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introduction of BRSV NS1 and NS2 into rabies virus also evoked resistance to interferon In distinct contrast to wild-type BRSVs, recombinant BRSVs (rBRSVs) without the NS proteins, and those lacking NS2 in particular, are strong inducers of IFN-a/b in bovine nasal broblasts and bronchoalveolar macrophages In addition, although the NS deletion mutants grew to wild-type rBRSV levels in cells lacking a functional IFN-a/b system, their replication was severely inhibited in IFNcompetent cells98 These results suggested that the NS proteins block induction of IFN-a/b gene expression Wild-type human respiratory syncytial virus (HRSV) is a poor inducer of a/b interferons (IFN-a/b) In accord with the results seen with BRSV, recombinant HRSV lacking the NS1 and NS2 genes was able to induce high levels of IFN-a and IFN-b in epithelial cells and macrophages99 The two proteins can function independently or coordinately.

Figure 20.3 The arrow follows the ovarian follicles (time course) from their maturation from primary follicles to the corpus luteum. (Adapted from Web site of Dr. Steven Scadding and Dr. Sandra K. Ackerley, http://www.uoguelph.ca/zoology/devobio/210labs/ovary4.html.)

where C4 j is the (normalized) fourth-order cumulant of the random process 4 2 2 dX j; given by C4 j EdX j; k 3 EdX j; k 2 = EdX j; k 2. From Eq. (2.25) it can be seen that the term log2 e 1 C4 j =2 =nj plays the role of g j from the Gaussian case and, up to the C4 j term, has the same form. Performing the regression of yj E log2 mj on j, we obtain, using nj 2 j n and under ID1, E^ E a

wj log2 mj 9 a log2 e 1 C4 j =2 wj 2j =n;

22 24

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Alphaviruses including Venezuelan (VEEV), eastern (EEEV), and western equine encephalitis viruses (WEEV) are potential agents of biological warfare and terrorism and important, naturally emerging zoonotic viruses A representative virus of this group is Sindbis virus, which possesses a nonstructural protein nsP2 that is a signi cant regulator of Sindbis virus host cell interactions This protein not only is a component of the replicative enzyme complex required for replication and transcription of viral RNAs but also plays a role in suppressing the antiviral response in Sindbis virus-infected cells nsP2 may act by decreasing interferon (IFN) production100,101 In another study, White and co-workers102 found that a single change (G to A) at nucleotide 3 of the 50 untranslated region (UTR) of the Venezuelan equine encephalitis virus (VEEV) V3000 virulent strain genome resulted in a virus that was avirulent in mice.

2:28

Figure 20.4 Women s menstrual cycle. (Courtesy of Women s Health Interactive, http://www. womens-health.com/health center/gynecology/gyn repro menstrual.html.)

which (1) shows that the estimate is asymptotically unbiased irrespective of the Gaussian hypothesis and (2) allows us to subtract a rst-order approximation of that bias. Similarly, Var log2 mj 9 2 log2 e 2 1 C4 j =2 ; nj 2:29

This mutant showed no growth disadvantage compared to the wild-type virus in cells derived from IFN-a/bR( / )mice Induction of IFN-a/b was the same for avirulent and virulent viruses; however, the avirulent mutant virus was more sensitive than the virulent strain to the antiviral actions of IFN-a/b Thus, increased sensitivity to IFN-a/b must play a major role in the in vivo attenuation Virus zoonoses causing hemorrhagic fevers include the Bunyaviridae Thomas et al103 found that bunyaviruses activate PKR but are only marginally sensitive to its antiviral effect In addition, NSs appeared to be different from other IFN antagonists, since it inhibited dsRNA-dependent IFN induction but had no effect on the dsRNA-activated PKR and RNase L systems Bunyamwera virus, of the family Bunyaviridae, possesses a nonstructural protein NSs that is a virulence factor that inhibits IFN-b gene expression in the mammalian host.

Xenobiotics can adversely affect the normal functions of the cells/organs of the reproductive system. These agents may induce a variety of outcomes, including prevention of ovulation and impairment of ovum transport, fertilization, or implantation. Endocrine disruptors may mimic endogenous hormones as well as directly destroy cellular components, leading to cell death. More indirect effects may include inhibition of key enzymes involved in steroid synthesis.

which again shows the similarity of form with the corresponding Gaussian case, Eq. (2.26), in the asymptotic limit. It follows that ^ Var a

Compounds within this class of substances can inhibit hypothalamic pituitary ovarian axis function by inhibiting gonadotropin secretion. Subsequently ovulation and estrus is suppress leading to infertility or reduced fertility.

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