TLR1- cluster of differentiation 281

Toll-like receptor 1 (TLR1) often designated as CD281 (cluster of differentiation 281), a member of the Toll-like receptor family recognizes pathogen-associated molecular pattern with specificity for gram-positive bacteria. TLR1 is a 786-residue type I transmembrane protein with a 581-amino acid leucine-rich extracellular domain (ECD), a 23-amino acid transmembrane domain (amino acids 582 to 604), and a 181-amino acid cytoplasmic Toll homology signalling domain (1, 2). TLR1 maps to chromosome 4p14 with a calculated molecular weight of 84 kDa (3, 4). TLR1 is most closely related to TLR6 and TLR10 with 68% and 48% overall amino acid sequence identity, respectively. Among members of the TLR family, TLR1 along with TLR6 comprise the most highly conserved pair and appear to have arisen more recently during evolution through a gene duplication event. Different length transcripts presumably resulting from use of alternative polyadenylation site, and/or from alternative splicing, have been noted for TLR4.

In vivo, two different sized transcripts for TLR1 are observed suggesting that the mRNA is alternatively spliced to generate two different forms of the protein. TLR1 mRNA is ubiquitously expressed and found at higher levels than the other TLRs. Of the major leukocyte populations, TLR1 is most highly expressed by monocytes, but is also expressed by macrophages, dendritic cells (DCs), polymorphonuclear leukocytes, B, T, and NK cells. While TLR1 expression is most significantly upregulated by autocrine IL-6, it is also elevated by IFN-γß, IL-10, and TNF-α. However, TLR1 level is unaffected by exposure to both Gram-positive and Gram-negative bacteria.

TLR1 along with TLR6 functions as a co-receptor for TLR2, which confers ligand specificity and enables cell signaling. Collectively, these receptor pairs mediate immune responses to a wide variety of acylated cell wall components derived from Gram-positive bacteria, Gram-negative bacteria, mycoplasma, spirochetes, and fungi. TLR1 also heterodimerizes with TLR4, not to enhance its function, but to inhibit TLR4 activity (5, 6). Defects in the TLR1/2 signaling pathway may account for human hyporesponsiveness to OspA vaccination.

Through the reciprocal exchange of extracellular domains between the human TLRs 1 and 6, it has been revealed that TLR1/2 and TLR2/6 receptor pairs exhibit different specificities toward many microbial agonists including diacylated and triacylated lipopeptides, which is determined by the region comprised of leucine-rich repeat motifs 9–12 of these receptors. A recent finding suggests that three nonsynonymous single nucleotide polymorphisms (SNPs) are located in this region of TLR1. A variant of TLR1 based upon the SNP P315L, located in the loop of LRR motif 11 (LRR11), is greatly impaired in mediating responses to lipopeptides. The P315L SNP may predispose certain individuals to infectious diseases for which the sensing of microbial cell components by TLR1 is critical to innate immune defense (7). Thus variation in the inflammatory response to bacterial lipopeptides is regulated by a common TLR1 transmembrane domain polymorphism that could potentially impact the innate immune response and clinical susceptibility to a wide spectrum of pathogens.

Reference:

1. Janeway, C. A., Jr, R. Medzhitov. 2002. Innate immune recognition. Annu. Rev. Immunol. 20: 197-216.
2. Takeda, K., T. Kaisho, S. Akira. 2003. Toll-like receptors. Annu. Rev. Immunol. 21: 335-376.
3.Beutler, B., Z. Jiang, P. Georgel, K. Crozat, B. Croker, S. Rutschmann, X. Du, K. Hoebe. 2006. Genetic analysis of host resistance: Toll-like receptor signaling and immunity at large. Annu. Rev. Immunol. 24: 353-389.
4. Rock, F.L. et al. (1998) Proc. Natl. Acad. Sci. USA 95:588.
5. Ozinsky, A. et al. (2000) Proc. Natl. Acad. Sci. USA 97:13766.
6. Wyllie, D.H. et al. (2000) J. Immunol. 165:7125.
7. Katherine O. Omueti The Journal of Immunology, 2007, 178: 6387-6394.

Read more...

TLR10- cluster of differentiation 290

Toll-like receptor 10 (TLR10) often known as CD290 (cluster of differentiation 290), is the most recently identified human homolog of the Drosophila TOLL protein. Human TLR10 is an orphan member of the Toll-like receptor family that recognizes pathogen-associated molecular pattern. Like other members of the TLR family, TLR10 contains a signal peptide, multiple leucine-rich repeats, a cysteine-rich domain, a transmembrane domain, and a cytoplasmic TOLL interleukin-1 receptor domain. The human TLR10 gene occupies 3,269 bases arranged in three exons on the short arm of chromosome 4 (4p14) and encodes an 811-amino acid protein, approximately 50% identical to TLR1 and to TLR6. TLR10 is most closely related to TLR1 and TLR6 with 48% and 46% overall amino acid identity, respectively. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene (1).

In vivo, TLR10 mRNA expression is highest in immune system-related tissues including spleen, lymph node, thymus, tonsil. TLR10 mRNA is most highly expressed on B cells. In vitro, TLR10 is moderately upregulated by autocrine IFN-γ, IL-1β, IL-6, IL-10, and TNF-α in PMA-differentiated THP-1 cells. TLR10 mRNA expression in THP-1 cells is elevated after exposure to both Gram-positive and Gram-negative bacteria. Ex vivo, monocyte TLR10 expression increases while granulocyte expression decreases on exposure to Gram-negative bacteria. (2, 3)

Due to absent of its rat homologue, the natural ligand for TLR10 has not been identified yet. Genomic studies indicate that TLR10 is in the same locus that contains TLR1 and TLR6 and are also structurally similar to each other. It has been speculated that, like TLR1 and TLR6, TLR10 may form a heterodimer with TLR2 and thereby be sensitive to similar pathogen-associated molecular patterns (PAMPs). Recent studies have shown that TLR10 was not only able to homodimerize but also heterodimerize with TLRs 1 and 2. (1)

TLR10 has been identified as a potential asthma candidate gene because early life innate immune responses to ubiquitous inhaled allergens and PAMPs may influence asthma susceptibility and thus TLR10 genetic variation may often contributes to asthma risk. (4)

References:
1. The Journal of Immunology, 2005, 174: 2942-2950.
2. Chuang, T. & R.J. Ulevitch (2001) Biochim. Biophys. Acta 1518:157.
3. Zarember, K.A. & P.J. Godowski (2002) J. Immunol. 168:554.
4. Hornung, V. et al. (2002) J. Immunol. 168:4531.

Read more...

In Search of Putative FOXP3+ Cell Surface Markers

Despite intense interest and scrutiny focused on FOXP3 as a key protein & master transcription factor, isolating and enriching for viable FOXP3 positive cells remains a challenge. Although cell separation/staining via CD4+CD25+ selection is commonly used, this technique has limited applications. Thus, surface markers specific for FOXP3 positive cells would be invaluable research tools as they would:

• Facilitate isolation & purification of viable
Treg cells
• Distinguish naturally occurring
CD4+CD25+cells from both naive and
recently activated CD4+CD25-
nonregulatory T cells
• Allow therapeutic manipulation of
Treg cells

As the search for putative FOXP3+ markers continue, Neuropilin-1, GPR83, & FR4 have emerged as potential candidates. IMGENEX is excited to offer a panel of flow cytometric characterized antibodies against:

• Neuropilin-1 (clone 211H6.01)
• GPR83 (polyclonal)
• Folate Receptor 4 (clones 12A5 & TH6)

Flow cytometric analysis of intracellular FOXP3 (IMG-5802D) and cell surface FR4 with clone 12A5 (IMG-6217C) (left) and clone TH6 (IMG-6218C) (right) at 0.06 ug/10^6 mouse splenocytes.

