Ediacaran metazoan reveals lophotrochozoan affinity and deepens root of Cambrian Explosion.

Through exceptional preservation, we establish a phylogenetic connection between Ediacaran and Cambrian metazoans. We describe the first three-dimensional, pyritized soft tissue in Namacalathus from the Ediacaran Nama Group, Namibia, which follows the underlying form of a stalked, cup-shaped, calcitic skeleton, with six radially arranged lobes projecting into an apical opening and lateral lumens. A thick body wall and probable J-shaped gut are present within the cup, and the middle layer of the often-spinose skeleton and skeletal pores are selectively pyritized, supporting an organic-rich composition and tripartite construction with possible sensory punctae. These features suggest a total group lophotrochozoan affinity. These morphological data support molecular phylogenies and demonstrates that the origin of modern lophotrochozoan phyla, and their ability to biomineralize, had deep roots in the Ediacaran.

Regional nutrient decrease drove redox stabilisation and metazoan diversification in the late Ediacaran Nama Group, Namibia.

The late Ediacaran witnessed an increase in metazoan diversity and ecological complexity, marking the inception of the Cambrian Explosion. To constrain the drivers of this diversification, we combine redox and nutrient data for two shelf transects, with an inventory of biotic diversity and distribution from the Nama Group, Namibia (~550 to ~538 Million years ago; Ma). Unstable marine redox conditions characterised all water depths in inner to outer ramp settings from ~550 to 547 Ma, when the first skeletal metazoans appeared. However, a marked deepening of the redoxcline and a reduced frequency of anoxic incursions onto the inner to mid-ramp is recorded from ~547 Ma onwards, with full ventilation of the outer ramp by ~542 Ma. Phosphorus speciation data show that, whilst anoxic ferruginous conditions were initially conducive to the drawdown of bioavailable phosphorus, they also permitted a limited degree of phosphorus recycling back to the water column. A long-term decrease in nutrient delivery from continental weathering, coupled with a possible decrease in upwelling, led to the gradual ventilation of the Nama Group basins. This, in turn, further decreased anoxic recycling of bioavailable phosphorus to the water column, promoting the development of stable oxic conditions and the radiation of new mobile taxa.

Controls on the evolution of Ediacaran metazoan ecosystems: A redox perspective.

A growing number of detailed geochemical studies of Ediacaran (635-541 Ma) marine successions have provided snapshots into the redox environments that played host to the earliest known metazoans. Whilst previous compilations have focused on the global evolution of Ediacaran water column redox chemistry, the inherent heterogeneity evident in palaeogeographically distinct environments demands a more dissected approach to better understand the nature, interactions and evolution of extrinsic controls on the development of early macrobenthic ecosystems. Here, we review available data of local-scale redox conditions within a palaeogeographic and sequence stratigraphic framework, to explore the mechanisms controlling water column redox conditions and their potential impact on the record of metazoans. The openly connected Laurentian margin, North America (632-540 Ma) and Nama basin, Namibia (550-538 Ma), and the variably restricted Yangtze Block, South China (635-520 Ma), show continued redox instability after the first fossil evidence for metazoans. This may support opportunistic benthic colonisation during periods of transient oxygenation amidst episodic upwelling of anoxic waters beneath a very shallow, fluctuating chemocline. The first skeletal metazoans appeared under conditions of continued redox stratification, such as those which characterise the Dengying Formation of the Yangtze Block and the Kuibis Subgroup of the Nama basin. Current data, however, suggests that successful metazoan reef-building demanded more persistent oxia. We propose that cratonic positioning and migration throughout the Ediacaran Period, in combination with gradually increasing dissolved oxygen loading, may have provided a first-order control on redox evolution through regulating circulation mechanisms in the Mirovian Ocean. Some unrestricted lower slope environments from mid-high latitudes benefited from sustained oxygenation via downwelling, whilst transit of isolated cratons towards more equatorial positions stifled pervasive ventilation either through ineffective surface ocean mixing, Ekman-induced upwelling, elevated surface ocean productivity or a combination of these processes.

