A proposed mechanism for intermediate atresia ani (AA), based on a porcine case of AA and hypospadias

BACKGROUND: Atresia Ani (AA) is one of the most common malformations of the lower gastrointestinal tract. It occurs in 1 in 1500 to 1 in 5000 human births. These patients suffer physically and psychologically from this disorder, and thus there is a research interest in the condition. There are 3 subcategories of AA: high, intermediate, and low. Each of these forms is likely related to separate etiological processes. METHODS: An anatomical study was performed on a porcine case of AA with a urorectal fistula and malformed urethra. RESULTS: This animal was found to have the intermediate form of AA. CONCLUSIONS: A new mechanism is hypothesized, distinct from that described for the high and low forms of AA. This proposed mechanism involves the persistence of the cloacal membrane. Evidence to support this hypothesis includes: location of the urorectal fistula in the region of the embryonic cloacal duct, the lack of anomalies usually seen in conjunction with AA associated with mutations of the Sonic Hedgehog gene, and the presence of a malformed urethra, which is significantly correlated to intermediate AA. This form of AA could be related to a failure of the cloacal membrane to break down at the appropriate time during urorectal separation.     

Intraluminal Drug Delivery to the Mouse Arteriovenous Fistula Endothelium

Delivery of therapeutic agents to enhance arteriovenous fistula (AVF) maturation can be administered either via intraluminal or external routes. The simple murine AVF model was combined with intraluminal administration of drug solution to the venous endothelium at the same time as fistula creation. Technical aspects of this model are discussed. Under general anesthesia, an abdominal incision is made and the aorta and inferior vena cava (IVC) are exposed. The infra-renal aorta and IVC are dissected for clamping. After proximal and distal clamping, the puncture site is exposed and a 25 G needle is used to puncture both walls of the aorta and into the IVC. Immediately after the puncture, a reporter gene-expressing viral vector was infused in the IVC via the same needle, followed by 15 min of incubation. The intraluminal administration method enabled more robust viral gene delivery to the venous endothelium compared to administration by the external route. This novel method of delivery will facilitate studies that explore the role of the endothelium in AVF maturation and enable intraluminal drug delivery at the time of surgical operation.     

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.

     

Mapping of balanced chromosome translocation breakpoints to the basepair level from microdissected chromosomes

The analysis of structural variants associated with specific phenotypic features is promising for the elucidation of the function of involved genes. There is, however, at present no approach allowing the rapid mapping of chromosomal translocation breakpoints to the basepair level from a single chromosome. Here we demonstrate that we have advanced both the microdissection and the subsequent unbiased amplification to an extent that breakpoint mapping to the basepair level has become possible. As a case in point we analysed the two breakpoints of a t(7;13) translocation observed in a patient with split hand/foot malformation (SHFM1). The amplification products of the der(7) and of the der(13) were hybridized to custom‐made arrays, enabling us to define primers at flanking breakpoint regions and thus to fine‐map the breakpoints to the basepair level. Consequently, our results will also contribute to a further delineation of causative mechanisms underlying SHFM1 which are currently unknown.     

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.     

Cerebellar cortical lamination and foliation require cyclin A2

The mammalian genome encodes two A-type cyclins, which are considered potentially redundant yet essential regulators of the cell cycle. Here, we tested requirements for cyclin A1 and cyclin A2 function in cerebellar development. Compound conditional loss of cyclin A1/A2 in neural progenitors resulted in severe cerebellar hypoplasia, decreased proliferation of cerebellar granule neuron progenitors (CGNP), and Purkinje (PC) neuron dyslamination. Deletion of cyclin A2 alone showed an identical phenotype, demonstrating that cyclin A1 does not compensate for cyclin A2 loss in neural progenitors. Cyclin A2 loss lead to increased apoptosis at early embryonic time points but not at post-natal time points. In contrast, neural progenitors of the VZ/SVZ did not undergo increased apoptosis, indicating that VZ/SVZ-derived and rhombic lip-derived progenitor cells show differential requirements to cyclin A2. Conditional knockout of cyclin A2 or the SHH proliferative target Nmyc in CGNP also resulted in PC neuron dyslamination. Although cyclin E1 has been reported to compensate for cyclin A2 function in fibroblasts and is upregulated in cyclin A2 null cerebella, cyclin E1 expression was unable to compensate for loss-of cyclin A2 function.     

Split-hand/feet malformation in three tamilian families and review of the reports from India

Split-hand/foot malformation (SHFM) is a rare condition which can be either syndromic or nonsyndromic. We report three unrelated pedigrees, one with autosomal dominant (AD) inheritance and the other two with autosomal recessive (AR) pattern. We also briefly review the published reports from India.