A Fast Data Structure for Anagrams

In this paper, we are presenting a data structure, which stores the given dictionary data in a hash table called PRIME , by using fundamental theorem on Arithmetic to generate a key for each dictionary word, and stores the word in the hash table based on the key. As compared to tree-based techniques PRIME table generates anagram for the given random word in O(1) time, time to construct a PRIME table depends on the number of words in the dictionary. If dictionary has ‘n’ words then the time to develop the PRIME table is O(n). Categories and Subject descriptors: Problem solving, search and control methods

Caerulomycin A inhibits Th2 cell activity: a possible role in the management of asthma

We have recently demonstrated that Caerulomycin A induces regulatory T cells differentiation by suppressing Th1 cells activity. The role of regulatory T cells is well established in suppressing the function of Th2 cells. Th2 cells are known to inflict the induction of the activation of asthma. Consequently, in the present study, we monitored the influence of Caerulomycin A in inhibiting the activity of Th2 cells and its impact in recuperating asthma symptoms. Interestingly, we observed that Caerulomycin A significantly suppressed the differentiation of Th2 cells, as evidenced by downregulation in the GATA-3 expression. Further, decline in the levels of IL-4, IL-5 and IL-13 cytokines and IgE was noted in the animals suffering from asthma. Furthermore, we noticed substantial suppression in the inflammatory response and number of eosinophils in the lungs. In essence, this study signifies an important therapeutic role of Caerulomycin A in asthma

Latency-associated protein Acr1 impairs dendritic cell maturation and functionality: a possible mechanism of immune evasion by Mycobacterium tuberculosis

Mycobacterium tuberculosis (M. tuberculosis) in latently infected individuals survives and thwarts the attempts of eradication by the immune system. During latency, Acr1 is predominantly expressed by the bacterium. However, whether M. tuberculosis exploits its Acr1 in impairing the host immunity remains widely unexplored. Hence, currently we have investigated the role of Acr1 in influencing the differentiation and function of dendritic cells (DCs), which play a cardinal role in innate and adaptive immunity. Therefore, for the first time, we have revealed a novel mechanism of mycobacterial Acr1 in inhibiting the maturation and differentiation of DCs by inducing tolerogenic phenotype by modulating the expression of PD-L1; Tim-3; indoleamine 2, 3-dioxygenase (IDO); and interleukin 10. Furthermore, Acr1 interferes in the differentiation of DCs by targeting STAT-6 and STAT-3 pathways. Continuous activation of STAT-3 inhibited the translocation of NF-κB in Acr1-treated DCs. Furthermore, Acr1 also augmented the induction of regulatory T cells. These DCs displayed decline in their antigen uptake capacity and reduced ability to help T cells. Interestingly, M. tuberculosis exhibited better survival in Acr1-treated DCs. Thus, this study provides a crucial insight into a strategy adopted by M. tuberculosis to survive in the host by impairing the function of DCs

Caerulomycin A suppresses the differentiation of naïve T cells and alleviates the symptoms of experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is a highly detrimental autoimmune disease of the central nervous system. There is no cure for it but the treatment typically focuses on subsiding severity and recurrence of the disease. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS. It is characterized by frequent relapses due to the generation of memory T cells. Caerulomycin A (CaeA) is known to suppress the Th1 cells, Th2 cells, and Th17 cells. Interestingly, it enhances the generation of regulatory T cells (Tregs). Th1 cells and Th17 cells are known to aggravate EAE, whereas Tregs suppress the disease symptoms. Consequently, in the current study we evaluated the influence of CaeA on EAE. Intriguingly, we observed by whole body imaging that CaeA regressed the clinical symptoms of EAE. Further, there was reduction in the pool of Th1 cells, Th17 cells, and CD8 T cells. The mechanism involved in suppressing the EAE symptoms was due to the inhibition in the generation of effector and central memory T cells and induction of the expansion of Tregs. In essence, these findings implicate that CaeA may be considered as a potent future immunosuppressive drug

