Comparative vector competence of North American Lyme disease vectors.

Background: Understanding the drivers of Lyme disease incidence at broad spatial scales is critical for predicting and mitigating human disease risk. Previous studies have identified vector phenology and behavior, host community composition, and landscape features as drivers of variable Lyme disease risk. However, while the Lyme disease transmission cycles in the eastern and western USA involve different vector species (Ixodes scapularis and Ixodes pacificus, respectively), the role of vector-specific differences in transmission efficiency has not been directly examined.

Positive and Negative Regulation of Glycerol Utilization by the c-di-GMP Binding Protein PlzA in Borrelia burgdorferi.

, the causative agent of Lyme disease, encounters two disparate host environments during its enzootic life cycle, ticks and mammalian hosts. has a small genome that encodes a streamlined cyclic dimeric GMP (c-di-GMP) signaling system comprising a single diguanylate cyclase, Rrp1, and two phosphodiesterases. This system is essential for spirochete survival in ticks, in part because it controls the expression of the operon involved in glycerol utilization.

LtpA, a CdnL-type CarD regulator, is important for the enzootic cycle of the Lyme disease pathogen.

Little is known about how Borrelia burgdorferi, the Lyme disease pathogen, adapts and survives in the tick vector. We previously identified a bacterial CarD N-terminal-like (CdnL) protein, LtpA (BB0355), in B. burgdorferi that is preferably expressed at lower temperatures, which is a surrogate condition mimicking the tick portion of the enzootic cycle of B.

The oligopeptide ABC transporter OppA4 negatively regulates the virulence factor OspC production of the Lyme disease pathogen.

Borrelia burgdorferi sensu lato, the agent of Lyme disease, exists in nature through a complex enzootic life cycle that involves both ticks and mammals. The B. burgdorferi genome encodes five Oligopeptide ABC transporters (Opp) that are predicted to be involve in transport of various nutrients.

The sigma factor σ is required for the long-term survival of Leptospira biflexa in water.

Leptospira spp. comprise both pathogenic and free-living saprophytic species. Little is known about the environmental adaptation and survival mechanisms of Leptospira.

Identification of Acetylated Proteins in Borrelia burgdorferi.

Posttranslational modification (PTM) of proteins has emerged as a major regulatory mechanism in all three domains of life. One emerging PTM is Nε-lysine acetylation-the acetylation of the epsilon amino group of lysine residues. Nε-lysine acetylation is known to regulate multiple cellular processes.

Investigation of Expression Variation among Strains.

Outer surface protein C (OspC) is the most studied major virulence factor of , the causative agent of Lyme disease. The level of OspC varies dramatically among strains when cultured , but little is known about what causes such variation. It has been proposed that the difference in endogenous plasmid contents among strains contribute to variation in OspC phenotype, as contains more than 21 endogenous linear (lp) and circular plasmids (cp), and some of which are prone to be lost.

The EbpA-RpoN Regulatory Pathway of the Pathogen Leptospira interrogans Is Essential for Survival in the Environment.

Leptospira interrogans is the agent of leptospirosis, a reemerging zoonotic disease. It is transmitted to humans through environmental surface waters contaminated by the urine of mammals chronically infected by pathogenic strains able to survive in water for long periods. Little is known about the regulatory pathways underlying environmental sensing and host adaptation of L.

Insight into the Dual Functions of Bacterial Enhancer-Binding Protein Rrp2 of Borrelia burgdorferi.

Unlabelled: It is well established that the RpoN-RpoS sigma factor (σ(54)-σ(S)) cascade plays an essential role in differential gene expression during the enzootic cycle of Borrelia burgdorferi, the causative agent of Lyme disease. The RpoN-RpoS pathway is activated by the response regulator/σ(54)-dependent activator (also called bacterial enhancer-binding protein [bEBP]) Rrp2. One unique feature of Rrp2 is that this activator is essential for cell replication, whereas RpoN-RpoS is dispensable for bacterial growth.

[Spectrum-Effect Relationship of GualouXiebai Dropping Pills on Myocardial Ischemia].

Objective: To study the relationship between HPLC characteristic spectrum and pharmacodynamics on anti-myocardial ischemia of GualouXiebai dropping pills.

Methods: HPLC characteristic spectrum of GualouXiebai dropping pills was established, dropping pills were divided into five dose groups (3.75, 11.

Acetyl-Phosphate Is Not a Global Regulatory Bridge between Virulence and Central Metabolism in Borrelia burgdorferi.

In B. burgdorferi, the Rrp2-RpoN-RpoS signaling cascade is a distinctive system that coordinates the expression of virulence factors required for successful transition between its arthropod vector and mammalian hosts. Rrp2 (BB0763), an RpoN specific response regulator, is essential to activate this regulatory pathway.

Outer surface protein OspC is an antiphagocytic factor that protects Borrelia burgdorferi from phagocytosis by macrophages.

Outer surface protein C (OspC) is one of the major lipoproteins expressed on the surface of Borrelia burgdorferi during tick feeding and the early phase of mammalian infection. OspC is required for B. burgdorferi to establish infection in both immunocompetent and SCID mice and has been proposed to facilitate evasion of innate immune defenses.

[Study on HPLC Fingerprint of Trichosanthes Fruit and Its Processed Products].

Objective: To study the correlation on chemical fingerprint features between Trichosanthis Fructus and its processed products.

Methods: The chemical fingerprints were established by HPLC for the ethyl acetate extraction and the n-butanol extraction in Trichosanthis Fructus and its processed products,the common pattern was established by the mean and the median, and the similarity degree between Trichosanthis Fructus and its processed products was calculated by the correlation coefficient method and the included angle cosine method.

