Characterization of interleukin-1 beta 2, a novel interleukin-1 expressed by the early pig conceptus during establishment of pregnancy

It is essential that the early mammalian embryo attaches to the uterus or implants to survive. Most embryonic mortality is associated with complications during this process resulting in a loss of 25-60% of embryos or pregnancies. To promote implantation, the embryo will release proinflammatory cytokines. Interleukin-1 beta (IL-1B) is a proinflammatory cytokine released by the human, rodent and pig embryo that is believed to be important for implantation. The gene encoding IL-1B has duplicated in the pig resulting in two distinct genes; IL-1B1 and a novel gene referred to as interleukin-1 beta 2 (IL-1B2). It�s believed that IL-1B2, rather than IL-1B1, is released by the early pig embryo, however, the function of IL-1B2 is unknown. To better understand the involvement of proinflammatory cytokines during implantation, we characterized IL-1B2�s activity within the pig endometrium. Based on experiments presented in this dissertation we conclude that pig embryos release IL-1B2 as early as Day 6 of development, IL-1B2 increases the activity and production of proteins within the endometrium that may be necessary for implantation and within the endometrium, IL-1B2 may have less activity when compared with IL-1B1. Overall, the early pig embryo releases a newly discovered IL-1 that likely creates a balanced proinflammatory environment within the endometrium to enhance implantation. Investigations of embryo implantation, with a special emphasis on IL- 1 system, will increase our understanding of early pregnancy in humans and in animals used in production of food and biomedical research

Effect of RU486, a progesterone antagonist, on uterine progesterone receptor, embryonic development and ovarian function during early pregnancy in pigs

The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file.Title from PDF of title page (University of Missouri--Columbia, viewed on December 29, 2009).Thesis advisor: Dr. Matthew C. Lucy and Rodney D. Geisert.Vita.M.S. University of Missouri--Columbia 2009.Progesterone (P4) down-regulates the progesterone receptor (PGR) exclusively within the epithelium of the pig uterus near d 8 of the estrous cycle and pregnancy. How P4 down-regulates the PGR is not understood but is considered necessary for establishment of pregnancy. Progesterone is suggested to increase expression of a cytokine, RANKL, in the uterine epithelium that can activate nuclear factor-kappa B (NF-[kappa]B). Nuclear factor-kappa B is a transcription factor thought to block expression of the PGR, resulting in PGR down-regulation. To test this hypothesis, gilts were injected with a P4 antagonist, RU486, on d 3, 4 and 5 (T1) or on d 6 and d 7 (T2) of pregnancy. The uterus was removed on d 8 and d 12 and the endometrium measured for PGR and RANKL mRNA expression as well as activation of NF-[kappa]B within the uterine epithelium. Treatment of gilts with RU486 increased PGR mRNA expression, indicating that P4 does down-regulated the PGR. Expression of RANKL was greater in gilts injected with RU486 and activation of NF-[kappa]B was not different between treatments on d 8, indicating that RANKL and NF-[kappa]B may not be involved in PGR down-regulation. Activation of NF-[kappa]B did increase on d 12 in treatments that were conducive to normal conceptus development, possibly triggered by conceptus release of NF-kappa B (DNA-binding protein) release of interleukin-1 beta (IL-1[beta]).Includes bibliographical references

The Legal Status of Spyware

This Article examines the legal status of Spyware under federal and common law in the United States of America. The Authors begin with a technical overview of Spyware technology, which covers Spyware\u27s functionality, methods of dispersion, and classification. The Authors then analyze the treatment of Spyware under the Computer Fraud and Abuse Act, the Stored Communications Act, the Wiretap Act, and under general tort claims of trespass to chattels, invasion of privacy, and intrusion upon seclusion. The Authors conclude that none of the aformentioned causes of action provide an adequate remedy at law for Spyware victims. Moreover, the Authors note that even if an adequate cause of action were to exist, Spyware developers could avoid civil litigation by operating solely within Spyware friendly jurisdictions. The Authors speculate that an appropriate solution would be for the legislature to require all Spyware programs to contain multi-click End User License Agreements. Not only would this approach protect consumers by enabling them to make informed decisions and creating an effective cause of action against Spyware distributors, it would also help the Spyware industry as a whole by legitimizing commercially viable Spyware programs

Quit Smoking and Run For Your Life!

