Partially local three-way alignments and the sequence signatures of mitochondrial genome rearrangements

Background

Genomic DNA frequently undergoes rearrangement of the gene order that can be localized by comparing the two DNA sequences. In mitochondrial genomes different mechanisms are likely at work, at least some of which involve the duplication of sequence around the location of the apparent breakpoints. We hypothesize that these different mechanisms of genome rearrangement leave distinctive sequence footprints. In order to study such effects it is important to locate the breakpoint positions with precision.

Results

We define a partially local sequence alignment problem that assumes that following a rearrangement of a sequence F, two fragments L, and R are produced that may exactly fit together to match F, leave a gap of deleted DNA between L and R, or overlap with each other. We show that this alignment problem can be solved by dynamic programming in cubic space and time. We apply the new method to evaluate rearrangements of animal mitogenomes and find that a surprisingly large fraction of these events involved local sequence duplications.

Conclusions

The partially local sequence alignment method is an effective way to investigate the mechanism of genomic rearrangement events. While applied here only to mitogenomes there is no reason why the method could not be used to also consider rearrangements in nuclear genomes.

     

Least median of squares and iteratively re‐weighted least squares as robust linear regression methods for fluorimetric determination of α‐lipoic acid in capsules in ideal and non‐ideal cases of linearity

This study outlines two robust regression approaches, namely least median of squares (LMS) and iteratively re‐weighted least squares (IRLS) to investigate their application in instrument analysis of nutraceuticals (that is, fluorescence quenching of merbromin reagent upon lipoic acid addition). These robust regression methods were used to calculate calibration data from the fluorescence quenching reaction (?F and F‐ratio) under ideal or non‐ideal linearity conditions. For each condition, data were treated using three regression fittings: Ordinary Least Squares (OLS), LMS and IRLS. Assessment of linearity, limits of detection (LOD) and quantitation (LOQ), accuracy and precision were carefully studied for each condition. LMS and IRLS regression line fittings showed significant improvement in correlation coefficients and all regression parameters for both methods and both conditions. In the ideal linearity condition, the intercept and slope changed insignificantly, but a dramatic change was observed for the non‐ideal condition and linearity intercept. Under both linearity conditions, LOD and LOQ values after the robust regression line fitting of data were lower than those obtained before data treatment. The results obtained after statistical treatment indicated that the linearity ranges for drug determination could be expanded to lower limits of quantitation by enhancing the regression equation parameters after data treatment. Analysis results for lipoic acid in capsules, using both fluorimetric methods, treated by parametric OLS and after treatment by robust LMS and IRLS were compared for both linearity conditions.     

Reproductive toxic impact of subchronic treatment with combined butylparaben and triclosan in weanling male rats

The effect of treatment with combined butylparaben and triclosan on male gonadal toxicity in weanling rats was investigated. All treated groups experienced atrophy in the ventral prostate and seminal vesicle, likewise significant depletion in the number and motility of sperm. Given individually or combined butylparaben and triclosan, significantly decreased testosterone, luteinizing hormone, and follicle‐stimulating hormone levels. Individual treatment with tested compounds caused significant elevation in the E₂ level, whereas combined treatment did not alter the E₂ level. Testicular DNA damage was recorded in all treated groups. Moreover, the testicular malondialdehyde level was significantly elevated, along with a significant decrease in catalase enzyme activity in all treated groups. Superoxide dismutase enzyme activity was significantly decreased in the butylparaben‐treated group, increased in the triclosan‐treated group, and nonsignificantly changed the butylparaben‐triclosan‐treated group. The combined treatment produced an endocrine disturbance with a concomitant induction of testicular oxidative stress, which may represent a common mechanism of endocrine disruptor‐mediated dysfunction.     

Prevalence of minor musculoskeletal anomalies in children with congenital hypothyroidism

In the last decade a high frequency of extrathyroidal congenital anomalies has been reported in infants with congenital hypothyroidism (CH) detected by neonatal screening. In the present study the occurrence of additional congenital malformations (CM) in a cohort of children with confirmed primary CH due to thyroid dysgenesis was investigated. A high prevalence of extrathyroidal major congenital anomalies (15.9%), more than 5-fold higher than that reported in the Egyptian population (2.7%), was found. The cardiac and musculoskeletal systems were the most commonly involved, comprising 9.09 and 47.72% of all anomalies, respectively. The high prevalence of musculoskeletal anomalies in this study was mostly due to minor anomalies as brachydactyly and digitalization of thumbs. The type of dysgenesis (i.e. aplastic, ectopic or hypoplastic) as well as the severity of hypothyroidism, as assessed by TSH and T(4) levels at diagnosis, had no relation with the occurrence of extrathyroidal abnormalities.     