Flow cytometric analysis of Neuropilin-1 in CD4+CD25+ human PBMCs using A) an isotype control & B) DDX0440 at 0.5 ug/10^6 cells. These antibodies are available in multiple sizes and conjugates.

Read more...

A Functional Contributor to Cancer Metastatic Potential

Tumor metastasis plays a key role in assessing treatment strategies and an important factor in determining patient prognosis. Not surprisingly, significant effort has been focused on elucidating the molecular basis behind tumor metastasis. This understanding may allow development of diagnostic and prognostic tools and likely provide novel therapeutic targets.

In a recent study by Crawford et al. published in PNAS, it was shown that Brd4, a ubiquitously expressed 200-kDa nuclear protein broadly expressed in many tissues, significantly reduced tumor growth and metastasis when implanted into mice. Further, Microarray analysis performed by the same group identified a correlation between Brd4 activation and disease progression/patient survival.

Together, this evidence strongly suggests that Brd4 plays a key role in breast cancer progression and an underlying mechanism of many metastasis-predictive gene signatures.

Although it remains to be determined if Brd4's role is that of a proximal factor or an intermediary molecule of some other inherited factor that drives the progression of breast cancer, its functional importance is emerging as both a diagnostic and prognostic tool with therapeutic significance.

Read more...

Neuropilin-1/BDCA-4/CD304

Neuropilin-1 (Nrp-1) was recently identified as a possible surface marker for naturally occurring CD4+CD25+ regulatory T cells and is constitutively expressed on the cell irrespective of its activation status. Nrp-1 is a type 1 membrane protein with three unique functions. In neuronal cells, Nrp-1 binds the class 3 semaphorins, which are neuronal chemorepellents, and plays a role in the directional guidance of axons. It also form complexes with the plexinA subfamily members and mediate the semaphorin-elicited inhibitory signals into neurons. Moreover in endothelial cells, Nrp-1 binds a potent endothelial cell mitogen, vascular endothelial growth factor (VEGF)165 and thus regulates vessel formation (1). The protein is also described to mediate homophilic interactions between dendritic cells and T cells in human, which confirms its role in immune function. Amongst T cells, Nrp-1 is preferentially expressed on T regulatory cells (Tregs) (2). It has been suggested that Neuropilin-1 acts as glue between Tregs and dendritic Cells (4). Neuropilin-1 expression on Tregs has been shown to enhance their interactions with immature dendritic cells (iDCs) during antigen recognition (4).

Treg cells are potential components of the immune system controlling immune responsiveness to self and alloantigens. Apart from the expression of the two surface molecules, CD4 and CD25, Treg cells are also known to express the transcription factor Foxp3, which is essential for the development and function of Treg cells. Recently, several cell surface molecules, such as, CTLA-4, GITR, LAG3, GPR83, Folate receptor 4 have been shown to be expressed at high level on regulatory T cells. Besides the currently known other cell surface receptors for Treg cells such as the B7-family members PD1, and ICOS, are also up regulated in activated non-regulatory CD4+T cells.

Recent research works to identify a specific cell surface marker for Tregs has led to identification of Nrp-1 as a cell surface molecule that is expressed by 80% of CD4+CD25+ Tregs but not on naïve cells. Further studies reveal the expression of the Nrp-1 gene to be regulated by the transcription factor Foxp3. Ectotopic expression of FoxP3 in CD4+ T cells lead to up regulation of Nrp-1 and increases interaction time between Tregs and iDCs, resulting in higher sensitivity to limiting amounts of antigens (5). Anti-Nrp-1 antibody treatment interferes with interactions between Tregs and iDCs. Moreover the expression of the protein is also significantly low in naive non-regulatory T cells (CD4+CD25- T cells) and is further down regulated after TCR stimulation. Thus Nrp-1 represents a novel surface marker on Treg cells with several important functions.

IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation, San Diego, USA. Find out more information about Neuropilin-1 (NRP-1) .

Read more...

Folate Receptor 4 (FR4)

Folates play an important role in protein and nucleic acid biosynthesis and are particularly recognized for their roles in spinal canal and brain development during early pregnancy. FR4 is expressed at high levels on both natural and TGF-b induced Tregs. The majority of CD4+ Tregs express FR4 along with CD25 and FoxP3. FR4 antibodies (e.g. clone 12A5 and TH6) recognize a subtype of the receptor (35kD) for the vitamin folic acid also known as folate receptor d, and folate-binding protein 3. Additionally, there are functional similarities in regulating immune responses between FoxP3 and FR4 expressing CD4+/CD25+ Tregs. CD4+CD25+ FR4hi cells may be used as a functional immunosuppressor Treg population which would be expected to express FoxP3. Accordingly, anti-FR4 antibodies may be useful for cell surface staining of Tregs and easy isolation by FACS or magnetic bead separation while maintaining the cells viability for subsequent down-stream applications.

Key Publication Findings
• FR4 appears to be constitutively expressed in Treg cells at a higher level than other activated or naive T cells
• Not simply a marker for natural Tregs, but functionally essential.

Read more...

TLR2- cluster of differentiation 282

Toll-like receptor 2 (TLR2), often designated as CD282 (cluster of differentiation 282) is a type I transmembrane protein belonging to the large homologous family of Toll like receptors. TLR2 acts as functional receptor for both Gram-positive and Gram-negative bacteria. Like all other members of the TLR family, TLR2 is composed of an extracellular domain containing multiple leucine-rich repeats (LRRs), a transmembrane region, and a cytoplasmic tail containing the conserved TIR domain. TLR2 maps to chromosome 4q31-32 and encodes a putative 784 amino acid protein with 19 N-terminal LLRs and a calculated molecular weight of 84 kDa (1, 2, 3). Comparison of the amino acid sequence reveals that TLR2, TLR1, and TLR6 form a TLR subfamily, which presumably diverged from one common ancestral gene. In humans, TLR10 is also a member of this TLR2 subfamily. Among all TLR, TLR1 and TLR6 have the highest identity of overall amino acid sequence, which is 66%, and a similar genomic structure and thus it is assumed that they are the evolutionary products of gene duplication.

In vivo transcripts for TLR2 are observed suggesting that the mRNA is alternatively spliced. TLR2 mRNA expression is observed in brain, heart, lung, and spleen tissues and is highest in PBLs, specifically those of myelomonocytic origin. In vitro PMA-differentiated THP-1, TLR2 is most significantly upregulated by autocrine IL-6 and TNF-α, IL-1β, and IL-10. Further, TLR2 mRNA expression is elevated after exposure to both Gram-positive and Gram-negative bacteria. The increase in TLR2 expression in monocytes and granulocytes on exposure to Gram-negative bacteria is only very modest. Furthermore, TLR2 appears to be up-regulated on mononuclear cells during disorders such as chronic obstructive pulmonary disease, influenza virus infections, and sepsis

TLR2 act as signal transducers for various bacterial components which include lipoproteins derived from M. tuberculosis, Borrelia burgdorfei, Treponema pallidium and Mycoplasma fermentans. In addition, TLR2 mediates cellular responses to a wide variety of infectious pathogens and their products which include yeast cell walls, whole mycobacteria, mycobacterial ara-lipoarabinomannan, whole Gram-positive bacteria, peptidoglycan (PGN), Treponema glycolipid and Trypanosoma cruzi glycophosphatidylinositol anchor. TLR2 forms heterodimers with TLR1, TLR6 and possibly TLR10, where each complex is particularly sensitive to subsets of TLR2-associated pathogen-associated molecular patterns (PAMPs). It has been studied that TLR6 and TLR2 function together to detect Gram-positive bacteria, PGN and zymosan, whereas TLR2 functions either alone or with TLRs other than TLR6 to detect bacterial lipopeptides. More recent studies have suggested that, like TLR4, TLR2 complexes require CD14 and MD-2 for detection of PAMPs and signaling. (4, 5) Upon ligand recognition, TLR2 recruits both the TIR domain-containing sorting adaptor TIRAP and the signaling adaptor MyD88, and initiates the MyD88-dependent pathway. The MyD88-dependent pathway activates nuclear factor (NF)-κB, activator protein-1 (AP-1) and interferon regulatory factor 5 (IRF5), which induce inflammatory cytokine expression such as IL-6, IL-12, and TNFα. (6)

Aside from detection of non-self patterns, TLR2 complexes are also capable of detecting altered self patterns, such as those displayed by necrotic cells. Further, recent evidence indicates that TLR2 is recruited to phagosomes and may be directly involved in the internalization of microbial products by cells.

