Interactive effects of cadmium and all-trans-retinoic acid on the induction of forelimb ectrodactyly in C57BL/6 mice

BACKGROUND: Most toxicological studies have tested single chemical agents at relatively high doses, and fewer studies have addressed the toxic effects of chemical interactions. It is important to understand the toxicity of chemical mixtures in order to assess the more realistic risks of environmental and occupational exposures. A number of chemicals are known to induce a predominantly postaxial forelimb ectrodactyly in C57BL/6 mice, including acetazolamide, ethanol, cadmium, valproic acid, carbon dioxide, dimethadione, phenytoin, and 13-cis-retinoic acid and all-trans-retinoic acid (RA). In the present study, the interactive effects of coadministration of cadmium and RA on developing limbs were investigated. METHODS: Pregnant C57BL/6 mice were treated with different intraperitoneal (IP) doses of cadmium chloride (CdCl2) and/or RA on gestational day (GD) 9.5, and fetuses were collected on GD 18 and double stained for examination of skeletal defects. RESULTS: When RA was given simultaneously with cadmium, a significant increase in the incidence and severity of forelimb ectrodactyly (predominantly postaxial) was observed compared to the results with corresponding doses of cadmium or RA alone. When mice were exposed to subthreshold doses of both cadmium (0.5 mg/kg) and RA (1 mg/kg), the combined treatment exceeded the threshold, resulting in forelimb ectrodactyly in 19% of the fetuses. Moreover, coadministration of cadmium and RA at doses exceeding the respective thresholds showed a synergistic effect, that is, 92% of fetuses were found with the forelimb defect as opposed to 10% if the response were additive. CONCLUSIONS: The findings demonstrate that concurrent exposure to these teratogens can have a synergistic effect and that subteratogenic doses may combine to exceed a threshold.     

An unusual colon atresia in a calf: at the junction of the distal loop and transverse colon. A brief overview

Congenital defects are those abnormalities present at birth. During embryogenesis, many anomalies can occur. The primitive gut tube lengthens quickly and rotates, allowing the gastrointestinal tract acquire its final position and orientation. Because the colon of large animals is complex, most changes occur in this segment. Thus, in ruminants, colon atresia is the most frequent malformation, affecting mainly ascending colon, at the level of the spiral loop. There are no previous references about a very atypical colon atresia at the junction of distal loop and transverse colon, such we have described in a 5-day-old calf, after a history of abdominal distention and absence of feces at birth, even with a patent anal opening. Atresia coli was detected at distal position of the typical colon atresia, at the junction of distal loop and transverse colon. In addition, the distal blind end was bent into a U-shape supported by the mesocolon. Besides the anatomical findings of this worthwhile atresia coli we discuss its possible etiology, in which local factors, such as a compromised blood supply during embryogenesis, are more consistent than genetic factors. Finding out the causes of atresia coli would help to reduce its incidence, lessen animal suffering and economic loss.     

Metabolic profiling of mango cultivars to identify biomarkers for resistance against Fusarium infection

Infection of mango panicles and young leaf shoots by Fusarium results in significantly lower fruit yields. Some mango cultivars are known to be tolerant to blossom malformation, while others are highly susceptible. Previous researchers linked the ability of certain cultivars to confine Fusarium infection to the production of high levels of mangiferin. This study further elucidates the role of phenolic metabolites contributing to tolerance. Phenolic profiles of mature leaf extracts from cultivars with varying degrees of resistance to Fusarium infection were obtained by ultrahigh performance liquid chromatography–time-of-flight-mass detection. Chemometric models constructed from the data revealed a clear distinction between the profiles of tolerant and susceptible cultivars and permitted the identification of biomarkers associated with susceptibility to infection. The presence of elevated levels of mangiferin, maclurin and maclurin O-galloyl-glucoside in the leaves were associated with a higher degree of tolerance. In contrast, high levels of iriflophenone glucosides were linked to increased susceptibility of the cultivars to infection. These models can serve as an important tool to investigate appropriate cultivars, prior to their introduction to areas prone to the disease.     

Mayer-Rokitansky-Kuster-Hauser syndrome type II: A rare case

Mayer-Rokitansky-Kuster-Hauser (MRKH) is a malformation complex comprising absent vagina and absent or rudimentary uterus. MRKH syndrome may be attributed to an initial affection of the intermediate mesoderm consequently leading (by the end of the 4^th week of fetal life) to an alteration of the blastema of the cervicothoracicsomites and the pronephricducts. These latter subsequently induce the differentiation of the mesonephric and then the Wolffian and Mullerian ducts. There are very sparse such cases reported. We present a case of type II MRKH or Mullerian renal cervical somite association (i.e., Mullerian duct aplasia, renal dysplasia, and cervical somite anomalies).     

Complex selection associated with Hox genes in a natural population of lizards

Hox genes are recognized for their explanatory power of bilateral development. However, relatively little is known about natural variation in, and the evolutionary dynamics of, Hox genes within wild populations. Utilizing a natural population of sand lizards (Lacerta agilis), we screened HoxA13 for genetic variation and an association with incidence of offspring malformations. We found significant effects of parental genetic similarity and offspring sex, and their interaction, on risk of hatching malformed as an offspring. We also found within population genetic variation in HoxA13, and identified a significant effect of a three-way interaction among Hox genotype, parental genetic similarity, and offspring sex on the risk of hatching malformation. Since malformed offspring in this population do not survive to maturity, this study reveals complex and ongoing selection associated with Hox genes in a wild reptile population. Importantly, this demonstrates the utility of natural populations in unveiling microevolutionary processes shaping variation in highly conserved genes.     

