Immune Sensitization to the 60 kD Heat Shock Protein and Pregnancy Outcome

Heat shock proteins are highly conserved proteins present in organisms ranging from bacteria to man. They are both dominant microbial immunogens and among the first proteins produced during mammalian embryo development. Since bacterial and human heat shock proteins share a high degree of amino acid sequence homology, it has been suggested that sensitization to bacterial heat shock proteins during an infection may result in autoimmunity to human heat shock proteins. Infertile couples seeking in vitro fertilization (IVF) may have been previously sensitized to bacterial heat shock proteins as a consequence of an asymptomatic upper genital tract infection. Due to daily clinical monitoring and precisely timed fertilization these patients are an ideal study group to investigate the effect of prior sensitization to heat shock proteins on preimplantation embryo development and implantation failure. Immune sensitization at the level of the cervix to the 60 kD heat shock protein (hsp60) has been associated with implantation failure in some IVF patients. Similarly, the highest prevalence of circulating hsp60 antibodies among IVF patients was found in the sera of women whose embryos failed to develop in vitro. To more directly assess whether humoral immunity to hsp60 influenced in vitro embryo development, a mouse embryo culture model was established. Monoclonal antibody to mammalian hsp60 markedly impaired mouse embryo development in vitro. These data suggest that immune sensitization to human hsp60, possibly developed as a consequence of infection, may adversely affect pregnancy outcome in some patients

Heat shock protein expression during gametogenesis and embryogenesis.

When cells are subjected to various stress factors, they increase the production of a group of proteins called heat shock proteins (hsp). Heat shock proteins are highly conserved proteins present in organisms ranging from bacteria to man. Heat shock proteins enable cells to survive adverse environmental conditions by preventing protein denaturation. Thus the physiological and pathological potential of hsps is enormous and has been studied widely over the past two decades. The presence or absence of hsps influences almost every aspect of reproduction. They are among the first proteins produced during mammalian embryo development. In this report, the production of hsps in gametogenesis and early embryo development is described. It has been suggested that prolonged and asymptomatic infections trigger immunity to microbial hsp epitopes that are also expressed in man. This may be relevant for human reproduction, since many couples with fertility problems have had a previous genital tract infection. Antibodies to bacterial and human hsps are present at high titers in sera of many patients undergoing in vitro fertilization. In a mouse embryo culture model, these antibodies impaired the mouse embryo development at unique developmental stages. The gross morphology of these embryos resembled cells undergoing apoptosis. The TUNEL (terminal deoxynucleotidyl transferase-mediated X-dUTP nick end labeling) staining pattern, which is a common marker of apoptosis, revealed that embryos cultured in the presence of hsp antibodies stained TUNEL-positive more often than unexposed embryos. These data extend preexisting findings showing the detrimental effect of immune sensitization to hsps on embryo development

Transcriptome Profiling of Testis during Sexual Maturation Stages in Eriocheir sinensis Using Illumina Sequencing

The testis is a highly specialized tissue that plays dual roles in ensuring fertility by producing spermatozoa and hormones. Spermatogenesis is a complex process, resulting in the production of mature sperm from primordial germ cells. Significant structural and biochemical changes take place in the seminiferous epithelium of the adult testis during spermatogenesis. The gene expression pattern of testis in Chinese mitten crab (Eriocheir sinensis) has not been extensively studied, and limited genetic research has been performed on this species. The advent of high-throughput sequencing technologies enables the generation of genomic resources within a short period of time and at minimal cost. In the present study, we performed de novo transcriptome sequencing to produce a comprehensive transcript dataset for testis of E. sinensis. In two runs, we produced 25,698,778 sequencing reads corresponding with 2.31 Gb total nucleotides. These reads were assembled into 342,753 contigs or 141,861 scaffold sequences, which identified 96,311 unigenes. Based on similarity searches with known proteins, 39,995 unigenes were annotated based on having a Blast hit in the non-redundant database or ESTscan results with a cut-off E-value above 10−5. This is the first report of a mitten crab transcriptome using high-throughput sequencing technology, and all these testes transcripts can help us understand the molecular mechanisms involved in spermatogenesis and testis maturation

Role of Secreted Conjunctival Mucosal Cytokine and Chemokine Proteins in Different Stages of Trachomatous Disease

Trachoma, a disease of antiquity dating back to the 16th century B.C.E., predominates among developing countries, where it remains the primary cause of preventable blindness worldwide. In trachoma, recurrent Chlamydia trachomatis bacterial infections during childhood are thought to result in inflammation and subsequent conjunctival scarring that can progress to trichiasis (TT; chronic trachoma; inversion of ≥1 eyelash that touches the globe of the eye). The trachomatous follicular grade (TF; active disease) is a self-limiting disease, suggesting the coexistence of protective inflammatory proteins. The trachomatous inflammatory grade (TI; active disease) is more likely to progress to trachomatous scarring (TS; chronic trachoma). To date, there are only a handful of studies that have examined the immune response in trachoma, and these were primarily based on gene expression. Characterizing quantified conjunctival mucosal immune differences for secreted proteins among individuals with no, active, and chronic trachoma may identify protein biomarkers associated with protection versus disease, which would greatly aid our understanding of the immunopathogenesis of trachoma. In this study, we characterized 25 cytokine and chemokine proteins for all trachoma grades. We identified eight cytokines and chemokines as risk factors for chronic trachoma and four as protective. Together, these findings further characterize the immunopathologic responses involved during trachoma, which will likely aid in the design of a vaccine and immunomodulating therapeutics for trachoma