Reference:
1. Rock, F.L. et al. (1998) Proc. Natl. Acad. Sci. USA 95:588.
2. Chaudhary, P.M. et al. (1998) Blood 91:4020.
3. Dunne, A. & L.A.J. O'Neill (2003) Sci. STKE 2003:re3.
4. Modlin, R.L. (2002) Ann. Allergy Asthma Immunol. 88:543.
5. J Endotoxin Res. 2000;6(5):401-5
6. Annual Review of Biochemistry Vol. 76: 447-480 (Publication date July 2007)

Read more...

TLR3- cluster of differentiation 283

Toll-like receptor 3 (TLR3) often designated as CD283 (cluster of differentiation 283) is a type I transmembrane receptor protein. It belongs to a family of evolutionary conserved innate immune recognition molecules and recognizes double-stranded RNA, a molecular pattern associated with viral infections. Like all other members of the TLR family, TLR3 is composed of an extracellular domain containing multiple leucine-rich repeats (LRRs), a transmembrane region, and a cytoplasmic tail containing the conserved TIR domain. The transmembrane domain consists of a single alpha-helix spanning the membrane, while the TIR domain is made up of a five-stranded beta-sheet surrounded by five alpha-helices. The human TLR3 ectodomain structure at 2.1 angstroms reveals a large horseshoe-shaped solenoid assembled from 23 LRRs (1). The TLR3 gene maps to chromosome 4q35 and its sequence encodes a putative 904 amino acid protein and a calculated molecular weight of 97 kDa. TLR3 is most closely related to TLR5, TLR7, and TLR8, each with 26% overall amino acid sequence identity. In vivo, two different sized transcripts for TLR3 are observed suggesting that the mRNA is alternatively spliced to generate two different forms of the protein.

TLR3 mRNA is expressed at highest levels in placenta and pancreas. There are conflicting reports regarding the expression of TLR3 in particular leukocyte populations. Some suggest that TLR3 is only expressed by dendritic cells while others find that TLR3 is expressed by T or NK cells. In vitro, PMA-differentiated THP-1 TLR3 is moderately upregulated by autocrine IFN-γ, IL-1ß, IL-6, IL-10, and TNF-α. Further, TLR3 mRNA is elevated after exposure to Gram-negative bacteria and to an even greater extent in response to Gram-positive bacteria. Ex vivo, TLR3 expression is elevated in both monocytes and granulocytes upon exposure to Gram-negative bacteria. TLR3 is usually localized intracellularly, perhaps to the lysosomal compartment or at the cell surface. However the localization of TLR3 is cell type dependent.

Human TLR3 recognizes foreign-derived double-stranded RNA of certain viruses like influenza, endogenous necrotic cell RNA and polyinosinic acid as ligands. Stimulation of the receptor by the ligand induces the activation of NF-kappaB and the production of type I interferons (IFNs) which signal other cells to increase their antiviral defenses (2). TLR3 relies on a TIR domain-containing adaptor inducing IFN-beta (TRIF)-mediated pathway for the production of IFN- in response to pathogen recognition. Trif contains a RIP homotypic interaction motif (RHIM) at the C terminus that is essential for binding of RIP1 and RIP3, two serine-threonine kinases linked to tumor necrosis factor (TNF)−mediated NF- B activation. (3, 4, 5). Activation of TLR3 leads to recruitment of receptor-interacting protein 1, TRAF3 and TRAF6, which activates TRAF family member-associated NF- B activator-binding kinase 1 (TBK1) andr inducible I B kinase (IKK-i), which directly phosphorylate IRF3 and IRF7 for the production of type-I IFN cytokines.(6)

TLR3 has been implicated in various viral infections of the respiratory tract and in central nervous system (CNS) diseases. On the contrary it positively contributes to the immune response to invading encephalomyocarditis virus. TLR3 has also been implicated in the protection against herpes simplex virus type 2 infection of the female genital tract. Recent work on TLR3 reveals its role in the immunobiology of skeletal muscle (7).

Reference:
1. J Endotoxin Res. 2006; 12(6):375-8
2. Nature. 2001 Oct 18; 413(6857):732-8
3. Nature Immunology 5, 503 - 507 (2004)
4.Rock, F.L. et al. (1998) Proc. Natl. Acad. Sci. USA 95:588.
5. Science. 2005 Jul 22; 309(5734):581-5. Epub 2005 Jun 16
6.Oncogene (2008) 27, 181–189; doi:10.1038/sj.onc.1210906
7. Clinical Microbiology Reviews, January 2008, p. 13-25, Vol. 21, No. 1

IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation, San Diego, USA. Find out more information about Toll-like receptors .

Read more...

TLR4- cluster of differentiation 284

Toll-like receptor 4 (TLR4) often designated as CD284 (cluster of differentiation 284) is a class I transmembrane receptor belonging to the large homologous family of Toll like receptors. TLR4 expressed on the surface of immune system cells, is activated by exposure to lipopolysaccharides derived from the outer membrane of Gram negative bacteria and thus forms part of the innate immune response in mammals. (1) TLR4 was initially cloned as the human homolog of Drosophila Toll (dToll) and thus was first named hToll. Like all other members of the TLR family, TLR4 is composed of an extracellular domain containing multiple leucine-rich repeats (LRRs), a transmembrane region, and a cytoplasmic tail containing the conserved TIR domain. TLR4 maps to chromosome 9q32-33. It shows a high degree of similarity to dToll over the entire aminoacid sequence. The TLR4 sequence encodes an 839 aminoacid protein with 22 N-terminal LRR regions and a calculated molecular weight of 90 kDa. TLR4 is most closely related to TLR1 and TLR6 each with 25% overall aa sequence identity. Several transcript variants of this gene have been found, but the protein coding potential of most of them is uncertain.

