Antagonistic pleiotropy can maintain fitness variation in annual plants.

Antagonistic pleiotropy (AP) is a genetic trade-off between different fitness components. In annual plants, a trade-off between days to flower (DTF) and reproductive capacity often determines how many individuals survive to flower in a short growing season, and also influences the seed set of survivors. We develop a model of viability and fecundity selection informed by many experiments on the yellow monkeyflower, Mimulus guttatus, but applicable to many annual species. A viability/fecundity trade-off maintains stable polymorphism under surprisingly general conditions. We also introduce both spatial heterogeneity and temporal stochasticity in environmental parameters. Neither is necessary for polymorphism, but spatial heterogeneity allows polymorphism while also generating the often observed non-negative correlations in fitness components.

Advanced oxidation technology with photohydroionization as a surface treatment for controlling Listeria monocytogenes on stainless steel surfaces and ready-to-eat cheese and turkey.

Listeria monocytogenes is difficult to control in food and processing environments due to its widespread nature and ability to survive in a range of adverse conditions, including low temperatures, pH, and high salt concentrations. The objective of this study was to evaluate the efficacy of Photohydroionization™ (PHI; RGF Environmental Group, Inc., Riviera, Beach, FL), a novel advanced oxidation technology, as a surface treatment to control L. monocytogenes on food-contact surfaces, sliced American cheese, and ready-to-eat (RTE) turkey. A five-strain cocktail of L. monocytogenes was used to inoculate sample surfaces. Food-contact surfaces were exposed to ultraviolet and other oxidative gases produced by the PHI system for 10, 20, 30, 45, 60, and 120 s and 5, 10, and 15 min; cheese and turkey samples were treated for 30, 60, and 120 s and 5 min. For each matrix at each time point, seven samples were treated and enumerated by plating appropriate dilutions onto modified oxford medium and thin-agar-layer modified oxford medium. Results showed reductions (p<0.05) in L. monocytogenes: 4.37 log colony-forming units (CFU)/coupon on stainless steel after 15-min treatment. A 1.39 and 1.63 log CFU/sample after 120 s and 2.16 and 2.52 log CFU/sample after 5 min were seen on American cheese and ready-to-eat turkey, respectively. Lipid oxidation analyses performed on cheese and turkey samples indicated that PHI treatment did not affect (p>0.05) thiobarbituric acid-reactive substances values. This study demonstrates the efficacy of PHI treatment to reduce L. monocytogenes on stainless steel and RTE foods and may serve as a processing intervention to ensure safe production of food.

A Bayesian method for the joint estimation of outcrossing rate and inbreeding depression.

The population outcrossing rate (t) and adult inbreeding coefficient (F) are key parameters in mating system evolution. The magnitude of inbreeding depression as expressed in the field can be estimated given t and F via the method of Ritland (1990). For a given total sample size, the optimal design for the joint estimation of t and F requires sampling large numbers of families (100-400) with fewer offspring (1-4) per family. Unfortunately, the standard inference procedure (MLTR) yields significantly biased estimates for t and F when family sizes are small and maternal genotypes are unknown (a common occurrence when sampling natural populations). Here, we present a Bayesian method implemented in the program BORICE (Bayesian Outcrossing Rate and Inbreeding Coefficient Estimation) that effectively estimates t and F when family sizes are small and maternal genotype information is lacking. BORICE should enable wider use of the Ritland approach for field-based estimates of inbreeding depression. As proof of concept, we estimate t and F in a natural population of Mimulus guttatus. In addition, we describe how individual maternal inbreeding histories inferred by BORICE may prove useful in studies of inbreeding and its consequences.

Inhibition of thromboxane A2-induced arrhythmias and intracellular calcium changes in cardiac myocytes by blockade of the inositol trisphosphate pathway.

