A clinical and experimental overview of sirenomelia: insight into the mechanisms of congenital limb malformations

Sirenomelia, also known as sirenomelia sequence, is a severe malformation of the lower body characterized by fusion of the legs and a variable combination of visceral abnormalities. The causes of this malformation remain unknown, although the discovery that it can have a genetic basis in mice represents an important step towards the understanding of its pathogenesis. Sirenomelia occurs in mice lacking Cyp26a1, an enzyme that degrades retinoic acid (RA), and in mice that develop with reduced bone morphogenetic protein (Bmp) signaling in the caudal embryonic region. The phenotypes of these mutant mice suggest that sirenomelia in humans is associated with an excess of RA signaling and a deficit in Bmp signaling in the caudal body. Clinical studies of sirenomelia have given rise to two main pathogenic hypotheses. The first hypothesis, based on the aberrant abdominal and umbilical vascular pattern of affected individuals, postulates a primary vascular defect that leaves the caudal part of the embryo hypoperfused. The second hypothesis, based on the overall malformation of the caudal body, postulates a primary defect in the generation of the mesoderm. This review gathers experimental and clinical information on sirenomelia together with the necessary background to understand how deviations from normal development of the caudal part of the embryo might lead to this multisystemic malformation.     

Digestive strategies and food choice in mantled howler monkeys Alouatta palliata mexicana: bases of their dietary flexibility

Mantled howler monkeys (Alouatta palliata) occupy a wide variety of tropical habitats and are the most folivorous of New World primates. However, their diet may include fruits, buds, petioles, and flowers, as well as leaves, suggesting they must cope with variations in the nutrient composition of their food. We studied the physiological basis of the dietary flexibility of these monkeys by comparing food choice, digestive performance and patterns of digesta flow in six adults, fed diets of either leaves or a mixture of fruit and leaves. Although monkeys ate similar amounts of the two diets, they ingested more digestible protein when offered the leaf diet, on which they lost body mass, but they ingested much more soluble sugars when offered fruit and leaves on which they gained mass. Digestibilities of dry matter, fat, energy and fibre did not differ between diets, but those of crude protein, soluble sugars and minerals were higher on the fruit–leaf diet. Mean retention times in the gut of solute (Co-EDTA) and particulate markers (Cr-mordanted cell walls) did not differ between diets, but on both diets the monkeys retained the particulate marker (mean retention time ca 55 h) for longer than they did the solute marker (MRT ca 50 h). A lack of selective retention of solutes and small particles in the gastro-intestinal tract of howler monkeys probably restricts them to mixed diets but their digestive strategy is sufficiently flexible to allow them to feed on a diet of leaves when fruit is unavailable.     

Coalitions and male–male behavior in <Emphasis Type="Italic">Alouatta palliata</Emphasis>

Coalitions influence the establishment and maintenance of social relationships among males in primate species. In this study, we compare the social behavior of males between two groups of Alouatta palliata: a group that was recently taken over by a coalition of two males (Mt), and a group that had a stable composition for at least 9 months (Rh). We predicted that coalition partners would be more cooperative and less competitive than dyads formed by immigrant and long-term resident males, and dyads formed by long-term resident males. Additionally, we predicted that these dyadic trends should be reflected in more competition and less cooperation in the group that was taken over. As predicted, the coalition partners of Mt showed the highest levels of cooperation among all dyads and the second lowest rate of agonism. Cooperation was higher in the group that had a stable composition. Results from this study suggest that the social relationships of male mantled howlers vary as a function of familiarity between males and that in the context of coalitionary takeovers, coalitionary males are highly cooperative. Cooperation is lower in groups recently taken over and competition is more intense, perhaps as a consequence of the process of establishment and reorganization of power relationships within some dyads. In the future, we must determine the frequency of coalitionary takeovers in this population and assess its ultimate consequences for male–male social relationships.     