In vivo, TLR4 mRNA is expressed as a single transcript, and found at highest levels in spleen and PBLs. (2, 3) Of the PBL populations, TLR4 is expressed by B cells, DCs, monocytes, macrophages, granulocytes, and T cells. Other reports suggest that TLR4 is only expressed in myelomonocytic cells and is highest in mononuclear cells. In vitro, TLR4 mRNA and protein expression is upregulated in THP-1 cells upon PMA-induced differentiation. TLR4 is moderately upregulated by autocrine IFN-γ, IL-1β. TLR4 mRNA expression in THP-1 cells is unaffected by exposure to both Gram-positive and Gram-negative bacteria. Ex vivo, granulocyte, and especially monocyte, TLR4 expression is upregulated upon exposure to Gram-negative bacteria. (4)

TLR4 is critical for host defense against gram-negative bacteria in both mice and humans. Upon recognition of its ligand LPS, TLR4 undergoes dimerization, and recent studies suggest that this causes concerted conformational changes in the receptor leading to self association of the cytoplasmic Toll/Interleukin 1 receptor (TIR) signalling domain. Ligand recognition by TLR4 requires the extracellular association of an additional component, MD-2 which together can initiate two major intracellular signaling pathways, MyD88-dependent and TRIF-dependent (MyD88-independent). The MyD88-dependent pathway requires the recruitment of TIRAP and MyD88 via homophilic TIR-TIR interactions and activates nuclear factor (NF)-κB, activator protein-1 (AP-1) and interferon regulatory factor 5 (IRF5), which induce inflammatory cytokine expression such as IL-6, IL-12, and TNFα. The TRIF-dependent pathway requires the recruitment of TRAM and TRIF and activates IRF3, in addition to NF-κB and AP-1, which induce type I interferon (IFN) expression. TLR4 can also activate various other signaling molecules, including phosphatidylinositol-3 kinase (PI-3K) and MAP3Ks such as MEKK3, TPL2, and ASK1. (5,6) The TLR4 complex also recognizes a few other bacterial PAMPs including LTA. Further, the TLR4 complex recognizes viruses including respiratory syncytial virus (RSV), hepatitis C virus (HCV), and mouse mammary tumor virus (MMTV). The TLR4 complex can also recognize endogenous ligands, for example, heat shock proteins, fibrinogen, fibronectin, surfactant protein A (SP-A), and β-defensins. TLR4 also forms heterodimers both with TLR5, which presumably enhances its activity, and also with TLR1, which inhibits its activity. (7, 8)

Mutations in TLR4 gene have been associated with differences in LPS responsiveness.
A recently discovered Asp299Gly TLR4 polymorphism has been identified that confer differences in the inflammatory response elicited by bacterial lipopolysaccharide and is associated with a decreased risk of atherosclerosis. (9)

Reference:
1. Ricardo et al. PLoS ONE. 2007; 2(8): e788.
2. Medzhitov, R. et al. (1997) Nature 388:394.
3. Rock, F.L. et al. (1998) Proc. Natl. Acad. Sci. USA 95:588.
4. Zarember, K.A. & P.J. Godowski (2002) J. Immunol. 168:554.
5. Myeong Sup Lee Vol. 76: 447-480 Annual Review of Biochemistry
6. Yong-Chen Lu doi:10.1016/j.cyto.2008.01.006 Article in press
7. Spitzer, J.H. et al. (2002) Eur. J. Immunol. 32:1182.
8. Mizel, S.B. et al. (2003) J. Immunol. 170:6217.
9. N Engl J Med 2002; 347:1978-1980, Dec 12, 2002.

Read more...

TLR5- cluster of differentiation 285

Toll-like receptor 5 (TLR5), a member of the evolutionarily conserved Toll-like receptor family, has evolved to permit mammals specifically to detect flagellated bacterial pathogens. Like all other members of the TLR family, TLR5 is composed of an extracellular domain containing multiple leucine-rich repeats (LRRs), a transmembrane region, and a cytoplasmic tail containing the conserved TIR domain. The TLR5 gene has been mapped to chromosome 1q41-42. The gene encodes a putative 858 aminio acid protein with a calculated molecular weight of 91 kDa. It is most closely related to TLR3 with 26% overall amino acid sequence identity.

In vivo, TLR5 mRNA is expressed as a single transcript in ovary, prostate. In vitro, TLR5 is most significantly upregulated in PMA-differentiated THP-1 cells by autocrine IL-6, IL-10, and TNF-α, but is also elevated by IFN-γβ. Further, TLR5 mRNA expression is elevated after exposure to both Gram-positive and Gram-negative bacteria. Ex vivo, however, granulocyte and in particular monocyte TLR5 expression is downregulated upon exposure to Gram-negative bacteria (1, 2).

TLR5 is expressed in epithelial cells of the airways, intestine, and urogenital tract, as well as on hemopoietic cells of the innate and adaptive immune system and has recently been shown to be involved in the transport of flagellated Salmonella typhimurium from the intestinal tract to the mesenteric lymph nodes. Like other described TLRs, TLR5 utilizes the adaptor protein MyD88 and IL-1 receptor-associated kinase (IRAK) to activate a signal transduction cascade that results in the activation of the transcription factor NF- B necessary for flagellin-induced effects on gene expression (4). TLR5 forms a homodimer as well as a heterodimer with TLR4. Both complexes function to recognize the Flagellin protein of both Gram-positive and Gram-negative bacteria, and activation of the receptor mobilizes the nuclear factor NF-kappaB and stimulates tumour necrosis factor-alpha production. TheTLR5 recognition site on flagellin is conserved among a wide variety of flagellated bacteria although select bacterial species possess unique flagellin molecules that evade TLR5 recognition. These amino acids are located in the highly conserved D1 domain of the flagellin protein and cluster on the convex surface that contacts adjacent flagellin monomers in the flagellar protofilament. Mutating individual residues in the TLR5 recognition site significantly reduced or completely abolished bacterial motility, suggesting that evolving a functional flagellin that evades TLR5 would require a complex series of mutations (5).

Reference:
1. Zarember, K.A. & P.J. Godowski (2002) J. Immunol. 168:554.
2. Muzio, M. et al. (2000) J. Immunol. 164:5998.
3. Yimin Yu Am J Physiol Gastrointest Liver Physiol 285: G282-G290, 2003
4. Nature. 2001 Apr 26;410(6832):1099-103.

Read more...

TLR6- cluster of differentiation 286

Toll-like receptor 6 (TLR6) often designated as CD286 (cluster of differentiation 286), is a member of the Toll-like receptor family, a highly conserved series of ancient innate immune pattern recognition receptors. TLR6 was first described by Takeuchi et al in 1999 as a 91.9-kDa, 796 amino-acid polypeptide. The gene for TLR6 has been mapped to human chromosome 4p13. It has a single exon, and contains an N-terminal signal peptide, 20 tandemly repeated extracellular leucine-rich motifs, and a cytoplasmic domain homologous to interleukin-1 receptor (IL1R), similar to other TLRs (1). TLR6 is most closely related to TLR1, TLR10, and TLR2 with 68%, 46%, and 31% overall AA sequence identity, respectively. (2)

In vivo, TLR6 transcript is observed in thymus, spleen, and lung. TLR6 mRNA expression is highest in B cells and monocytes. In vitro, TLR6 mRNA expression is upregulated in THP-1 cells upon PMA-induced differentiation. Further, TLR6 is moderately upregulated by autocrine IFN-γ, IL-1β. However, TLR6 mRNA expression in THP-1 cells is unaffected by exposure to both Gram-positive and Gram-negative bacteria. Ex vivo, monocyte and, in particular, granulocyte TLR6 expression is down-regulated upon exposure to Gram-negative bacteria. (3, 4, 5).

