Comprehensive Proteomic Analysis of Human Cervical−Vaginal Fluid

Dasari, Surendra; Pereira, Leonardo; Reddy, Ashok P.; Michaels, John-Edward A.; Lu, Xinfang; Jacob, Thomas; Thomas, Arthur W.; Rodland, Matthew; Roberts, Charles T.; Gravett, Michael G.; Nagalla, Srinivasa R.

doi:10.1021/pr0605419

Cited by 113 publications

(145 citation statements)

References 58 publications

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“…These data suggest that gonococcal Por may be able to bind more fH. This finding is likely to be biologically relevant because gonococci reside in the genital tract, an environment with a low concentration of fH (6). fH bound to Por F62 on Neisseria with sialylated LOS regulates the AP of complement more efficiently than fH bound to fHbp.…”

Section: Comparison Of Fh Binding To Meningococcal Fhbp and Gonococcamentioning

confidence: 82%

Functional Comparison of the Binding of Factor H Short Consensus Repeat 6 (SCR 6) to Factor H Binding Protein fromNeisseria meningitidisand the Binding of Factor H SCR 18 to 20 toNeisseria gonorrhoeaePorin

et al. 2009

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Both Neisseria meningitidis and Neisseria gonorrhoeae recruit the alternative pathway complement inhibitory protein factor H (fH) to their surfaces to evade complement-dependent killing. Meningococci bind fH via fH binding protein (fHbp), a surface-exposed lipoprotein that is subdivided into three variant families based on one classification scheme. Chimeric proteins that comprise contiguous domains of fH fused to murine Fc were used to localize the binding site for all three fHbp variants on fH to short consensus repeat 6 (SCR 6). As expected, fH-like protein 1 (FHL-1), which contains fH SCR 6, also bound to fHbp-expressing meningococci. Using site-directed mutagenesis, we identified histidine 337 and histidine 371 in SCR 6 as important for binding to fHbp. These findings may provide the molecular basis for recent observations that demonstrated human-specific fH binding to meningococci. Differences in the interactions of fHbp variants with SCR 6 were evident. Gonococci bind fH via their porin (Por) molecules (PorB.1A or PorB.1B); sialylation of lipooligosaccharide enhances fH binding. Both sialylated PorB.1B-and (unsialylated) PorB.1A-bearing gonococci bind fH through SCR 18 to 20; PorB.1A can also bind SCR 6, but only weakly, as evidenced by a low level of binding of FHL-1 relative to that of fH. Using isogenic strains expressing either meningococcal fHbp or gonococcal PorB.1B, we discovered that strains expressing gonococcal PorB.1B in the presence of sialylated lipooligosaccharide bound more fH, more effectively limited C3 deposition, and were more serum resistant than their isogenic counterparts expressing fHbp. Differences in fH binding to these two related pathogens may be important for modulating their individual responses to host immune attack.

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Section: Comparison Of Fh Binding To Meningococcal Fhbp and Gonococcamentioning

confidence: 82%

Functional Comparison of the Binding of Factor H Short Consensus Repeat 6 (SCR 6) to Factor H Binding Protein fromNeisseria meningitidisand the Binding of Factor H SCR 18 to 20 toNeisseria gonorrhoeaePorin

et al. 2009

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“…Moreover, DBP may be found not only in serum, but also in other biological fluids. The detection in cervicovaginal fluid (13), for example, has been taken to propose DBP as an indicator of up-regulated cell death and tissue remodeling accompanying labor (14).…”

Section: Vitamin Dmentioning

confidence: 99%

ENDOCRINOLOGY IN PREGNANCY: Bone metabolic changes during pregnancy: a period of vulnerability to osteoporosis and fracture