We have recently reported that left atrial injections of the thromboxane A(2) (TXA(2)) mimetic, (5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxy-1-octenyl]-2 -oxabicyclo[2.2.1]hept-5-yl]-5-heptenoic acid (U46619), induced ventricular arrhythmias in the anesthetized rabbit. Data from this study led us to hypothesize that TXA(2) may be inducing direct actions on the myocardium to induce these arrhythmias. The aim of this study was to further elucidate the mechanism responsible for these arrhythmias. We report that TXA(2)R is expressed at both the gene and protein levels in atrial and ventricular samples of adult rabbits. In addition, TXA(2)R mRNA was identified in single, isolated ventricular cardiac myocytes. Furthermore, treatment of isolated cardiac myocytes with U46619 increased intracellular calcium in a dose-dependent manner and these increases were blocked by the specific TXA(2)R antagonist, 7-(3-((2-((phenylamino)carbonyl)hydrazino)methyl)-7-oxabicyclo(2.2.1)hept-2-yl)-5-heptenoic acid (SQ29548). Pretreatment of myocytes with an inhibitor of inositol trisphosphate (IP(3)) formation, gentamicin, or with an inhibitor of IP(3) receptors, 2-aminoethoxydiphenylborate (2-APB), blocked the increase in intracellular calcium. In vivo pretreatment of anesthetized rabbits with either gentamicin or 2-APB subsequently inhibited the formation of ventricular arrhythmias elicited by U46619. These data support the hypothesis that TXA(2) can induce arrhythmias via a direct action on cardiac myocytes. Furthermore, these arrhythmogenic actions were blocked by inhibitors of the IP(3) pathway. In summary, this study provides novel evidence for direct TXA(2)-induced cardiac arrhythmias and provides a rationale for IP(3) as a potential target for the treatment of TXA(2)-mediated arrhythmias.

Inbreeding depression in an asexual population of Mimulus guttatus.

The reproductive mechanism, that is whether an organism outcrosses, selfs or asexually reproduces, has a substantial impact on the amount and pattern of genetic variation. In this study, we estimate genetic variation and genetic load for a predominately asexual population of Mimulus guttatus, and then compare our results to other studies of predominately sexually reproducing (outcrossing and selfing) populations of M. guttatus. The asexual population had low levels of heterozygosity (H(e) = 0.03) and low (but significantly non-zero) inbreeding load, especially when compared with other M. guttatus populations. This differs greatly from the sexual populations of Mimulus that display substantial inbreeding depression. We discuss a variety of reasons why we see such low load in this study and suggest future research projects to further explore the questions.

The genetic consequences of fluctuating inbreeding depression and the evolution of plant selfing rates.

The magnitude of inbreeding depression, a central parameter in the evolution of plant mating systems, can vary depending on environmental conditions. However, the underlying genetic mechanisms causing environmental fluctuations in inbreeding depression, and the consequences of this variation for the evolution of self-fertilization, have been little studied. Here, we consider temporal fluctuations of the selection coefficient in an explicit genetic model of inbreeding depression. We show that substantial variance in inbreeding depression can be generated at equilibrium by fluctuating selection, although the simulated variance tends to be lower than has been measured in experimental studies. Our simulations also reveal that purging of deleterious mutations does not depend on the variance in their selection coefficient. Finally, an evolutionary analysis shows that, in contrast to previous theoretical approaches, intermediate selfing rates are never evolutionarily stable when the variation in inbreeding depression is due to fluctuations in the selection coefficient on deleterious mutations.

Direct estimation of the mutation rate at dinucleotide microsatellite loci in Arabidopsis thaliana (Brassicaceae).

The mutation rate at 54 perfect (uninterrupted) dinucleotide microsatellite loci is estimated by direct genotyping of 96 Arabidopsis thaliana mutation accumulation lines. The estimated rate differs significantly among motif types with the highest rate for AT repeats (2.03 x 10(-3) per allele per generation), intermediate for CT (3.31 x 10(-4)), and lowest for CA (4.96 x 10(-5)). The average mutation rate per generation for this sample of loci is 8.87 x 10(-4) (s.e.=2.57 x 10(-4)). There is a strong effect of initial repeat number, particularly for AT repeats, with mutation rate increasing with the length of the microsatellite locus in the progenitor line. Controlling for motif and initial repeat number, chromosome 4 exhibited an elevated mutation rate relative to other chromosomes. The great majority of mutations were gains or losses of a single repeat. Generally, the data are consistent with the stepwise mutation model of microsatellite evolution. Several lines exhibited multiple step changes from the progenitor sequence, but it is unclear whether these are multi-step mutations or multiple single-step mutations. A survey of dinucleotide repeats across the entire Arabidopsis genome indicates that AT repeats are most abundant, followed by CT, and CA.