The action of L-cysteine in acute cobalt chloride intoxication

A study in rats was made of the effects produced by L-cysteine on the acute toxicity of cobalt chloride given orally and intraperitoneally. The decrease in lethality was absolute for the different doses tested, except when the CoCl2 was given orally and L-cysteine intraperitoneally in which only 40% efficiency was obtained. No specially significant changes were observed in the blood parameters of the animals treated with the CoCl2-cysteine complex after one week. Significant differences were noted between serum parameters: glucose, triglycerides and cholesterol, measured in rats after twelve hours of receiving the CoCl2-cysteine complex, compared with the same parameters measured when the CoCl2 was given without complex.     

Preliminary taphonomic approach to “Lo Hueco” palaeontological site (Upper Cretaceous,Cuenca, Spain)

“Lo Hueco” encloses an extraordinary upper Campanian-lower Maastrichtian fossil assemblage, composed mainly of vertebrates but also plants and invertebrates, and concentrated in a sandy channel structure (C), two grey marly mudstone levels (G1 and G2) and the lower part of a red marly mudstone level (R2). Regarding biostratinomy, the C structure (interpreted as a distributary sandy channel) contains numerous highly altered and randomly distributed macrofossils. The G1 level (the proximal part of a flooded muddy plain) preserves several totally or partially articulated specimens, mainly sauropods, with low degree of scattering and preferred orientation with respect to C. The G2 level (the distal part of a flooded muddy plain) and the lower part of the R2 level (the dried part of a muddy plain) contain numerous rarely articulated and randomly scattered macrofossils. Concerning fossil diagenesis, macroscopically, most bones present a first infilling of gypsum in spongy cavities, a ferruginous crust over outer surfaces and a second precipitation of gypsum over outer surfaces and eventually crossing the ferruginous crust and the first infilling of gypsum. Microscopically, most bones from the C structure and the G1 level additionally show radial microcracks in secondary osteons and ferruginous rings in Haversian channels. Given their particular geological and taphonomic characteristics, the C structure, the G1 and G2 levels and the lower part of the R2 level constitute four distinct taphofacies or bonebeds.     

Toll‐like receptor 4 is activated by platinum and contributes to cisplatin‐induced ototoxicity

Toll‐like receptor 4 (TLR4) recognizes bacterial lipopolysaccharide (LPS) and can also be activated by some Group 9/10 transition metals, which is believed to mediate immune hypersensitivity reactions. In this work, we test whether TLR4 can be activated by the Group 10 metal platinum and the platinum‐based chemotherapeutic cisplatin. Cisplatin is invaluable in childhood cancer treatment but its use is limited due to a permanent hearing loss (cisplatin‐induced ototoxicity, CIO) adverse effect. We demonstrate that platinum and cisplatin activate pathways downstream of TLR4 to a similar extent as the known TLR4 agonists LPS and nickel. We further show that TLR4 is required for cisplatin‐induced inflammatory, oxidative, and cell death responses in hair cells in vitro and for hair cell damage in vivo. Finally, we identify a TLR4 small molecule inhibitor able to curtail cisplatin toxicity in vitro. Thus, our findings indicate that TLR4 is a promising therapeutic target to mitigate CIO.     

Seabird bycatch in the Southwest Atlantic: interaction with the Uruguayan pelagic longline fishery

This paper analyzes the spatiotemporal variation and the causes of seabird bycatch by the Uruguayan pelagic longline fleet in a region of the Atlantic Ocean where the world’s highest historical rates of seabird bycatch were recorded. The study is based on data obtained by the Uruguayan Observers Program in 29 trips, conducted from 1998 to 2004, totalling about 648,000 hooks. The bird capture per unit of effort (BCPUE) for the studied period was 0.42 birds/1,000 hooks. The highest BCPUE values were recorded in the period May–November. Three zones were identified, with BCPUEs of 2.50 birds/1,000 hooks (very high); 0.78 birds/1,000 hooks (high) and 0.04 birds/1,000 hooks (low). Though these BCPUE values are lower than those historically reported, some are still high in global terms. Night setting was found to be effective in reducing seabird bycatch, but it is necessary to implement additional measures as seabirds have access to bait also by night, especially during the more luminous moon phases.