Coexpression of TLR2 and TLR6 at the cell surface is crucial for recognition of diacylated lipopeptide and peptidoglycan and subsequent cellular activation in human cells. TLR6 was expressed, although at a lower level than TLR2, on the cell surface in monocytes, monocyte-derived iDCs, and neutrophils, but not on B, T, or NK cells. Confocal microscopic analysis revealed that TLR6 was colocalized with TLR2 at the plasma membrane of monocytes (6). Like TLR1, TLR6 is thought to specify or enhance the pathogen-associated molecular patterns (PAMP) sensitivity of TLR2 and contribute to its signaling capabilities through heterodimerization. TLR2/6 heterodimers recognize diacyl lipopeptides such as MALP2 (the Mycoplasma-derived macrophage-activating lipopeptide 2). CD14 was reported to enhance the responses of TLR2/TLR6 complexes to their ligands. CD36 helps TLR2/6 to further discriminate among their ligands because it contributes to the response to MALP2 and lipoteichoic acid (from gram-positive bacteria), but not to zymosan. Upon ligand recognition, TLR2/TLR6 complexes recruit both the sorting adaptor TIRAP and the signaling adaptor MyD88, and initiate the MyD88-dependent pathway, activating the transcription factors nuclear factor (NF)-κB and activator protein-1 (AP-1), leading to inflammatory cytokine production. (7)

Reference:
1. K Tantisira Genes and Immunity (2004) 5, 343–346.
2. O. Takeuchi Gene (1999) Volume 231, Issues 1-2, 29,pp 59-65
3. Takeuchi, O. et al. (1999) Gene 231:59.
4. Zarember, K.A. & P.J. Godowski (2002) J. Immunol. 168:554.
5. Hornung, V. et al. (2002) J. Immunol. 168:4531.
6. Yoshiya Nakao (2005) The Journal of Immunology, 174: 1566-1573.
7. Myeong Sup Lee (2007) Annual Review of Biochemistry Vol. 76: 447-480.

Read more...

TLR7- cluster of differentiation 287

Toll-like receptor 7 (TLR7), is an immune gene possessed by humans, other mammals and additionally in avian species playing a significant role in initiating antiviral immune responses. It belongs to the evolutionarily conserved Toll-like receptor family. The TLR7 sequence encodes a 1049 amino acid protein with a calculated molecular weight of 121 kDa. Like all other members of the TLR family, TLR7 contain an ectodomain with multiple leucine-rich repeats (LRRs) and a cytoplasmic domain homologous to that of the human interleukin-1 (IL-1) receptor. TLR7 is most closely related to TLR8 and TLR9 with 43% and 36% overall amino acid sequence identity, respectively and thus along with TLR8 and TLR9 constitutes a new sub-family of the TLRs.

In vivo, TLR7 mRNA is expressed in lung, placenta, spleen, lymph node, and tonsil. TLR7 mRNA expression is highest in monocytes, B cells, and DC. In vitro, TLR7 mRNA expression is upregulated in THP-1 cells upon PMA-induced differentiation. TLR7 is highly upregulated by exposure to IL-6 and to a slightly lesser extent by autocrine IFN-γ, IL-1β. TLR7 mRNA expression in THP-1 cells is elevated after exposure to both Gram-positive and Gram-negative bacteria. Ex vivo, expression of TLR7 is elevated after exposure to both Gram-positive and Gram-negative bacteria in monocytes and to a greater degree in granulocytes. Like TLR3, it appears that TLR7 may be localized intracellularly (1, 2). In humans, TLR7 is expressed on a restricted range of cell types with the highest abundance found on plasmacytoid dendritic cells and B cells.

TLR7 is activated by infections with single-stranded RNA viruses, including influenza virus and vesicular stomatitis virus (VSV). Stimulation of TLR7 with the viral nucleic acids, causes a type I IFN response and secretion of a large quantity of IFNα and the production of inflammatory cytokines [including IFN-alpha, IFN-beta, interleukin-6 (IL-6), IL-12, tumour necrosis factor-alpha (TNF-alpha)]. TLR7 activation also mediates up-regulation of costimulatory molecules (CD40, CD80, CD86), major histocompatibilty complex molecules and chemokine receptors (CCR7) (3). Two signaling pathways of TLR7 are thought to induce inflammatory cytokine expression: the MyD88- IRAK1-TRAF6-IRF5 pathway and the MyD88-TRAF6-TAK1-MAPK/IKK-AP-1/NF-κB pathway.(4) Following nucleic acid recognition, TLR7 recruit the TIR-domain
containing adapter called MyD88. MyD88 forms a complex with members of IRAK family
(IRAK1 and IRAK4) and TRAF6, which in turn activates TAK1 and results in the activation of NF-κB. In addition to single-stranded RNA, the synthetic imidazoquinoline, imiquimod, a low molecular weight immune response modifier, activates TLR7 in both humans and mice, whereas its derivative resiquimod (R-848) activates TLR7 in humans. Both imiquimod and R-848 elicit robust anti-viral and anti-tumor immune responses in vivo, which correlate with a strong induction of type I IFNs. As a consequence of this activity, imiquimod is used for the treatment of external genital warts caused by human Papillomavirus. (5) TLR7 has been implicated in recognizing guanosine and uracil-rich single-stranded(ss) RNA such as the U5 region of human immunodeficiency virus type 1 RNA and influenza U-rich ssRNA, leading to up-regulation of IFN-alpha.

Reference:
1. Heine, H. & E. Lein (2003) Int. Arch. Allergy Immunol. 130:180.
2. Dunne, A. & L.A.J. O'Neill (2003) Sci. STKE 2003:re3.
3. Victoria J Volume 114 Issue 4 Page 507-521, April 2005
4. Myeong Sup Lee Annual Review of BiochemistryVol. 76: 447-480, 2007.
5. Annett Schoenemeyer J. Biol. Chem., Vol. 280, Issue 17, 17005-17012, April 29, 2005.

IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation, San Diego, USA. Find out more information about Toll-like receptors .

Read more...

TLR8- cluster of differentiation 288

Toll-like receptor 8 (TLR8) often designated as CD288 (cluster of differentiation 288) is a member of evolutionarily conserved Toll-like receptor family which are critical parts of the evolutionarily conserved innate immune system. TLR8 has been identified as natural receptor for single-stranded RNA, and is thought to act as potent activator of innate immune responses upon viral infections. Like all other members of the TLR family, TLR8 is composed of an extracellular domain containing multiple leucine-rich repeats (LRRs), a transmembrane region, and a cytoplasmic tail containing the conserved TIR domain. The TLR8 sequence encodes a 1041 amino acid protein containing 26 N-terminal leucine rich repeats with a calculated molecular weight of 120 kDa. The gene for TLR8 has been mapped to chromosome Xp22. TLR8 is most closely related to TLR7 and TLR9 with 43% and 35% overall amino acid sequence identity, respectively and together they constitute one of the six major TLR clades. (1,2)

In vivo, TLR8 mRNA is expressed in lung, placenta, spleen, lymph node, bone marrow, and PBLs, with highest expression found in monocytes. In vitro, TLR8 mRNA expression is upregulated in THP-1 cells upon PMA-induced differentiation. TLR8 is highly upregulated by autocrine IL-1β, IL-6, IL-10, and TNF-α, and is even more enhanced by exposure to IFN-γ. TLR8 mRNA expression in THP-1 cells is elevated after exposure to both Gram-positive and Gram-negative bacteria. Ex vivo, monocyte TLR8 expression increases while granulocyte expression decreases on exposure to Gram-negative bacteria. (3) Like TLR7 and TLR7, TLR8 is exclusively localized to intracellular
compartments like endosomes, suggesting that these intracellular TLRs recognize
nucleic acids following the internalization and lysing of viruses.

Human TLR8 preferentially mediates the recognition of human immunodeficiency virus, vesicular stomatitis virus, and influenza virus-derived guanosine or uridine rich ss RNA and a synthetic compound (imidazoquinoline compound R848) with antiviral activity R-848. Following nucleic acid recognition, TLR8 recruit the TIR-domain containing adapter called MyD88. MyD88 forms a complex with members of IRAK family (IRAK1 and IRAK4) and TRAF6, which in turn activates TAK1 and results in the activation of NF-κB and synthesis of type I interferons.(4)

A novel role for TLR8 as a suppressor of neurite outgrowth as well as an inducer of neuronal apoptosis has been found. Reports suggest that TLR8 functions in neurons through an NF-kappaB-independent mechanism (5). Recent studies also reveal that the human TLR8 signaling pathway is essential for reversing the function of Treg cells that play a critical role in suppressing immune responses and inducing immune tolerance to cancer and infectious diseases. Thus, the combination of peptide-based vaccines with a TLR8 agonist, may greatly improve the therapeutic potential of cancer vaccines. (4)

Reference:
1. Chuang, T.H. & R.J. Ulevitch (2000) Eur. Cytokine Netw. 11:372.
2. Dunne, A. & L.A.J. O'Neill (2003) Sci. STKE 2003:re3.
3. Heine, H. & E. Lein (2003) Int. Arch. Allergy Immunol. 130:180.