Results: There were 24 common peaks in the fingerprints of ethyl acetate extraction of Trichosanthis Fructus and its processed products,the average similarity degree was calculated separately by the correlation coefficient method and the included angle cosine method:the former as the value was 0.

Borrelia burgdorferi elongation factor EF-Tu is an immunogenic protein during Lyme borreliosis.

Borrelia burgdorferi, the etiological agent of Lyme disease, does not produce lipopolysaccharide but expresses a large number of lipoproteins on its cell surface. These outer membrane lipoproteins are highly immunogenic and have been used for serodiagnosis of Lyme disease. Recent studies have shown that highly conserved cytosolic proteins such as enolase and elongation factor Tu (EF-Tu) unexpectedly localized on the surface of bacteria including B.

Transferred interbacterial antagonism genes augment eukaryotic innate immune function.

Horizontal gene transfer allows organisms to rapidly acquire adaptive traits. Although documented instances of horizontal gene transfer from bacteria to eukaryotes remain rare, bacteria represent a rich source of new functions potentially available for co-option. One benefit that genes of bacterial origin could provide to eukaryotes is the capacity to produce antibacterials, which have evolved in prokaryotes as the result of eons of interbacterial competition.

Manganese and zinc regulate virulence determinants in Borrelia burgdorferi.

Borrelia burgdorferi, the causative agent of Lyme disease, must adapt to two diverse niches, an arthropod vector and a mammalian host. RpoS, an alternative sigma factor, plays a central role in spirochetal adaptation to the mammalian host by governing expression of many genes important for mammalian infection. B.

Human ABCC1 interacts and colocalizes with ATP synthase α, revealed by interactive proteomics analysis.

Human ABCC1 is a member of the ATP-binding cassette (ABC) transporter superfamily, and its overexpression has been shown to cause multidrug resistance by active efflux of a wide variety of anticancer drugs. ABCC1 has been shown to exist and possibly function as a homodimer. However, a possible heterocomplex involving ABCC1 has been indicated.

Role of fatty acid synthase in gemcitabine and radiation resistance of pancreatic cancers.

Human fatty acid synthase (FASN) is a homo-dimeric protein with multi-enzymatic activity responsible for the synthesis of palmitate. FASN expression has been found to be up-regulated in multiple types of human cancers and its expression correlates with poor prognosis possibly by causing treatment resistance. In this study, we tested if FASN expression is up-regulated in human pancreatic cancers and if its higher expression level in pancreatic cancers causes intrinsic resistance to gemcitabine and radiation.

Role of transmembrane segment 5 and extracellular loop 3 in the homodimerization of human ABCC1.

Resistance to multiple anticancer agents is a major obstacle in the successful treatment of cancers. Overexpression of some ATP-binding cassette (ABC) membrane transporters such as ABCC1 has been shown to be a major contributor of multidrug resistance (MDR) in both laboratory cell line models and the clinical setting. ABCC1 has been thought to function as a homodimer with a putative dimerization domain located in the first 281 amino acid residues, including MSD0 and L0 domains.

BAX insertion, oligomerization, and outer membrane permeabilization in brain mitochondria: role of permeability transition and SH-redox regulation.

BAX cooperates with truncated BID (tBID) and Ca(2+) in permeabilizing the outer mitochondrial membrane (OMM) and releasing mitochondrial apoptogenic proteins. The mechanisms of this cooperation are still unclear. Here we show that in isolated brain mitochondria, recombinant BAX readily self-integrates/oligomerizes in the OMM but produces only a minuscule release of cytochrome c, indicating that BAX insertion/oligomerization in the OMM does not always lead to massive OMM permeabilization.

A novel two mode-acting inhibitor of ABCG2-mediated multidrug transport and resistance in cancer chemotherapy.

Background: Multidrug resistance (MDR) is a major problem in successful treatment of cancers. Human ABCG2, a member of the ATP-binding cassette transporter superfamily, plays a key role in MDR and an important role in protecting cancer stem cells. Knockout of ABCG2 had no apparent adverse effect on the mice.

Role of eIF3a in regulating cell cycle progression.

Translational control is an essential process in regulation of gene expression, which occurs at the initiation step performed by a number of translation initiation factor complexes. eIF3a (eIF3 p170) is the largest subunit of the eIF3 complex. eIF3a has been suggested to play roles in regulating translation of a subset of mRNAs and in regulating cell cycle progression and cell proliferation.

Characterization and analyses of multidrug resistance-associated protein 1 (MRP1/ABCC1) polymorphisms in Chinese population.

Objective: To explore the distribution frequencies of four common single nucleotide polymorphisms (SNPs) of MRP1/ABCC1 in a mainland Chinese population and investigate whether these SNPs affect the expression and function of the MRP1/ABCC1.

Methods: The genotype of 208 healthy volunteers was determined using PCR-restriction fragment length polymorphism. The four candidated SNPs were recreated by site-directed mutagenesis and tested for their effect on MRP1/ABCC1 expression and multidrug resistance function in stable transfected HEK293 and CHO-K1 cell lines.

Effect of cysteine mutagenesis on the function and disulfide bond formation of human ABCG2.

ABCG2 is a member of the ATP-binding cassette (ABC) transporter superfamily. Its overexpression causes multidrug resistance in cancer chemotherapy. Based on its apparent half size in sequence when compared with other traditional ABC transporters, ABCG2 has been thought to exist and function as a homodimer linked by intermolecular disulfide bonds.

Role of eIF3a (eIF3 p170) in intestinal cell differentiation and its association with early development.

Eukaryotic initiation factor 3a (eIF3a) has been suggested to play a regulatory role in mRNA translation. Decreased eIF3a expression has been observed in differentiated cells while higher levels have been observed in cancer cells. However, whether eIF3a plays any role in differentiation and development is currently unknown.