Caerulomycin A Suppresses Immunity by Inhibiting T Cell Activity

<div><p>Background</p><p>Caerulomycin A (CaeA) is a known antifungal and antibiotic agent. Further, CaeA is reported to induce the expansion of regulatory T cell and prolongs the survival of skin allografts in mouse model of transplantation. In the current study, CaeA was purified and characterized from a novel species of actinomycetes, <i>Actinoalloteichus spitiensis</i>. The CaeA was identified for its novel immunosuppressive property by inhibiting <i>in vitro</i> and <i>in vivo</i> function of T cells.</p><p>Methods</p><p>Isolation, purification and characterization of CaeA were performed using High Performance Flash Chromatography (HPFC), NMR and mass spectrometry techniques. <i>In vitro</i> and <i>in vivo</i> T cell studies were conducted in mice using flowcytometry, ELISA and thymidine-[methyl-³H] incorporation.</p><p>Results</p><p>CaeA significantly suppressed T cell activation and IFN-γ secretion. Further, it inhibited the T cells function at G1 phase of cell cycle. No apoptosis was noticed by CaeA at a concentration responsible for inducing T cell retardation. Furthermore, the change in the function of B cells but not macrophages was observed. The CaeA as well exhibited substantial inhibitory activity <i>in vivo</i>.</p><p>Conclusion</p><p>This study describes for the first time novel <i>in vitro</i> and <i>in vivo</i> immunosuppressive function of CaeA on T cells and B cells. CaeA has enough potential to act as a future immunosuppressive drug.</p></div

CaeA treatment inhibits <i>in vivo</i> T cell activation.

<p>Animals immunized with antigen were treated with CaeA and suppression in the activation of T cells was examined. (A) Line diagrams designate the suppression in antigen specific T cell proliferation, measured by thymidine-[methyl-³H] incorporation; (B, C) bar diagram refers to the estimation of IFN-γ and IL-5 (pg/ml) by ELISA in the (B) serum and (C) culture SNs. Results are representative of three independent experiments. Error bars indicate mean±SD. ‘***’ specifies p<0.0001.</p

CaeA mediated immunosuppression is different from calcineurin inhibitors.

<p>CD4 T cells stimulated with anti-CD3 and CD28 Abs were incubated with CaeA and CsA and monitored for (A) IL-2 secretion; (B) modulation of the proliferation by CaeA and CsA in the presence or absence of IL-2. Data shown as mean±SE are representative of 3 independent experiments. ‘***’ signify p<0.0001 and ns as non-significant.</p

CaeA is not toxic to CD4 T cells.

<p>Purified CD4 T cells stimulated with anti-CD3 and CD28 Abs were cultured with different concentrations of CaeA for 48 h. Later, frequency of CD4 T cells undergoing apoptosis was analyzed. (A) Flowcytometric histograms represent BrdU incorporation (APO-BrdU TUNEL assay) of cells undergoing apoptosis. Diagram also shows positive control; (B) bar diagram denotes flowcytometry data of the percentage of cells undergoing apoptosis. Value in the inset of histogram depicts the percentage of cells; (C) inhibition in the proliferation of T cells by different doses of CaeA, monitored by thymidine-[methyl-³H] incorporation and expressed as cpm; (D) bar diagram signifies the reversibility in T cell proliferation after the removal of CaeA. Results expressed as percentage (A); mean±SE (B-D) are from three independent experiments. ‘*’, ‘***’ specify p<0.05, p<0.0001, respectively.</p

CaeA inhibits the production of IL-10.

<p>CD4 T cells stimulated with anti-CD3 and CD28 Abs were cultured with different concentrations of CaeA for 48 h. Later, the cytokines level was estimated by ELISA. Bar diagrams represent mean+SD of (A) IL-10; (B) TGF-β estimated in the culture supernatants. ‘*’, ‘***’ denote p<0.05, p<0.0001, respectively. Results shown are of two independent experiments.</p

CaeA suppresses T cell activation and IFN-γ secretion.

<p>CD4 T cells stimulated with anti-CD3 and CD28 Abs were incubated with indicated concentrations of CaeA for 48 h. (A) Flowcytometric histogram represents CD69 expression. Value in the inset indicates percentage; (B) bar diagram depicts decreased percentage of CD4 T cells expressing CD69; (C) ELISA data depicted as pg/ml shows decrease in IFN-γ secretion by CaeA. ‘*’ represents p<0.05. Results are representative of three independent experiments.</p