4. Oncogene (2008) 27, 190–199; doi:10.1038/sj.onc.1210913
5. Cell Cycle. 2007 Sep;6(23):2859-68. Epub 2007 Sep 4

IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation, San Diego, USA. Find out more information about Toll-like receptors .

Read more...

TLR9- cluster of differentiation 289

Toll-like receptor 9 (TLR9) often known as CD289 (cluster of differentiation 289), is a member of the Toll-like receptor family that recognizes pathogen-associated molecular pattern. TLR9 was first cloned and identified as a receptor for unmethylated CpG-DNA as well as for bacterial DNA. It is essential not only for pro-inflammatory cytokine production and other inflammatory responses, but it also plays a role in the induction of T helper 1 (Th1) acquired immune response and in the proliferation of B cells. Like all other members of the TLR family, TLR9 is composed of an extracellular domain containing multiple leucine-rich repeats (LRRs), a transmembrane region, and a cytoplasmic tail containing the conserved TIR domain. The TLR9 sequence encodes a 1032 aa protein containing 27 N-terminal LRRs with a calculated molecular weight of 116 kDa . The gene for TLR9 has been mapped to human chromosome 3p21.3. TLR9 is most closely related to TLR7 and TLR8 with 36% and 35% overall amino acid sequence identity, respectively and thus along with TLR7 and TLR8 constitutes a new sub-family of the TLRs.

In vivo, TLR9 mRNA is expressed in spleen, lymph node, bone marrow, and PBLs. (1) Specifically, TLR9 mRNA is expressed at the highest levels in B cells and dendritic cells (DC). In vitro, TLR9 is moderately upregulated by autocrine IFN-γ, IL-1ß, IL-6, IL-10, and TNF-α in PMA-differentiated THP-1 cells. TLR9 mRNA expression in THP-1 cells is unaffected by exposure to both Gram-positive and Gram-negative bacteria. Ex vivo, TLR9 expression in monocytes and particularly in granulocytes is downregulated in response to Gram-negative bacteria. (2, 3) TLR9 also appears to be localized internally, perhaps in lysosomic or endocytic compartments where it would more likely encounter PAMPs including unmethylated DNA.

TLR9 is expressed primarily on antigen presenting cells such as B cells and DC. In human DC, TLR9 is restricted to a subset of DC, plasmacytoid DC, responsible for production of high levels of type I IFN (IFNalpha). TLR9 recognizes synthetic CpG oligonucleotides and unmethylated CpG motifs in bacterial and viral DNA. Phagocytes endocytose microorganisms and lyse them in phagolysosomes, where their DNA is released and presumably interacts with TLR9, initiating an inflammatory response resulting in rapid secretion of a large quantity of IFNα and the production of inflammatory cytokines.(4) Two signaling pathways of TLR9 are thought to induce inflammatory cytokine expression: the MyD88-TRAF6-IRF5 pathway and the MyD88-TRAF6-TAK1-MAPK/IKK-AP-1/NF-κB pathway. Further TLR9 induce IFNα expression by activating IRF7 via TNF receptor-associated factor 3. The cytosolic TIR domain of TLR9 recruits the adaptor molecule MyD88 and other signaling molecules such as IRAK-4, and TRAF6 that are required for the signaling complex. The transcription factors such as IRF-1, IRF-5, and IRF-7 are also recruited to the complex and activated. The complex in turn activates other signaling cascades that lead to the activation of NF-κB and AP-1. These activated transcription factors induce diverse immunity-related genes (5).

TLR9 signaling is recently implicated in the pathogenesis of autoimmunity, especially in systemic lupus erythematosus (SLE). TLR9 can suppress the pathology of autoimmunity in certain cases, although it may also act as a trigger and a center for a feedback loop of autoimmunity.

Reference: 1. Chuang, T.H. & R.J. Ulevitch (2000) Eur. Cytokine Netw. 11:372.
2. Zarember, K.A. & P.J. Godowski (2002) J. Immunol. 168:554.
3. Hornung, V. et al. (2002) J. Immunol. 168:4531.
4. Cynthia A. Leifer The Journal of Immunology, 2004, 173: 1179-1183.
5. Yutaro Kumagai doi:10.1016/j.addr.2007.12.004 Article in press 2008.

IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation, San Diego, USA. Find out more information about Toll-like receptors .

Read more...

YOGA

Yoga is a perfect practical system of self-culture. Yoga is an exact science. It aims at the harmonious development of the body, the mind and the soul. Yoga is the turning away of the senses from the objective universe and the concentration of the mind within. Yoga is eternal life in the soul or spirit. Yoga aims at controlling the mind and its modifications. The path of Yoga is an inner path whose gateway is your heart.
It helps in the co-ordination and control of the subtle forces within the body. Yoga brings in perfection, peace and everlasting happiness. Yoga can help you in your business and in your daily life. You can have calmness of mind at all times by the practice of Yoga. You can have restful sleep. You can have increased energy, vigour, vitality, longevity and a high standard of health. Yoga transmutes animal nature into divine nature and raises you to the pinnacle of divine glory and splendor.
The regular practice of Yoga will help you to control the emotions and passions and will give you power to resist temptations and to remove the disturbing elements form mind. It will enable you to keep a balanced mind always and remove fatigue. It will confer on you serenity, calmness and wonderful concentration. It will enable you to hold communion with the Lord.
However, to attain success in Yoga, it is very necessary to abandon all worldly enjoyments and practice Tapas and Brahmacharya. You will have to control the mind skillfully and tactfully. You will have to use judicious and intelligent methods to curb it. If you use force, it will become more turbulent and mischievous. It cannot be controlled by force. It will jump and drift away more and more. Those who attempt to control the mind by force are like those who endeavour to bind a furious elephant with a thin silken thread.
Yoga, therefore, presents a system of liberating the spiritual essence from this involvement, this entanglement in mental and physical processes. It achieves the effect of restoring the spiritual consciousness to its pristine state, pure original state. The thesis of Yoga is based upon the direct experience of those who became its expounders, is that your true nature, your real and essential nature, is pure bliss. It is pure peace. It is Ananda and Santi. Not sorrow. Not misery. Not grief. Not restlessness. Not agitation. Not tears. But peace and joy. It is necessary, at the outset, to clear certain misconceptions in regard to Yoga, prevalent especially among some sections in the West. Yoga is not magic or a feat of any kind, physical or mental. Yoga is based on a sound philosophy and deep psychology. It is an educational process by which the human mind is trained to become more and more natural and weaned from the unnatural conditions of life. Yoga has particular concern with psychology, and, as a study of the 'self', it transcends both general and abnormal psychology, and leads one to the supernormal level of life. In Yoga we study ourselves, while in our colleges we are told to study objects.
The purpose of Yoga is to try to restore to man his pristine state of perfect bliss; and this it
does by liberating the human individual from his involvement in body, senses and mind. This involvement itself is the prime cause for keeping him away from itself, is the greatest obstacle to his attainment of that experience which the Yoga science says lies right here, present at this moment. To become liberated from the bondage of pain, thus bringing to an end the union of man's nature with pain, is Yoga.

Read more...