Intraspecific variation in an Ediacaran skeletal metazoan: Namacalathus from the Nama Group, Namibia.

Namacalathus hermanastes is one of the oldest known skeletal metazoans, found in carbonate settings of the terminal Ediacaran (~550-541 million years ago [Ma]). The palaeoecology of this widespread, goblet-shaped, benthic organism is poorly constrained yet critical for understanding the dynamics of the earliest metazoan communities. Analysis of in situ assemblages from the Nama Group, Namibia (~548-541 Ma), shows that Namacalathus exhibited size variation in response to differing water depths, hydrodynamic conditions and substrate types. In low-energy, inner ramp environments, Namacalathus attains the largest average sizes but grew in transient, loosely aggregating, monospecific aggregations attached to microbial mats. In high-energy mid-ramp reefs, Namacalathus spatially segregated into different palaeoecological habitats with distinct size distributions. In outer ramp environments, individuals were small and formed patchy, dense, monospecific aggregations attached to thin microbial mats. Asexual budding is common in all settings. We infer that variations in size distribution in Namacalathus reflect differences in habitat heterogeneity and stability, including the longevity of mechanically stable substrates and oxic conditions. In the Nama Group, long-lived skeletal metazoan communities developed within topographically heterogeneous mid-ramp reefs, which provided diverse mechanically stable microbial substrates in persistently oxic waters, while inner and outer ramp communities were often ephemeral, developing during fleeting episodes of either oxia and/or substrate stability. We conclude that Namacalathus, which forms a component of these communities in the Nama Group, was a generalist that adapted to various palaeoecological habitats within a heterogeneous ecosystem landscape where favourable conditions persisted, and was also able to opportunistically colonise transiently hospitable environments. These early skeletal metazoans colonised previously unoccupied substrates in thrombolitic reefs and other microbial carbonate settings, and while they experienced relatively low levels of interspecific competition, they were nonetheless adapted to the diverse environments and highly dynamic redox conditions present in the terminal Ediacaran.

Low-oxygen waters limited habitable space for early animals.

The oceans at the start of the Neoproterozoic Era (1,000-541 million years ago, Ma) were dominantly anoxic, but may have become progressively oxygenated, coincident with the rise of animal life. However, the control that oxygen exerted on the development of early animal ecosystems remains unclear, as previous research has focussed on the identification of fully anoxic or oxic conditions, rather than intermediate redox levels. Here we report anomalous cerium enrichments preserved in carbonate rocks across bathymetric basin transects from nine localities of the Nama Group, Namibia (∼550-541 Ma). In combination with Fe-based redox proxies, these data suggest that low-oxygen conditions occurred in a narrow zone between well-oxygenated surface waters and fully anoxic deep waters. Although abundant in well-oxygenated environments, early skeletal animals did not occupy oxygen impoverished regions of the shelf, demonstrating that oxygen availability (probably >10 µM) was a key requirement for the development of early animal-based ecosystems.

Dynamic anoxic ferruginous conditions during the end-Permian mass extinction and recovery.

The end-Permian mass extinction, ∼252 million years ago, is notable for a complex recovery period of ∼5 Myr. Widespread euxinic (anoxic and sulfidic) oceanic conditions have been proposed as both extinction mechanism and explanation for the protracted recovery period, yet the vertical distribution of anoxia in the water column and its temporal dynamics through this time period are poorly constrained. Here we utilize Fe-S-C systematics integrated with palaeontological observations to reconstruct a complete ocean redox history for the Late Permian to Early Triassic, using multiple sections across a shelf-to-basin transect on the Arabian Margin (Neo-Tethyan Ocean). In contrast to elsewhere, we show that anoxic non-sulfidic (ferruginous), rather than euxinic, conditions were prevalent in the Neo-Tethys. The Arabian Margin record demonstrates the repeated expansion of ferruginous conditions with the distal slope being the focus of anoxia at these times, as well as short-lived episodes of oxia that supported diverse biota.

