (FCS), 5 × 10−5 M 2-mercaptoethanol (ME) and 10 mM HEPES was used as the culture medium. Mice underwent allo-BMT, as described elsewhere [25]. Briefly, recipient BALB/c oxyclozanide mice (H-2d, 11 animals in each group) received 7·5 Gy total total body irradiation (TBI). On the day of transplantation (day 0), within 24 h of irradiation recipients received a single injection of BM cells (2 × 106) and spleen cells (2 × 106) obtained from donor C57BL/6 mice (H-2b) for allogeneic BMT or BALB/c mice for syngeneic BMT through the tail vein. Recipients in each group received 100 mg/kg of azithromycin (AZM) (Pfizer Inc., Groton, CT, USA) or vehicle orally once a day from day −2 to day 2, respectively (see Fig. 1a). Survival and the degree of clinical GVHD by a scoring system as described [7, 26] were monitored once every 3 days after BMT. Skin, small intestine and liver tissues, as primary GVHD target organs, were obtained from recipients on day 7 after BMT. Sections were stained with haematoxylin and eosin. Slides were examined systematically by two of the authors (T.Y. and S.I.) using a semiquantitative scoring system, as described elsewhere [27]. Spleen cells suspended in phosphate-buffered saline (PBS) were preincubated with FcγR blocking antibody (anti-mouse CD16/CD32; BD Pharmingen) and then incubated with FITC- or PE-labelled mAbs at 4°C for 20 min.

The hybrid protein consisting of Mtb39

and Mtb32 (Mtb72F) was also found to be immunogenic and produced an enhanced Th1 response to BCG in mice but failed to reduce the bacterial load in the lungs after an aerosol challenge.71 Interestingly, the co-administration or boosting of BCG vaccination with Mtb72F conferred protection in both mouse and guinea pig models.71 Similar to Rv2626c, the Rv1860 of M. tuberculosis also elicited both a lymphoproliferative response and IFN-γ production from PBMCs, and the response was found to be different in PPD-positive healthy controls and patients with pulmonary TB;72 the protein also offered protection in guinea pigs after M. tuberculosis challenge. Rv2626c could also influence macrophage signalling ABT199 for induction of higher levels of B7·1 and B7·2 and CD-40 costimulatory molecules Raf inhibitor on the macrophage surface, which may contribute to increased T-cell proliferation, as observed in the in vitro T-cell proliferation assay. Priming of T cells by expression of costimulatory molecules, MHC molecules and the necessary cytokines is important for T-cell polarization. Although some secretory proteins of M. tuberculosis have been found to increase IL-12 production and induce a pronounced Th1 response,73,74 to the best of our knowledge, this is the first report showing that Rv2626c can both activate costimulatory signalling and

trigger induction of the cytokines IL-12 and IFN-γ. Thus, Rv2626c may be a promising T-cell vaccine candidate. The protective role of the Rv2626c protein was evident from earlier studies showing that immunization of mice with Rv2626c gave better protection against the bacilli relative to the control.31 A detailed understanding of the signalling pathway exploited by this protein will therefore be helpful in designing better therapeutics against M. tuberculosis. NB and FK thank the Council of

Scientific and Industrial Research (CSIR) and Senior Research fellow (SRF). This study was supported by a Centre of Excellence in Mycobacterium 5-Fluoracil in vitro tuberculosis Grant to SEH from the Department of Biotechnology, Ministry of Science and Technology, Government of India. SEH is a JC Bose National Fellow, Department of Science & Technology, Government of India. The authors declare that there is no conflict of interest. “
“TCR-mediated activation induces receptor microclusters that evolve to a defined immune synapse (IS). Many studies showed that actin polymerization and remodeling, which create a scaffold critical to IS formation and stabilization, are TCR mediated. However, the mechanisms controlling simultaneous TCR and actin dynamic rearrangement in the IS are yet not fully understood. Herein, we identify two novel TCR ζ-chain motifs, mediating the TCR’s direct interaction with actin and inducing actin bundling.