Yoga for Children: How to Get Your Kids on the Mat

If you’re like me, I discovered yoga in college and haven’t been able to get enough since. I remember arriving at my first yoga class with my new yoga mat and no expectations. To my surprise, what I found was an invigorating source of exercise that stretched and strengthened my body in a way that no other exercise I’d tried had, combined with calming my body and mind so completely that I’d often nearly fall asleep during final relaxation. My love for yoga has only grown over the years, so when I had children, as soon as they could stand I started thinking of ways I could incorporate yoga into their lives. I believe that yoga for children offers as many benefits for my children as it does to me, if not more. Whether you’re planning on introducing your children to yoga with a kids yoga dvd or you’re planning on bringing yoga in the classroom using your own knowledge of the poses, the following are some tips I’ve found helpful in introducing yoga for children into the lives of my kids.

First, take your child shopping for their very own yoga mat and maybe even some additional yoga gear. Yoga mats today come in a variety of colors and sizes, and kids love having choices, so let them select the one that suits them best. You may even buy some comfortable clothing suitable for yoga practice, as well as a yoga bag if they’re planning on practicing yoga in the classroom and will need to transport their mat and yoga clothing.

Consider purchasing a kids yoga DVD. Marsha Wenig, creator of YogaKids DVDs, is an award-winning yoga instructor and an expert on yoga for children. If you purchase a YogaKids kids yoga DVD, she leads children through a series of yoga poses inspired by animals, including stretching like a puppy and perching like a flamingo. The original music encourages kids to sing along while they move through the yoga poses.

Doing yoga along with your children is a great way to keep them interested and to spend time together. They’ll appreciate you going through the yoga poses along with them on your own mat. Establish a certain time each day when you and your children can practice yoga together. Start with shorter spurts at first to keep attention, and you can always extend the session later.

Yoga for children is all about teaching the poses and having fun, so encourage your children to ask questions as they flow through the poses. Keeping it playlike and fun means letting them giggle when their body is twisted into silly positions and keeping the atmosphere light and fun. It doesn’t have to be quiet like your yoga classes, so prompt children to bark like a dog in downward dog and pucker their lips when they’re in fish pose, and they’ll likely have much more fun.

Finally, to help reinforce a consistent routine with your children, consider making a calendar and encouraging your child to add a sticker to the calendar every time they complete a yoga session. Every time they follow along with their kids yoga DVD, for example, they can add a sticker, and every time they accumulate a certain number of stickers they can get a reward.

Read more...

The Secret to Living with Allergies Part 6: Allergy Relief Bed Encasings, Tips for a Healthier Night

If you’ve ever wondered why you regularly wake up sneezing, with watery eyes or feeling congested, you may have dust mite allergies. Over a million dust mites can live in a single bed, and all night, you can be breathing in dust mite allergens while you sleep that cause allergy symptoms. Dust mites are microscopic, and unlike bed bugs, they cannot be seen by the naked eye. Dust mites thrive in warm, dark and humid environments such as your pillow, mattress, blanket, carpet and upholstered furniture. Allergies are not caused by the mite being inhaled.

Instead, you are reacting to allergens created by dust mite waste particles and their dead body fragments. The large number of dust mites in the bed create a high concentration of dust mite allergens, which in turn cause symptoms for allergy sufferers. Allergy encasings act as a barrier to trap allergens within the bed and keep you from inhaling these problematic allergens while you sleep.

Step 1: How are Allergy Bed Encasings Designed to Help You?

If you’re an allergy sufferer, you may be one of many people that don’t start the morning off right, after having inhaled allergens all night long from your bed. A stuffy nose, itchy eyes, sneezing and congestion are a few of the allergy symptoms that can occur regularly as allergens are inhaled from the bed. Zipping an allergy bed encasing completely around the pillow, mattress, box spring or any other stuffed bedding can protect you from these allergens as the encasing traps allergens within the bedding.

Allergens cannot become airborne, creating a healthier sleeping environment. The National Institutes of Health (NIH) outlines “Guidelines for Allergy & Asthma Prevention,” and these guidelines recommend encasing your pillow and mattress as one of the most important steps for allergen avoidance.

Step 2: Understanding the Basics of Allergy Bed Encasings

Encasings are simple to use on your bed, although many people may not understand the basics of how allergy bed encasings work. Today’s encasings are no longer the plastic or vinyl encasings that many people may think of. Quality encasings are made from highly effective and comfortable materials that can result in no loss of sleeping comfort.

Membrane or Membrane-Free Encasings: Choices in allergy bed encasings include membrane encasings, which feature a urethane membrane lining and an upper layer of fabric, or membrane-free encasings that are made from special, high-performance fabrics that are tightly woven to block allergen particles.

Pore Size: The pore size of an allergy encasing is important, as it indicates the size of the space between the tightly woven fabric threads. A higher pore size means that the encasing can only block larger allergen particles, while a smaller pore size provides more effective protection from much smaller allergen particles. Dust mite allergens can be approximately 10 microns in size, and therefore, an encasing should have a pore size lower than 10 microns for effective relief. Pet dander is a much smaller allergen particle, and a pore size below approximately 5-6 microns is essential for effective allergen protection of pet dander and dust mite allergens.

Membrane encasings with a full urethane lining do not have pores as the membrane is “monolithic” or uniform across each surface. Although membrane encasings are highly effective at blocking allergens, they lack the breathability, superior comfort and easy care of membrane-free encasings. High performance, Allergy Control membrane-free encasings are made from very tightly woven fabrics with small pore sizes to keep allergen particles contained within the bed.

Durable Construction: All encasings are not made the same way. Many are mass-produced and are poorly made. Encasings made with superior quality features include high quality zippers for extra durability and the prevention of allergen leakage. Flaps at the zipper trap allergen particles, and bound seams re-enforce edges for long-term durability.

Comfort and Easy Care: Allergen encasings made from special cotton or polyester fabrics offer superior comfort and often have the feel of fine linens. With no loss in sleeping comfort, these allergy bed encasings are simple to include on the bed and offer powerful allergy protection. To add to the convenience, allergy encasings only need to be washed once a year or when soiled and these fabric encasings can easily be machine washed and dried.

Allergy bed encasings offer one of the most effective steps for allergy relief and a healthier night’s sleep. Understanding the aspects of allergy encasings can help you make an informed choice as to the encasing selection that is right for you.

For 25 years, Allergy Control Products has been recommended by thousands of physicians as the most trusted allergy company for revolutionary products. Whether you’re looking for the highest quality air purifier, air cleaner, air filters, hypoallergenic bedding or more.

Read more...

Seven Reasons to Choose Yoga For a Better Body and a Calmer Mind

Yoga has been around for centuries. Embraced equally by film stars, rock stars, high powered CEOs and New Age gurus, yoga’s stress-relieving, strength-building, low impact poses appeal to a wide range of individuals and body shapes. Even beginners can see and feel a difference after just a few short weeks of practice. All arguments aside, yoga works. So why haven’t you tried it? Here are seven really good reasons why you should:

7.) Symptom Relief - Several scientific studies have proven that yoga practice can greatly reduce the frequency and duration of asthma attacks, as well as the amount of medication needed to control or prevent attacks. Yogic breathing, pranayama , helps to strengthen the lungs and build breath control while back-bending poses open the chest and help increase air flow. Carpal tunnel syndrome can be alleviated with certain yoga poses. The lengthening and strengthening of the tendons offered in many yoga poses aids in relieving the pain, and in restoring the grip. The slow, low-impact nature of yoga exercise lends itself perfectly to arthritis sufferers. Joint pain and swelling can be reduced from the gentle exercise and from the stress relief granted tight, tensed muscles. The stress relieving nature of yoga has been shown to reduce the severity and frequency of headaches for migraine sufferers, as well.

