Ty1-copia-retrotransposon Behavior in a Polyploid Cotton

Retrotransposons constitute a ubiquitous and dynamic component of plant genomes. Intragenomic and intergenomic comparisons of related genomes offer potential insights into retrotransposon behavior and genomic effects. Here, we have used fluorescent in-situ hybridization to determine the chromosomal distributions of a Ty1-copia-like retrotransposon in the cotton AD-genome tetraploid Gossypium hirsutum and closely related putative A- and D-genome diploid ancestors. Retrotransposon clone A108 hybridized to all G. hirsutum chromosomes, approximately equal in intensity in the A- and D-subgenomes. Similar results were obtained by hybridization of A108 to the A-genome diploid G. arboreum, whereas no signal was detected on chromosomes of the D-genome diploid G. raimondii. The significance and potential causes of these observations are discussed.     

Autologous breast reconstruction: the Vanderbilt experience (1998 to 2005) of independent predictors of displeasing outcomes

BACKGROUND: Optimal surgical outcomes are dependent on an appreciation of comorbid conditions that may handicap results. The purpose of this retrospective analysis was to delineate risk factors for complications after autologous breast reconstruction. STUDY DESIGN: An institutional database was constructed of patients who underwent autologous breast reconstruction from 1998 to 2005. Variables captured included age, diabetes and smoking status, prereconstruction radiation therapy, concomitant breast resection, preoperative albumin, flap type, and body mass index (BMI; based on World Health Organization classifications: BMI>25, overweight; >30, obese). The primary outcome was noninfectious wound complications (NIWC), a novel classification based on the extent of tissue derangement and need for operative intervention. Secondary outcomes were wound infection, hematoma, hernia, and fat necrosis. Statistical analysis was performed using chi-square tests and multiple logistic regression. RESULTS: The analysis included 200 flaps (transverse rectus abdominis myocutaneous [TRAM]=171; latissimus dorsi=29) in 180 patients. There were 19 infections (9.5%), 3 total flap losses (1.5%), 14 hematomas (7%), and 11 donor-site hernias (6%). The incidences of fat necrosis and any NIWC were 18% and 36%, respectively. Mean followup was 13.1 months (range 1.1 to 51.7 months). Multiple logistic regression demonstrated that obesity (BMI>30) is a statistically significant independent risk factor for any NIWC (hazards ratio=6.58; 95% CI, 2.85 to 15.18; p < 0.01) and for NIWC requiring operative treatment (NIWC>or=3; hazard ratio=6.23; 95% CI 2.15 to 18.05; p < 0.01). Increased BMI predicts NIWC, NIWC requiring operative intervention, and wound infection (p < 0.01). CONCLUSIONS: These data suggest that obesity is a strong predictor of simple and complex NIWC and of wound infection after autologous breast reconstruction. Obese patients should be counseled about their significantly increased risk of experiencing these unwanted outcomes.     

Rocaglates as Antivirals: Comparing the Effects on Viral Resistance,Anti-Coronaviral Activity,RNA-Clamping on eIF4A and Immune Cell Toxicity

Rocaglates are potent broad-spectrum antiviral compounds with a promising safety profile. They inhibit viral protein synthesis for different RNA viruses by clamping the 5′-UTRs of mRNAs onto the surface of the RNA helicase eIF4A. Apart from the natural rocaglate silvestrol, synthetic rocaglates like zotatifin or CR-1-31-B have been developed. Here, we compared the effects of rocaglates on viral 5′-UTR-mediated reporter gene expression and binding to an eIF4A-polypurine complex. Furthermore, we analyzed the cytotoxicity of rocaglates on several human immune cells and compared their antiviral activities in coronavirus-infected cells. Finally, the potential for developing viral resistance was evaluated by passaging human coronavirus 229E (HCoV-229E) in the presence of increasing concentrations of rocaglates in MRC-5 cells. Importantly, no decrease in rocaglate-sensitivity was observed, suggesting that virus escape mutants are unlikely to emerge if the host factor eIF4A is targeted. In summary, all three rocaglates are promising antivirals with differences in cytotoxicity against human immune cells, RNA-clamping efficiency, and antiviral activity. In detail, zotatifin showed reduced RNA-clamping efficiency and antiviral activity compared to silvestrol and CR-1-31-B, but was less cytotoxic for immune cells. Our results underline the potential of rocaglates as broad-spectrum antivirals with no indications for the emergence of escape mutations in HCoV-229E.     

Isolated and combined deficiencies of NADH dehydrogenase (complex I) in muscle tissue of children with mitochondrial myopathies

We describe eight children with complex I deficiency, four of them with an isolated, the other four with an additional deficiency of complex IV. Clinical, chemical and morphological findings were compared from patients with isolated and combined deficiency. In both groups, the age of onset of symptoms was between the 1st day and the 4th month of life. Clinical and biochemical heterogeneity were observed. We found no correlation between residual activity of complex I in muscle, blood lactate level, and severity of clinical symptoms. Newborns presenting with severe lactic acidosis and children with later onset myopathy were seen in both groups. The group with combined complex I deficiency showed a more severe clinical course. By light microscopy ragged red fibres were only found in two patients with combined deficiency. However, by electron microscopy structural alterations of the mitochondria were observed in six out of seven muscle specimens.     

Treatment of hypercholesterolemia in children and adolescents

In patients with severe genetic hypercholesterolemia, therapeutic reduction of elevated serum total cholesterol and LDL cholesterol should begin in early childhood to lower the risks of cardiovascular disease later in life. We evaluated the effects of outpatient therapy with diet alone and with combined diet and drug therapy in children and adolescents with hypercholesterolemia of apparent dominant inheritance. Serum lipid values before and during dietary treatment were available in 35 patients (mean age at start of treatment 7.9 years, range 2.0-17.6 years) followed for an average duration of 17.5 months (range 4-70 months). A comparison between untreated state and combined therapy with diet and cholestyramine was possible in 14 patients (mean age 8.6 years, range 2.4-17.0 years) followed for 27.9 months (range 4-97 months). Dietary modification achieved by repeated counseling and training lowered serum total cholesterol by mean (+/- SE) 11.7 +/- 1.9% (p < 0.0001) and LDL cholesterol by 17.3 +/- 3.5% (p < 0.0001). However, five of 35 patients did not show an appreciable effect of therapy (cholesterol reduction < 5%), possibly because of non-compliance. Diet combined with cholestyramine in an average dose of 0.36 g/kg body weight/day reduced total cholesterol by 33.0 +/- 2.4% (p < 0.0001) and LDL cholesterol by 37.5 +/- 4.3% (p < 0.0001) and was effective in all patients. Both forms of treatment had no effect on serum triglycerides and HLD cholesterol. No serious side effects were noted, and percentile values for weight and height remained unchanged in all but three obese children.(ABSTRACT TRUNCATED AT 250 WORDS)