The reproductive capacity of Spodoptera littoralis moths fed ascorbic acid analogs

D-ascorbic acid, L-dehydroascorbic acid, 6-chloro-6-deoxy-L-ascorbic acid, 6-bromo-6-deoxy-L-ascorbic acid and ascorbyl-2-sulfate were bioassayed per os on moths of Spodoptera littoralis (Boisd.). The activity of each of the analogs was compared with that of vitamin C and sucrose controls. D-ascorbic acid caused males to produce malformed spermatophores with no reduction in mating capacity. Females mated to these males layed infertile eggs and fecundity was lower than in females fed other analogs, L-ascorbic acid or sucrose diets. 6-chloro-6-deoxy-L-ascorbic acid reduced fertility and fecundity of the females, although this and other analogs did not affect the spermatophores. D-isoascorbic acid (=D-araboascorbic acid; D-erythorbic acid), D-glucoascorbic acid and all the other analogs were equally acquired by males microfed singly or at mating. The effect of D-optically active analogs on the spermatophore and the possible applications of the analogs in pest control are discussed.

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Résumé Les examens ont porté sur l'action des acides D-ascorbique, L-déhydroascorbique, 6-chloro-6-déoxy-L-ascorbique, 6-bromo-6-déoxy-L-ascorbique et l'ascorbyl-2-sulfate per os. Les actions de ces analogues de l'acide ascorbique ont été comparées à celles de témoins alimentés avec vitamine C et glucose. L'acide D-ascorbique a provoqué la formation de spermatophores anormaux sans qu'il y ait eu réduction de l'activité sexuelle. Les femelles inséminées par ces mâles ont pondu des oeufs stériles, et leur fécondité était inférieure à celles de femelles alimentées sur des régimes contenant des analogues L de l'acide ascorbique ou du sucrose. L'acide 6-chloro-6-déoxy-L-ascorbique et l'ascorbyl-2-sulfate ont réduit la fécondité et la fertilité mais ces analogues n'avaient pas altéré la formation des spermatophores. Les consommations des différents analogues proposés séparément par microalimentation ou au moment de l'accouplement ne diffèrent pas significativement. La discussion a porté sur l'action des analogues dextrogyres sur le spermatophore et l'utilisation de ces analogues dans la protection des cultures.

     

Ethanolic extract of mango (Mangifera indica L.) malformed inflorescence as effective antifungal agent

Mango (Mangifera indica L.) suffers from floral and vegetative malformation and crop production is seriously affected. The anti-fungal activity of ethanolic extract of malformed mango inflorescence was observed at different concentrations (1000, 2000, 3000, 4000 and 5000 μl/ml) against 10 fungi, viz., Ustilago cynodontis, Cercospora cajani, Sphaerotheca sp., Cercospora sp., Alternaria solani, Bipolaris sp., Helminthosporium sp., Curvularia sp., Fusarium udum and Alternaria cajani. Spore germination of most of the fungi was inhibited at 5000 μg/ml. Some of them were also susceptible at 3000 or 4000 μg/ml concentration. Analysis of phenolic acids by high performance liquid chromatography (HPLC) showed 18 peaks in the extract, but only four could be identified, viz., capachin, gallic, benzoic and cinnamic acids. Because of the high efficacy of ethanolic extract of malformed mango inflorescence, its use under field conditions to control some plant diseases has been suggested.     

Regression and persistence: remodelling in a tissue engineered axial vascular assembly

In later stages of vasculoangiogenesis a vascular network is going through a metamorphosis for optimal perfusion and economy of energy. In this study we make a quantitative approach to phenomena of remodelling in a bioartificial neovascular network and suggest variance of calibre as a parameter of neovascular maturation. For this study, 18 male Lewis rats were subjected to the AV loop operation in combination with a hard porous biogenic matrix and an isolation chamber. The animals were allocated into three groups for different explantation intervals set to 2, 4 and 8 weeks, respectively. Collective attributes like vascular density, percent fractional area and variance of calibre were evaluated for a predefined region of interest (ROI). Late morphogenesis was evaluated by means of scanning electron microscopy. After the fourth week the absolute number of vessels within the ROI decreased (P < 0.03) whereas, on the contrary, the fractional area of all segments increased (P < 0.02). The variance in calibre was significantly increased in the 8‐week group (P < 0.05). Lymphatic growth after week 4, early pericyte migration as well as intussusceptive angiogenesis were identified immunohistologically. Phenomena of remodelling were evaluated quantitatively in a neovascular network and variance could be proposed as a parameter of net vascular maturation.     

Loss of unc45a precipitates arteriovenous shunting in the aortic arches

Aortic arch malformations are common congenital disorders that are frequently of unknown etiology. To gain insight into the factors that guide branchial aortic arch development, we examined the process by which these vessels assemble in wild type zebrafish embryos and in kurzschluss^tr12 (kus^tr12) mutants. In wild type embryos, each branchial aortic arch first appears as an island of angioblasts in the lateral pharyngeal mesoderm, then elaborates by angiogenesis to connect to the lateral dorsal aorta and ventral aorta. In kus^tr12 mutants, angioblast formation and initial sprouting are normal, but aortic arches 5 and 6 fail to form a lumenized connection to the lateral dorsal aorta. Blood enters these blind-ending vessels from the ventral aorta, distending the arteries and precipitating fusion with an adjacent vein. This arteriovenous malformation (AVM), which shunts nearly all blood directly back to the heart, is not exclusively genetically programmed, as its formation correlates with blood flow and aortic arch enlargement. By positional cloning, we have identified a nonsense mutation in unc45a in kus^tr12 mutants. Our results are the first to ascribe a role for Unc45a, a putative myosin chaperone, in vertebrate development, and identify a novel mechanism by which an AVM can form.