Evaluation of two thermal processing schedules at low relative humidity for elimination of Escherichia coli O157:H7 and Salmonella serovars in chopped and formed beef jerky.

Foodborne outbreaks have been linked to jerky produced under insufficient thermal processing schedules. Reduction of Escherichia coli O157:H7 and Salmonella serovars during thermal processing of chopped and formed beef jerky was evaluated under two processing schedules representative of those used by large-scale (LS) and small-scale (SS) jerky production facilities. Fresh chopped and formed all-beef jerky batter was inoculated with 5.8 to 7.3 log CFU of E. coli O157:H7 or Salmonella per g, extruded into strips, and thermally processed by LS or SS schedules. A >or=5.0-log CFU/g reduction of both pathogens occurred with <10% relative humidity and a cumulative process of 44 min at 55.6 degrees C followed by 46 min at 77.8 degrees C into the LS schedule. Additional drying at 77.8 degrees C for 3.5 h was needed to achieve a water activity of 0.67 and a moisture-to-protein ratio (MPR) of 0.77. For the SS process, a >or=5.0-log CFU/g reduction of both pathogens occurred with 15 to 20% relative humidity and a cumulative process of 45 min at 52 degrees C, 60 min at 57 degrees C, 45 min at 60 degrees C, 45 min at 63 degrees C, 90 min at 68 degrees C, and finishing with 30 min at 77 degrees C. After processing for an additional 90 min at 77 degrees C, water activity was 0.60 while the MPR was 0.82. The LS and SS processes for producing chopped and formed jerky provided >or=5.0 log lethality to control E. coli O157:H7 and Salmonella. However, both processes would require additional drying to achieve an MPR of 0.75 to be labeled as jerky.

Sanitizing in Dry-Processing Environments Using Isopropyl Alcohol Quaternary Ammonium Formula.

Dry-processing environments are particularly challenging to clean and sanitize because introduced water can favor growth and establishment of pathogenic microorganisms such as Salmonella. Our objective was to determine the efficacy of an isopropyl alcohol quaternary ammonium (IPAQuat) formula for eliminating potential Salmonella contamination on food contact surfaces. Clean stainless steel coupons and conveyor belt materials used in dry-processing environments were spot inoculated in the center of coupons (5 by 5 cm) with a six-serotype composite of Salmonella (approximately 10 log CFU/ml), subjected to IPAQuat sanitizer treatments with exposure times of 30 s, 1 min, or 5 min, and then swabbed for enumeration of posttreatment survivors. A subset of inoculated surfaces was soiled with a breadcrumb-flour blend and allowed to sit on the laboratory bench for a minimum of 16 h before sanitation. Pretreatment Salmonella populations (inoculated controls, 0 s treatment) were approximately 7.0 log CFU/25 cm(2), and posttreatment survivors were 1.31, 0.72, and < 0.7 (detection limit) log CFU/25 cm(2) after sanitizer exposure for 30 s, 1 min, or 5 min, respectively, for both clean (no added soil) and soiled surfaces. Treatment with the IPAQuat formula using 30-s sanitizer exposures resulted in 5.68-log reductions, whereas >6.0-log reductions were observed for sanitizer exposures of 1 and 5 min. Because water is not introduced into the processing environment with this approach, the IPAQuat formula could have sanitation applications in dry-processing environments to eliminate potential contamination from Salmonella on food contact surfaces.

A test of neutrality based on interlocus associations.

The evolutionary processes governing variability within genomic regions of low recombination have been the focus of many studies. Here, I investigate the statistical properties of a measure of interlocus genetic associations under the assumption that mutations are selectively neutral and sites are completely linked. This measure, denoted ZnS, is based on the squared correlation of allelic identity at pairs of polymorphic sites. Upper bounds for ZnS are determined by simulations. Various deviations from the neutral model, including several different forms of natural selection, will inflate the value of ZnS relative to its neutral theory expectations. Larger than expected values of ZnS are observed in genetic samples from the yellow-ac-scute and Adh regions of Drosophila melanogaster.

Speciation by reinforcement: a model derived from studies of Drosophila.