Early animals. Ediacaran metazoan reefs from the Nama Group, Namibia.

Reef-building in metazoans represents an important ecological innovation whereby individuals collectively enhance feeding efficiency and gain protection from competitors and predation. The appearance of metazoan reefs in the fossil record therefore indicates an adaptive response to complex ecological pressures. In the Nama Group, Namibia, we found evidence of reef-building by the earliest known skeletal metazoan, the globally distributed Cloudina, ~548 million years ago. These Cloudina reefs formed open frameworks without a microbial component but with mutual attachment and cementation between individuals. Orientated growth implies a passive suspension-feeding habit into nutrient-rich currents. The characteristics of Cloudina support the view that metazoan reef-building was promoted by the rise of substrate competitors and predators.

Karyotypic analysis of adult pluripotent stem cells.

Three categories of precursor cells have been identified in postnatal mammals: tissue-committed progenitor cells, germ layer lineage-committed stem cells and lineage-uncommitted pluripotent stem cells. Progenitor cells are the immediate precursors of differentiated tissues. Germ layer lineage stem cells can be induced to form multiple cell types belonging to their respective ectodermal, mesodermal, and endodermal embryological lineages. Pluripotent stem cells will form somatic cell types from all three primary germ layer lineages. Progenitor cells demonstrate a finite life span before replicative senescence and cell death occur. Both germ layer lineage stem cells and pluripotent stem cells are telomerase positive and display extensive capabilities for self-renewal. Stem cells which undergo such extensive replication have the potential for undergoing mutations that may subsequently alter cellular functions. Gross mutations in the genome may be visualized as chromosomal aneuploidy and/or chromosomes that appear aberrant. This study was designed to determine whether any gross genomic mutations occurred within the adult pluripotent stem cells. Karyotypic analysis was performed using pluripotent stem cells purified from adult male rats using established procedures. Giemsa Banding was used in conjunction with light microscopy to visualize metaphase chromosome spreads. To date over 800 metaphase spreads have been analyzed. We found that the metaphase spreads averaged 42 chromosomes and concluded that these pluripotent stem cells isolated from adult rats have a normal karyotype.

Albright hereditary osteodystrophy and del(2) (q37.3) in four unrelated individuals.

Albright hereditary osteodystrophy (AHO) is a condition with characteristic physical findings (short stature, obesity, round face, brachydactyly) but variable biochemical changes (pseudohypoparathyroidism, pseudopseudohypoparathyroidism). Most patients with AHO have decreased activity of the guanine nucleotide-binding protein (GS protein) that stimulates adenylyl cyclase. The gene encoding the alpha subunit of the GS protein (GNAS1) has been mapped to the long arm of chromosome 20. We describe 4 unrelated individuals with apparent AHO, associated with small terminal deletions of chromosome 2. All 4 patients had normal serum calcium levels consistent with pseudopseudohypoparathyroidism. Del(2) (q37) is the first consistent karyotypic abnormality that has been documented in AHO [Phelan et al., 1993: Am J Hum Genet 53:484]. The finding of the same small terminal deletion in 4 unrelated individuals with a similar phenotype suggests that a gene locus in the 2q37 region is important in the pathogenesis of Albright syndrome. The association of Albright syndrome and the GNAS1 locus on chromosome 20 is well documented. The observation of a second potential disease locus on chromosome 2 may help explain the heterogeneity observed in this disorder.

Increased mortality in neonates with low thyroxine values.

Serum thyroxine values were determined prospectively over a 6-month interval in 97 newborn infants with birth weight < 2200 gm or gestational age < 37 weeks. There were 89 survivors and 8 deaths. Infants with thyroxine values of < 2.5 micrograms/dl (32.2 nmol/L) had a significantly higher mortality rate (p < 0.001) compared with infants with higher thyroxine levels. In neonates there may exist a critical thyroxine value below which there is an increased risk of mortality.