To The Editor: The World Health Organization promotes the World No Tobacco Day on May 31

The Legal Status of Spyware

This Article examines the legal status of Spyware under federal and common law in the United States of America. The Authors begin with a technical overview of Spyware technology, which covers Spyware\u27s functionality, methods of dispersion, and classification. The Authors then analyze the treatment of Spyware under the Computer Fraud and Abuse Act, the Stored Communications Act, the Wiretap Act, and under general tort claims of trespass to chattels, invasion of privacy, and intrusion upon seclusion. The Authors conclude that none of the aformentioned causes of action provide an adequate remedy at law for Spyware victims. Moreover, the Authors note that even if an adequate cause of action were to exist, Spyware developers could avoid civil litigation by operating solely within Spyware friendly jurisdictions. The Authors speculate that an appropriate solution would be for the legislature to require all Spyware programs to contain multi-click End User License Agreements. Not only would this approach protect consumers by enabling them to make informed decisions and creating an effective cause of action against Spyware distributors, it would also help the Spyware industry as a whole by legitimizing commercially viable Spyware programs

Advances in understanding large-scale responses of the water cycle to climate change

Globally, thermodynamics explains an increase in atmospheric water vapor with warming of around 7%/°C near to the surface. In contrast, global precipitation and evaporation are constrained by the Earth's energy balance to increase at ∼2–3%/°C. However, this rate of increase is suppressed by rapid atmospheric adjustments in response to greenhouse gases and absorbing aerosols that directly alter the atmospheric energy budget. Rapid adjustments to forcings, cooling effects from scattering aerosol, and observational uncertainty can explain why observed global precipitation responses are currently difficult to detect but are expected to emerge and accelerate as warming increases and aerosol forcing diminishes. Precipitation increases with warming are expected to be smaller over land than ocean due to limitations on moisture convergence, exacerbated by feedbacks and affected by rapid adjustments. Thermodynamic increases in atmospheric moisture fluxes amplify wet and dry events, driving an intensification of precipitation extremes. The rate of intensification can deviate from a simple thermodynamic response due to in‐storm and larger‐scale feedback processes, while changes in large‐scale dynamics and catchment characteristics further modulate the frequency of flooding in response to precipitation increases. Changes in atmospheric circulation in response to radiative forcing and evolving surface temperature patterns are capable of dominating water cycle changes in some regions. Moreover, the direct impact of human activities on the water cycle through water abstraction, irrigation, and land use change is already a significant component of regional water cycle change and is expected to further increase in importance as water demand grows with global population

Novel Bacterial Diversity and Fragmented eDNA Identified in Hyperbiofilm-Forming Pseudomonas aeruginosa Rugose Small Colony Variant

Pseudomonas aeruginosa biofilms represent a major threat to health care. Rugose small colony variants (RSCV) of P. aeruginosa, isolated from chronic infections, display hyperbiofilm phenotype. RSCV biofilms are highly resistant to antibiotics and host defenses. This work shows that RSCV biofilm aggregates consist of two distinct bacterial subpopulations that are uniquely organized displaying contrasting physiological characteristics. Compared with that of PAO1, the extracellular polymeric substance of RSCV PAO1ΔwspF biofilms presented unique ultrastructural characteristics. Unlike PAO1, PAO1ΔwspF released fragmented extracellular DNA (eDNA) from live cells. Fragmented eDNA, thus released, was responsible for resistance of PAO1ΔwspF biofilm to disruption by DNaseI. When added to PAO1, such fragmented eDNA enhanced biofilm formation. Disruption of PAO1ΔwspF biofilm was achieved by aurine tricarboxylic acid, an inhibitor of DNA-protein interaction. This work provides critical novel insights into the contrasting structural and functional characteristics of a hyperbiofilm-forming clinical bacterial variant relative to its own wild-type strain

LIM kinase inhibitors disrupt mitotic microtubule organization and impair tumor cell proliferation

The actin and microtubule cytoskeletons are critically important for cancer cell proliferation, and drugs that target microtubules are widely-used cancer therapies. However, their utility is compromised by toxicities due to dose and exposure. To overcome these issues, we characterized how inhibition of the actin and microtubule cytoskeleton regulatory LIM kinases could be used in drug combinations to increase efficacy. A previously-described LIMK inhibitor (LIMKi) induced dose-dependent microtubule alterations that resulted in significant mitotic defects, and increased the cytotoxic potency of microtubule polymerization inhibitors. By combining LIMKi with 366 compounds from the GSK Published Kinase Inhibitor Set, effective combinations were identified with kinase inhibitors including EGFR, p38 and Raf. These findings encouraged a drug discovery effort that led to development of CRT0105446 and CRT0105950, which potently block LIMK1 and LIMK2 activity in vitro, and inhibit cofilin phosphorylation and increase αTubulin acetylation in cells. CRT0105446 and CRT0105950 were screened against 656 cancer cell lines, and rhabdomyosarcoma, neuroblastoma and kidney cancer cells were identified as significantly sensitive to both LIMK inhibitors. These large-scale screens have identified effective LIMK inhibitor drug combinations and sensitive cancer types. In addition, the LIMK inhibitory compounds CRT0105446 and CRT0105950 will enable further development of LIMK-targeted cancer therapy