Reinforcement is an increase in premating reproductive isolation between taxa resulting from selection against hybrids. We present a model of reinforcement with a novel type of selection on female mating behavior. Previous models of reinforcement have focused on the divergence of female mating preferences between nascent species. We suggest that an increase in the level of female mating discrimination can yield reinforcement without further divergence of either male characters or female preferences. This model indicates that selection on mating discrimination is a viable mechanism for reinforcement and may allow speciation under less stringent conditions than selection on female preference. This model also incorporates empirical results from genetic studies of hybrid fitness determination in Drosophila species. We find that the details of inheritance, which include sex-linked transmission, sex-limited fertility reduction, and X-autosome epistasis, have important effects on the likelihood of reinforcement. In particular, X-autosome epistasis for hybrid fitness determination facilitates reinforcement when hybrid fertility reduction occurs in males, but hinders the process when it occurs in females. HALDANE's rule indicates that hybrid sterility will generally evolve in males prior to females within nascent species. Thus, HALDANE's rule and X-autosome epistasis provide conditions that are surprisingly favorable for reinforcement in Drosophila.

Deleterious mutations and genetic variation for flower size in Mimulus guttatus.

Mimulus guttatus is a wildflower that exhibits substantial genetic variation in flower size. Here, we test the hypothesis that this variation is caused by deleterious mutations maintained through mutation-selection balance. The deleterious-mutation model predicts that rare, partially recessive alleles will be the primary source of variation. We test this prediction by measuring the change in the mean flower size (deltaM) and the directional dominance of flower size (deltaB) within a selection experiment. If variation is due to rare (partially) recessive alleles, deltaB/deltaM is expected to be positive and exceed one. However, we obtain negative values for deltaB/deltaM from three independent selection lines. This result is statistically inconsistent with the deleterious-mutation model.

Polypoid prolapsing mucosal folds in diverticular disease.

Redundant or polypoid mucosal folds were found in eight surgically resected sigmoid colons with diverticular disease. Grossly, they were either swellings of mucosal folds or larger, leaflike, smooth-surfaced polyps with broad bases arising from mucosal folds. The number of lesions ranged from one to 11, and when multiple they formed two rows between diverticula. Swollen mucosal folds showed submucosal and mucosal vascular congestion, scanty thrombi, edema, hemorrhage, and hemosiderin deposition. Some were markedly inflamed. Polypoid lesions also showed crypt elongation and fission, upgrowth of muscle from the muscularis mucosae, and hyperplastic-metaplastic change typical of mucosal prolapse. One polyp showed evidence of an inverted diverticulum. Two cases displayed diffuse mucosal inflammation resembling inflammatory bowel disease in the region of the polyps. We speculate that these lesions result from a combination of venous congestion and mucosal redundancy secondary to spastic contraction of the muscle coat.

Idiopathic retractile (sclerosing) mesenteritis and its differential diagnosis.

We report a case of retractile mesenteritis presenting as an abdominal mass with incomplete small-bowel obstruction. Histological features included fat necrosis, fibrosis, elastosis, dystrophic calcification, and chronic inflammation. Lymphatic obstruction resulted in the accumulation of lipid-laden macrophages in the ileal mucosa. Ultrastructurally, myofibroblasts were the principal cells present. The differential diagnosis of retractile mesenteritis is discussed with particular attention to myofibroblastic disorders such as inflammatory pseudotumors, desmoids, retroperitoneal fibrosis, and other uncommon conditions that appear to be morphologically or clinically distinguishable although the etiology and pathogenesis are obscure.

Giant and symptomatic inflammatory polyps of the colon in idiopathic inflammatory bowel disease.

Four cases of giant inflammatory polyps were found in a series of 86 consecutive colectomies for inflammatory bowel disease. Two presented a distinctive clinical syndrome of abdominal pain and chronic iron-deficiency anemia due to blood loss. Secondary ulceration of the heads of the polyps accounted for the bleeding and anemia, and the size of the polyps accounted for the abdominal pain. In both cases unusually long portions of colon were involved by the giant polyps. The third and fourth cases had rare complications--reactivation of an enterocutaneous fistula and perforation of an acquired diverticulum. These cases demonstrate that giant inflammatory polyps may produce symptoms independently of the underlying inflammatory bowel disease. In reported cases of giant inflammatory polyps, approximately two-thirds had Crohn's disease and one-third had ulcerative colitis. The transverse colon was the commonest location, pain was the commonest symptom, and the polyps were localized to a short segment of colon in the majority of cases. More than 50% of cases mimicked neoplasm on barium enema. Giant inflammatory polyps may produce a variety of distinctive signs and symptoms and deserve independent recognition.