A patient with partial duplication 2q and partial deficiency 11q.

A patient with partial duplication 2q and partial deficiency 11q is reported. The propositus was delivered at 30 weeks gestation, with a birth weight of 1,390 g. He had severe hyaline membrane disease, intraventricular hemorrhage, bronchopulmonary dysplasia, hypotonia, psychomotor retardation, hearing loss, and other anomalies including a short bitemporal diameter, prominent occiput, low-set ears, exophthalmos, short nose with depressed nasal root, downturned mouth corners, narrow high-arched palate, micrognathia, a deep longitudinal groove over the sacrococcygeal region, clinodactyly, and abnormal dermatoglyphics. Chromosome analysis showed the following karyotype: 46,XY,der11,t(2:11)(q32.2;q25)pat.

Hydatid disease of the pelvis.

The clinical and radiological features of five patients with hydatid cyst of the pelvis are presented. The cysts were found in the following sites: the broad ligament, the pararectal soft tissues, the greater omentum, the ala of the sacrum and in the retrovesical space. Hydatid disease should be considered in the differential diagnosis of unusual cystic swellings in the pelvis, particularly in patients who have lived in endemic areas.

Combined xanthine and sulphite oxidase defect due to a deficiency of molybdenum cofactor.

Increased urinary excretion of xanthine, hypoxanthine, sulphite, thiosulphate and decreased serum uric acid were observed in an infant with profound failure to thrive. Other clinical findings included refractory seizures, spastic quadriplegia and profound psychomotor retardation. The patient died at 20 months of age. There were no detectable activities for xanthine oxidase and sulphite oxidase in the postmortem liver. Urothione, which is the metabolic excretory product of the molybdenum cofactor for molybdoenzymes was not present in the urine. A deficiency of the molybdenum cofactor which is common to both xanthine and sulphite oxidase is presumed to be the metabolic defect responsible for the absent activities of both enzymes.

Radiological evaluation of asymmetrical limitation of hip abduction during the first year of life.

Asymmetrical limitation of abduction of the hip may be found on screening of children in the first year of life. The clinical features identified may occur in congenital dislocation of the hip but most infants do not have or develop hip dislocation. Radiological changes are present on the side of limitation of abduction and include a higher acetabular angle, retardation of femoral head epiphyseal development, pelvic obliquity and a rotational deformation of the pelvis in the transaxial plane. The appearances are postural deformities due to persistent infant positioning and are self-correcting. If aggressive treatment methods are to be avoided, the radiologist should not confuse these changes with those of congenital hip dislocation or subluxation.

Biochemical observations on a case of hepatic fructose-1,6-diphosphatase deficiency.

A case of hepatic fructose-1,6-diphosphatase deficiency is described. She presented with congenital bilateral cataracts, failure to thrive, hypoglycaemia and hyperlactacidaemia. A liver biopsy revealed normal levels of gluconeogenic enzymes except fructose-1,6-diphosphatase which was present at 30% of the level of the lower control values. The residual activity had a normal affinity for fructose-1,6-diphosphate, a decreased sensitivity for inhibition by fructose-2,6-diphosphate and an increased resistance toward conversion to the AMP-insensitive form of the enzyme. As a result of this mutation, the residual FDPase will always be maintained in the AMP-inhibited form.

Oral VP-16-213 in advanced bronchogenic carcinoma and toxic effects when combined with methotrexate.

Forty-six patients with histologically confirmed lung cancer received treatment with the cytotoxic drug VP-16-213 in a dose of 100 mg twice daily, given orally for five days. The overall objective response rate was 11 out of 46 (24%) or 11 of the 33 (33%) who survived to receive two cycles. The drug was effective in all histological types. Only one patient developed leucopenia. This demonstration of the safety of VP-16-213 and its effectiveness suggested that this drug might be used in combination chemotherapy. A series of pilot studies showed unexplained marrow toxicity when VP-16-123 combined with vincristine was given with either methotrexate of adriamycin.