Iron and zinc supplies mitigate cadmium toxicity in micropropagated banana (Musa spp.)

Plant Cell, Tissue and Organ Culture (PCTOC) - Cadmium (Cd) is a toxic heavy metal that negatively affects plant growth and physiology. Plants display multiple changes in physiological and...     

The role of tumor necrosis factor receptor superfamily member 4 (TNFRSF4) gene expression in diagnosis and prognosis of acute myeloid leukemia

Molecular Biology Reports - Acute myeloid leukemia (AML) is still challenging in predicting the prognosis due to its high heterogeneity. Molecular aberrations and abnormalities play a significant...     

Ameliorative effects of autophagy inducer,simvastatin on alcohol-induced liver disease in a rat model

Alcoholic liver disease (ALD) encompasses a variety of liver injuries with various underlying mechanisms but still no effective treatment. So we aimed to monitor the influence of simvastatin on alcohol-induced liver injury and elucidate the underlying mechanisms of its cytoprotective effect. Thirty male albino rats were randomly divided into five equal groups. Group 1 (control): received a standard diet; group 2: received simvastatin (10 mg kg⁻¹ day ⁻¹) once a day orally for 8 weeks; group 3: received 20% ethanol (7.9 g kg ⁻¹ day ⁻¹) daily orally for 8 weeks; group 4: received 20% ethanol along with same simvastatin dose daily for 8 weeks; group 5: received 20% ethanol orally for 8 weeks then received the same simvastatin dose for the next 8 weeks. Serum alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were measured. Liver tissue malondialdehyde, reduced glutathione levels, and superoxide dismutase activity were estimated. B-cell lymphoma 2 and C/EBP homologous protein levels were evaluated by enzyme linked immunosorbent assay (ELISA). Light chain 3-II and peroxisome proliferation-activated receptor gamma messenger RNA expression was assessed by real-time polymerase chain reaction. Immunohistochemical staining was performed using anti-rat tumor necrosis factor-alpha antibody. Our results revealed that simvastatin treatment was able to ameliorate alcohol-induced liver damage; the improved biochemical data were confirmed by histopathological evaluation. Simvastatin being an autophagy inducer was able to prevent and reverse alcohol-induced liver changes via induction of autophagy, attenuation of oxidative stress, inflammation, and endoplasmic reticulum stress-induced apoptosis. Therefore, our findings suggest that treatment with simvastatin may be a useful approach in the management strategy of ALD.     

Synthesis and In Vitro Antitumor Activity of Novel Chromenones Bearing Benzothiazole Moiety

Russian Journal of Bioorganic Chemistry - 6-(Benzo[d]thiazol-2-yl)-4-oxo-(4H)-chromene-3-carbaldehyde was utilized to construct a novel series of fused chromone bearing benzothiazole moiety, namely...     

Ameliorative role of Ziziphus spina-christi leaf extracts against hepatic injury induced by Plasmodium chabaudi infected erythrocytes

One of the most common deadliest parasitic diseases is Malaria. The biology and the pathogenesis of this fascinating parasite are not yet fully understood which make discovering effective alternative drugs a challenging task. Moreover, the emergence of resistant strains added an additional burden in the journey of malaria elimination. Traditional medicine used to be an alternative therapy choice owing to the presence of potent natural products. Ziziphus spina-christi (L.) considered being one of the common potent natural plant in gulf region and other nations. Therefore, this study designed to evaluate the ameliorative role of Z. spina-christi leaf extracts (ZSCLE) against Plasmodium chabaudi-induced hepatic injury. The study involved three groups were as follows; a vehicle control group, infected with 10⁶P. chabaudi-parasitized erythrocytes group and ZSCLE treated-infected mice with 10⁶P. chabaudi-parasitized erythrocytes group. The results showed a remarkable reduction of parasitemia level and notable reverse of the anemic picture among ZSCLE treated-infected mice. The effects of ZSCLE on the liver functions enzymes and on the histopathological pictures of liver were significant. It could be concluded that Z. spina-christi leaf extracts have a protective role against Plasmodium infection that also marked through significant restoration of hepatic oxidative markers.