Sanz-Salvador

Garcı́a-Pérez

Tarı́n

et al. 2015

European Journal of Endocrinology

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Changes in bone density and bone markers suggest that pregnancy is associated with deterioration of bone mass in the mother. The metabolism of calcium resets to allow for the needs imposed by the building of the fetal skeleton. The fetus contributes to the process through the output of regulators from the placenta. Understanding of the whole process is limited, but some changes are unambiguous. There is an increase in the circulating levels of vitamin D, but its functional impact is unclear. Fetal parathyroid hormone (PTH) and PTH-related peptide (PTHrp) play an indirect role through support of a calcium gradient that creates hypercalcemia in the fetus. Placental GH, which increases up to the end of pregnancy, may exert some anabolic effects, either directly or through the regulation of the IGF1 production. Other key regulators of bone metabolism, such as estrogens or prolactin, are elevated during pregnancy, but their role is uncertain. An increase in the ratio of receptor activator of nuclear factor kappa B ligand (RANKL) to osteoprotegerin (OPG) acts as an additional pro-resorbing factor in bone. The increase in bone resorption may lead to osteoporosis and fragility fracture, which have been diagnosed, although rarely. However, the condition is transitory as long-term studies do not link the number of pregnancies with osteoporosis. Prevention is limited by the lack of identifiable risk factors. When fractures are diagnosed, rest, analgesics, or, when indicated, orthopedic intervention have demonstrated efficacy. Systemic treatment with anti-osteoporotic drugs is effective, but the potential harm to the fetus imposes caution in their use.

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“…Interestingly, monozygotic twins in cattle (generated by embryo splitting) were used as a model to eliminate genetic variability as a source for proteome differences. Indeed, proteomics approaches have identified biomarkers of uterine receptivity, such as the immunophilin FK506-binding protein 4, and reproductive tract dysfunction and disease in other species (Daikoku et al 2005, Dasari et al 2007.…”

Section: Proteomics and Metabolomicsmentioning

confidence: 99%

Genes involved in conceptus–endometrial interactions in ruminants: insights from reductionism and thoughts on holistic approaches

Spencer¹,

Sandra²,

Wolf³

2008

Reproduction

270

253

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This review summarizes new knowledge on expression of genes and provides insights into approaches for study of conceptus-endometrial interactions in ruminants with emphasis on the peri-implantation stage of pregnancy. Conceptus-endometrial interactions in ruminants are complex and involve carefully orchestrated temporal and spatial alterations in gene expression regulated by hormones from the ovary and conceptus. Progesterone is the hormone of pregnancy and acts on the uterus to stimulate blastocyst survival, growth, and development. Inadequate progesterone levels or a delayed rise in progesterone is associated with pregnancy loss. The mononuclear trophectoderm cells of the elongating blastocyst synthesize and secrete interferon-t (IFNT), the pregnancy recognition signal. Trophoblast giant binucleate cells begin to differentiate and produce hormones including chorionic somatomammotropin 1 (CSH1 or placental lactogen). A number of genes, induced or stimulated by progesterone, IFNT, and/or CSH1 in a cell-specific manner, are implicated in trophectoderm adhesion to the endometrial luminal epithelium and regulation of conceptus growth and differentiation. Transcriptional profiling experiments are beginning to unravel the complex dynamics of conceptus-endometrial interactions in cattle and sheep. Future experiments should incorporate physiological models of pregnancy loss and be complemented by metabolomic studies of uterine lumen contents to more completely define factors required for blastocyst survival, growth, and implantation. Both reduction and holistic approaches will be important to understand the multifactorial phenomenon of recurrent pregnancy loss and provide a basis for new strategies to improve pregnancy outcome and reproductive efficiency in cattle and other domestic animals.

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Comprehensive Proteomic Analysis of Human Cervical−Vaginal Fluid

Cited by 113 publications

References 58 publications

Functional Comparison of the Binding of Factor H Short Consensus Repeat 6 (SCR 6) to Factor H Binding Protein fromNeisseria meningitidisand the Binding of Factor H SCR 18 to 20 toNeisseria gonorrhoeaePorin

Functional Comparison of the Binding of Factor H Short Consensus Repeat 6 (SCR 6) to Factor H Binding Protein fromNeisseria meningitidisand the Binding of Factor H SCR 18 to 20 toNeisseria gonorrhoeaePorin

ENDOCRINOLOGY IN PREGNANCY: Bone metabolic changes during pregnancy: a period of vulnerability to osteoporosis and fracture

Genes involved in conceptus–endometrial interactions in ruminants: insights from reductionism and thoughts on holistic approaches

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