The local immunological defence system of the human endometrium.

The distribution of immunoglobulins and secretory component (SC) in the human endometrium has been studied by an immunoperoxidase technique. SC is present in a proportion of the epithelial cells and the amount of this substance is increased during the secretory phase of the cycle. A variety of immunoglobulins are present, in low concentrations, in the stromal interstitium during the secretory phase of the cycle and these are thought to diffuse passively from the plasma as a non-specific accompaniment of stomal oedema. Only IgA is found in the epithelial cells and this appears solely in those cells containing SC. No immunoglobuln-containing lymphoid cells are present in the endometrium. It is suggested that the endometrium lacks a true local secretory immune system but is able, because of its content of SC, to compensate for this by extracting polymeric IgA from the plasma. This system presumably helps to protect the endometrium against infection but the biological significance of its apparent control by progesterone is uncertain.

Fatal myxedema pericarditis in a Christian Scientist.

A case of fatal cardiac tamponade due to myxedema pericarditis is reported. The woman, a 54-year-old Christian Scientist, had never sought medical care and died at home. The pericardial sac occupied most of the thorax and contained 2,270 mL of fluid. A thick, shaggy, fibrinous exudate on the pericardium contained abundant cholesterol clefts typical of chronic effusion and myxedema. Thyroid function tests on postmortem blood revealed profound hypothyroidism, and the thyroid was atrophied, with the histologic appearance of primary atrophic thyroiditis. Pericardial effusion is common in myxedema, but cardiac tamponade is rare, only 13 cases being previously reported, none of which was fatal.

The histopathology of rectosigmoid biopsies from adults with bloody diarrhea due to verotoxin-producing Escherichia coli.

The histopathology of rectosigmoid biopsies from 20 patients with bloody diarrhea resulting from verotoxin-producing Escherichia coli infection is reported. The biopsies displayed a range of appearances, from normal to mild, nonspecific inflammation to acute infectious-type colitis. Surface-adherent or invasive bacteria were not identified. The morphologic features of infectious colitis and the absence of bacteria suggest that verotoxin may be responsible for the pathologic changes.

Fatal Aspergillus pneumonia in chronic granulomatous disease.

A 20-year-old man died from Aspergillus pneumonia three weeks after heavy exposure to grain dust. Lung biopsy and autopsy demonstrated a distinctive form of suppurating granulomatous bronchopneumonia caused by Aspergillus fumigatus, which was the sole agent cultured from the tissue. The liver and lymph nodes contained pigmented lipid histiocytes characteristic of chronic granulomatous disease, and subsequently both of the patient's brothers were found to have X-linked chronic granulomatous disease. The authors suggest that this morphologic expression of Aspergillus pneumonia should raise a suspicion of neutrophil dysfunction or chronic granulomatous disease.

The nucleotide sequence, structure, and preliminary studies on the transcriptional regulation of the bovine alpha skeletal actin gene.

The promoters of mammalian striated muscle actin gene contain binding sites for a number of transcription factors. Examples are the CArG boxes, which bind a protein identical to or related to serum response factor (SRF), E boxes, which bind myogenic determination factors such as MyoD and myogenin, and -CCGCCC- motifs, which bind the transcription factor Sp1. To date, the only mammalian sequences isolated and analyzed are from rodent and human. We have now isolated and sequenced the bovine gene encoding alpha skeletal actin, including almost 3 kb of 5'-flanking region. When compared to the human and rodent genes (the only ones previously cloned and for which 5'-flanking sequences to only approximately -750 are known), there was the expected conservation in the coding region. A comparison of the promoter regions indicated that the bovine gene has three CArG boxes in the 5'-flanking region in positions identical to those in other species. The bovine proximal promoter is unique from those of human and rodent in that it has only one E box in the vicinity of the TATA box, near -350, whereas the other mammals have three. Far upstream sequences reveal clusters of E boxes near -2,500 and -1,500. A minimal promoter element, to -297, which has no E boxes, is sufficient to activate transcription in myotubes derived from rat L6 and mouse C2C12 myoblasts.