6.) Disease Prevention – The stress relief offered through yoga practice can reduce the risk of heart disease, the number one killer of women in the US and Canada. Of further interest to women is yoga’s ability to strengthen and build bone density, preventing osteoporosis. It’s believed that yoga may reduce cortisol, and thereby aid in keeping calcium in your bones. The meditative nature of yoga can help raise levels of GABA in the brain, preventing the onset of Alzheimer’s disease. Lastly, yoga has been known to stimulate the pancreas in its production of insulin, lowering blood sugar levels and helping in the treatment of Type II diabetes.

5.) Good Form of Exercise – Not all forms of exercise are good for all of you. Yoga is low-impact, providing a safer way to stretch and strengthen. Yoga is non-competitive, allowing you a stress-free, introspective work-out. Yoga can be practiced indoors or out, so that it fits in with all climates and lifestyles. Beneficial yoga practice can be completed in as little as 10 minutes a day, making it the ideal exercise routine for today’s busy, on-the-go world. Yoga builds balanced muscle tone, strengthens the body’s core, and improves dexterity, hand-eye coordination and reaction time. It has also been clinically proven to increase joint range of motion and flexibility.

4.) Improved Body Chemistry – Yoga can have drastically good effects on your body’s inner workings. The increase in movement and blood flow offered in yoga practice can lower cholesterol and triglycerides in the blood stream. It is believed that yoga actually increases the amount of red blood cells in your blood, providing better oxygenation of the body, as well as increasing energy and reducing the risks of anemia. The lymphatic and endocrine systems also get a boost from yoga. The lymphatic system boosts immunity and raises your body’s disease fighting ability, while the endocrine system regulates hormones, and through yoga, both systems help increase the overall health and balance of your body.

3.) The Inner You – Much has been made of yoga’s effects on the psychological and emotional health of its practitioners. Yoga reduces stress through its slow movements and controlled breathing. It elevates and regulates your mood with its mind-body consciousness, its ability to improve your health overall, and its introspective nature. The attention required in yoga causes one to focus inwardly, reducing stress and anxiety, building a sense of calmness, alertness and even improving your memory.

2.) The Overall Inner You – Let’s recap a bit here. Yoga reduces stress, which lowers blood pressure. It stimulates your endocrine system, balancing hormone levels and lowering blood sugar. It helps increase the overall functioning and health of your circulatory and respiratory system. It lowers your heart rate. It raises your tolerance to pain. It relives certain chronic problems. It improves brain chemistry. Your internal organs receive a “yoga massage,” improving their functioning and disease fighting abilities. Your gastrointestinal health improves. Overall, there isn’t a body system not impacted positively by regular yoga practice.

1.) The Outer You – After examining all the things that yoga can do for the inside of you, let’s see what yoga can do for you that you can actually see. Yoga can reduce the signs of aging through its detoxification of the body. Increased blood flow and oxygenation can also improve skin tone and color. Yoga helps to induce better sleep, improving overall health, awareness and skin and muscle tone. Yoga poses build strength, lengthen muscles and get the body moving, all of which cause a reduction in weight, prevent cellulite from forming and improve posture. Lastly, yoga can boost your energy, and not just your everyday, running hither and thither and yon type energy. Yoga has been proven to improve your energy and performance in the bedroom, as well. You look better, you feel better, your body is more in tune with itself and you with it - all of which leads to an increased confidence that can’t be kept all to yourself.

Yoga may not be the cure of all ills, but it certainly can improve many. It’s an overall workout – inside as well as outside – that shows in your face, your eyes, the way you stand, the way you move, the way you live. What are you waiting for? Give yoga a try today!

Yandara.com offers yoga certification emphasizing yoga practice, teaching skills, organizing a class, creating confidence and making postural corrections. Visit us online to learn Hatha Yoga with Iyengar-based precision alignment, emphasizing heart-felt energy.

Read more...

Romantic Ideas for Valentine's Day and History

History:

February has long been a month of romance. February month connected with Valentine's Day merriment. We have, time and again, heard the name St. Valentine being uttered before us in this season of love. But just who is this St. Valentine? Why is this month associated with love and romance?. The origin of this lovers day goes back as early as 270 A.D and ongoing with the clash connecting a kindly priest and a mighty leader.

Some say the day is named after a bishop named Valentine, who was stationed in the Roman kingdom. Claudius II was the Emperor at that time. He thought that bachelor men made better soldiers, so he determined to make it a law that young men could not get married. Around 270 A.D., Valentine took pity on the ostracized soldiers who were not permitted to get married or see their sweetheart. Other stories suggest that Valentine may have been killed for attempting to help Christians escape harsh Roman prisons where they were often beaten and tortured.

A different story of the history of Valentines Day tells that Valentine fell in love with his jailer’s daughter. at this moment before his death, he sent her a note and signed it “from your Valentine.” An aura of romance bounded his finish and those who knew about it spread the tale. Bishop Valentine became Saint Valentine with his fame extending to England and France.

After his death, Valentine then became what is known as a “Patron Saint.” Some measured him the saintly overseer of an yearly festival in which young Romans would share out cards of friendliness to those they wished to formally see. This festival was held each 14 February.

Romantic Ideas for Valentine's Day:

One of the most popular ways couples celebrate 14 Feb Valentine's Day is by preparation a romantic getaway. Whether their romantic escape occurs accurately on Vzalentine's Day, the weekend before or after, anytime in the month of February the little extras that resorts add make getaways that much sweeter. Hotel Reservation India booking.

Other Some Romantic Ideas for Valentine's Day are following- Write a love letter or poem , Creatively use free flower petals, Surprise your significant other at times you usually do not see him or her, Cook a favorite meal at home, India Tour Packages.

Culture Holidays largest company of Tour & travel provides Vacation in India, cheap Air tickets, India Travel Package and also provide information about Cheap India Travel Packages, Car rental India.

Read more...

Sleep Disorder Tips

Are you having trouble falling asleep at night? Most people that get to sleep at night usually have things in common. One of those things is being able to relax after a long day at work. This article will discuss the most common mistakes people make when they can't fall asleep. 1. They don't take the time for themselves to unwind at night. If your day is filled with work and other responsibilities with very little time for yourself, then you're not alone. There has to be time for you. Not just five or ten minutes. You need to make a conscious effort to set the last hour of your day for yourself. You should use this time for anything you want to do. For more details www.activities-little-fingers.com Choose relaxing activities, such as reading or listening to music. While you should schedule this time everyday, the time doesn't necessarily have to be constructive or productive. Make sure you are not using the time for working. You probably do enough of that during the day. 2. They don't talk to their spouses in the evening. Most people don't know that they have their best support system right in their own home. All you have to do is start talking to your spouse. Talking about your day and the challenges you encounter is very therapeutic and may help you start relax in a night. May also find you are reconnecting with your spouse and that's good thing. Make sure when you're talking in the evening. You keep the conversation away from money and family finances. This will help you avoid confrontation before going to bed. 3. They don't acknowledge or prepare for challenges of the day ahead. Let's face it, if you have to work to support a family, then you are faced with many challenges during your workday. This can range from your projects or your office politics. Anyway it can lead to stress, anxiety and sleepless nights. Sit down with a pen and paper and make a list of what you have to do for the next day. One thing this exercise does is release stress and also helps you prepare for the day ahead. While you're writing you should start feeling relief and hopefully be relaxed enough to get to sleep. After reading this article, you learned about some common mistakes that people make when trying to fall asleep at night and how you can avoid them. For more details www.tips-getting-healthy.com Once you correct these mistakes, you should be on the right path to getting some sleep at night again. Disclaimer: This article is for informational purposes only and reflects an opinion. This article is not a substitute for medical advice. You should consult a physician for medical advisement.

Read more...