Band structures extending to very high spin in Xe126

High-spin states in Xe126 have been populated in the Se82(Ca48,4n)Xe126 reaction in two experiments, one at the VIVITRON accelerator in Strasbourg using the Euroball detector array, and a subsequent one with ATLAS at Argonne using the Gammasphere Ge-detector array. Levels and assignments made previously for Xe126 up to I=20 have been confirmed and extended. Four regular bands extending to a spin of almost I=60, which are interpreted as two pairs of signature partners with opposite parity, are identified for the first time. The α = 0 partner of each pair is connected to the lower-lying levels, whereas the two α = 1 partners remain floating. A fractional Doppler shift analysis of transitions in the strongest populated (Ï€,α)=(-,0) band provides a value of 5.20.50.4 b for the transition quadrupole moment, which can be related to a minimum in the potential-energy surface calculated by the ULTIMATE CRANKER cranked shell-model code at Îμâ‰0.35 and Îâ‰5°. The four lowest bands calculated for this minimum compare well with the two signature pairs experimentally observed over a wide spin range. A sharp upbend at â.,ω~1170 keV is interpreted as a crossing with a band involving the j15/2 neutron orbital, for which pairing correlations are expected to be totally quenched. The four long bands extend to within â5 spin units of a crossing with an yrast line defined by calculated hyperdeformed transitions and will serve as important stepping stones into the spin region beyond 60ħ for future experiments

Trends and transitions in the institutional environment for public and private science

The last quarter-century bore witness to a sea change in academic involvement with commerce. Widespread university-based efforts to identify, manage, and market intellectual property (IP) have accompanied broad shifts in the relationship between academic and proprietary approaches to the dissemination and use of science and engineering research. Such transformations are indicators of institutional changes at work in the environment faced by universities. This paper draws upon a fifteen-year panel (1981–1995) of university-level data for 87 research-intensive US campuses in order to document trends and transitions in relationships among multiple indicators of academic and commercial engagement. The institutional environment for public and private science is volatile, shifting in fits and starts from a situation conducive to organizational learning through high volume patenting to a more challenging arrangement that links indiscriminate pursuit of IP with declines in both the volume and impact of academic science. The pattern and timing of these transitions may support an enduring system of stratification that offers increasing returns to first-movers while limiting the opportunities available to universities that are later entrants to the commercial realm. Unpacking the systematic effects of university research commercialization requires focused attention on the sources and trajectories of profound institutional change.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42839/1/10734_2004_Article_2916.pd

Xenopus ADAM19 is involved in neural, neural crest and muscle development

ADAM19 is a member of the meltrin subfamily of ADAM metalloproteases. In Xenopus, ADAM19 is present as a maternal transcript. Zygotic expression starts during gastrulation and is apparent in the dorsal blastopore lip. ADAM19 expression through neurulation and tailbud formation becomes enriched in dorsal structures such as the neural tube, the notochord and the somites. Using morpholino knock-down, we show that a reduction of ADAM19 protein in gastrula stage embryos results in a decrease of Brachyury expression in the notochord concomitant with an increase in the dorsal markers, Goosecoid and Chordin. These changes in gene expression are accompanied by a decrease in phosphorylated AKT, a downstream target of the EGF signaling pathway, and occur while the blastopore closes at the same rate as the control embryos. During neurulation and tailbud formation, ADAM19 knock-down induces a reduction of the neural markers N-tubulin and NRP1 but not Sox2. In the somitic mesoderm, the expression of MLC is also decreased while MyoD is not. ADAM19 knockdown also reduces neural crest markers prior to cell migration. Neural crest induction is also decreased in embryos treated with an EGF receptor inhibitor suggesting that this pathway is necessary for neural crest cell induction. Using targeted knock-down of ADAM19 we show that the reduction of neural and neural crest markers is cell autonomous and that the migration if the cranial neural crest is perturbed. We further show that ADAM19 protein reduction affects somite organization, reduces 12-101 expression and perturbs fibronectin localization at the intersomitic boundary

Profile inversion of principal diffusivities through the use of a spatially modulated heating and a Fourier analysis

The through-thickness thermal diffusivity can be evaluated by the classical flash method. If an homogeneous and extended source is used to irradiate the surface and a thermographic camera is used to monitor the temperature evolution of the opposite side, a map of the through-thickness thermal diffusivity can be obtained in a single experiment and without any contact with the sample under inspection. In order to measure the in-plane thermal diffusivity of a plate-like sample or in one of the principal directions of its plane, a thermal gradient across the plane of the material has to be settled. The ratio of the Fourier transform of temperature at two different spatial frequencies is an exponential function of time multiplied by the diffusivity in the considered principal direction. This can be used to evaluate the diffusivity in an homogenous material. In order to maximise the signal-to-noise ratio, it is better if heat is absorbed over a series of periodic parallel strips (grid flash method). When the material presents a transverse gradient of conductivity, we propose, as a first approach, to perform the Fourier analysis over a sliding window corresponding to one period of the grid pattern. This method allowed us to quantify insitu the diffusivity decrease in a tensile composite sample due to the stress-induced density increase of transverse microcracks. We finally analysed a more rigorous method for transverse conductivity profile inversion. It is based on a perturbation method. The analytical expression of the "transfer function" between the Fourier transform of the temperature contrast and the Fourier transform of conductivity was established. We validated the proposed inverse technique on simulated and noise-corrupted thermograms. The approach is robust and the simulated profiles are very well resolved