Morphological integration in the cranium during anuran metamorphosis

Summary We examined the role of thyroid hormone in mediating morphological integration between cranial cartilage and bone during anuran metamorphosis. Exogenous T₃ applied to premetamorphic tadpoles (Bombina orientalis) via intracranial implants of plastic micropellets precociously induced typical metamorphic changes in both tissues, but also dissociated the relative timing of developmental events between them. Morphological integration between the two primary cranial tissues is achieved in part by each tissue responding independently to endocrine factors and does not reflect a tight developmental coupling between them.     

Sharpening of knives for ultramicrotomy

Zusammenfassung Die Verfasser beschreiben eine Methode zur Herstellung von Messerschneiden zum Ultramikrotomgebrauch. Das Material des Messers besteht aus rostfreiem Stahl, der aus fast reinem Martensit aufgebaut ist. Das Schärfen wird auf einer speziellen Läppmaschine ausgeführt und umfasst zwei Phasen. Die erste, das Läppen gegen Gusseisen, gibt dem Messer einen Schneidenwinkel von 30°. Die zweite und letzte Schärfungsphase wird mit Spiegelglas ausgeführt und gibt einen Schneidenwinkel von 50°.     

Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk

Deletions on human chromosome 8p22-23 in prostate cancer cells and linkage studies in families affected with hereditary prostate cancer (HPC) have implicated this region in the development of prostate cancer. The macrophage scavenger receptor 1 gene (MSR1, also known as SR-A) is located at 8p22 and functions in several processes proposed to be relevant to prostate carcinogenesis. Here we report the results of genetic analyses that indicate that mutations in MSR1 may be associated with risk of prostate cancer. Among families affected with HPC, we identified six rare missense mutations and one nonsense mutation in MSR1. A family-based linkage and association test indicated that these mutations co-segregate with prostate cancer (P = 0.0007). In addition, among men of European descent, MSR1 mutations were detected in 4.4% of individuals affected with non-HPC as compared with 0.8% of unaffected men (P = 0.009). Among African American men, these values were 12.5% and 1.8%, respectively (P = 0.01). These results show that MSR1 may be important in susceptibility to prostate cancer in men of both African American and European descent.     

Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency

Apoptosis is a form of programmed cell death that is controlled by aspartate-specific cysteine proteases called caspases. In the immune system, apoptosis counters the proliferation of lymphocytes to achieve a homeostatic balance, which allows potent responses to pathogens but avoids autoimmunity. The CD95 (Fas, Apo-1) receptor triggers lymphocyte apoptosis by recruiting Fas-associated death domain (FADD), caspase-8 and caspase-10 proteins into a death-inducing signalling complex. Heterozygous mutations in CD95, CD95 ligand or caspase-10 underlie most cases of autoimmune lymphoproliferative syndrome (ALPS), a human disorder that is characterized by defective lymphocyte apoptosis, lymphadenopathy, splenomegaly and autoimmunity. Mutations in caspase-8 have not been described in ALPS, and homozygous caspase-8 deficiency causes embryonic lethality in mice. Here we describe a human kindred with an inherited genetic deficiency of caspase-8. Homozygous individuals manifest defective lymphocyte apoptosis and homeostasis but, unlike individuals affected with ALPS, also have defects in their activation of T lymphocytes, B lymphocytes and natural killer cells, which leads to immunodeficiency. Thus, caspase-8 deficiency in humans is compatible with normal development and shows that caspase-8 has a postnatal role in immune activation of naive lymphocytes.     

Analysis of the Plasmodium falciparum proteome by high-accuracy mass spectrometry

The annotated genomes of organisms define a 'blueprint' of their possible gene products. Post-genome analyses attempt to confirm and modify the annotation and impose a sense of the spatial, temporal and developmental usage of genetic information by the organism. Here we describe a large-scale, high-accuracy (average deviation less than 0.02 Da at 1,000 Da) mass spectrometric proteome analysis of selected stages of the human malaria parasite Plasmodium falciparum. The analysis revealed 1,289 proteins of which 714 proteins were identified in asexual blood stages, 931 in gametocytes and 645 in gametes. The last two groups provide insights into the biology of the sexual stages of the parasite, and include conserved, stage-specific, secreted and membrane-associated proteins. A subset of these proteins contain domains that indicate a role in cell-cell interactions, and therefore can be evaluated as potential components of a malaria vaccine formulation. We also report a set of peptides with significant matches in the parasite genome but not in the protein set predicted by computational methods.     

Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13

Since the sequencing of the first two chromosomes of the malaria parasite, Plasmodium falciparum, there has been a concerted effort to sequence and assemble the entire genome of this organism. Here we report the sequence of chromosomes 1, 3-9 and 13 of P. falciparum clone 3D7--these chromosomes account for approximately 55% of the total genome. We describe the methods used to map, sequence and annotate these chromosomes. By comparing our assemblies with the optical map, we indicate the completeness of the resulting sequence. During annotation, we assign Gene Ontology terms to the predicted gene products, and observe clustering of some malaria-specific terms to specific chromosomes. We identify a highly conserved sequence element found in the intergenic region of internal var genes that is not associated with their telomeric counterparts.     

Genome sequence of the human malaria parasite Plasmodium falciparum

The parasite Plasmodium falciparum is responsible for hundreds of millions of cases of malaria, and kills more than one million African children annually. Here we report an analysis of the genome sequence of P. falciparum clone 3D7. The 23-megabase nuclear genome consists of 14 chromosomes, encodes about 5,300 genes, and is the most (A + T)-rich genome sequenced to date. Genes involved in antigenic variation are concentrated in the subtelomeric regions of the chromosomes. Compared to the genomes of free-living eukaryotic microbes, the genome of this intracellular parasite encodes fewer enzymes and transporters, but a large proportion of genes are devoted to immune evasion and host-parasite interactions. Many nuclear-encoded proteins are targeted to the apicoplast, an organelle involved in fatty-acid and isoprenoid metabolism. The genome sequence provides the foundation for future studies of this organism, and is being exploited in the search for new drugs and vaccines to fight malaria.     

A new role for cryptochrome in a Drosophila circadian oscillator

Cryptochromes are flavin/pterin-containing proteins that are involved in circadian clock function in Drosophila and mice. In mice, the cryptochromes Cry1 and Cry2 are integral components of the circadian oscillator within the brain and contribute to circadian photoreception in the retina. In Drosophila, cryptochrome (CRY) acts as a photoreceptor that mediates light input to circadian oscillators in both brain and peripheral tissue. A Drosophila cry mutant, cryb, leaves circadian oscillator function intact in central circadian pacemaker neurons but renders peripheral circadian oscillators largely arrhythmic. Although this arrhythmicity could be caused by a loss of light entrainment, it is also consistent with a role for CRY in the oscillator. A peripheral oscillator drives circadian olfactory responses in Drosophila antennae. Here we show that CRY contributes to oscillator function and physiological output rhythms in the antenna during and after entrainment to light-dark cycles and after photic input is eliminated by entraining flies to temperature cycles. These results demonstrate a photoreceptor-independent role for CRY in the periphery and imply fundamental differences between central and peripheral oscillator mechanisms in Drosophila.     

Warm tropical sea surface temperatures in the Late Cretaceous and Eocene epochs

Climate models with increased levels of carbon dioxide predict that global warming causes heating in the tropics, but investigations of ancient climates based on palaeodata have generally indicated cool tropical temperatures during supposed greenhouse episodes. For example, in the Late Cretaceous and Eocene epochs there is abundant geological evidence for warm, mostly ice-free poles, but tropical sea surface temperatures are generally estimated to be only 15-23 degrees C, based on oxygen isotope palaeothermometry of surface-dwelling planktonic foraminifer shells. Here we question the validity of most such data on the grounds of poor preservation and diagenetic alteration. We present new data from exceptionally well preserved foraminifer shells extracted from impermeable clay-rich sediments, which indicate that for the intervals studied, tropical sea surface temperatures were at least 28-32 degrees C. These warm temperatures are more in line with our understanding of the geographical distributions of temperature-sensitive fossil organisms and the results of climate models with increased CO2 levels.     

An abrupt climate event in a coupled ocean-atmosphere simulation without external forcing

Temperature reconstructions from the North Atlantic region indicate frequent abrupt and severe climate fluctuations during the last glacial and Holocene periods. The driving forces for these events are unclear and coupled atmosphere-ocean models of global circulation have only simulated such events by inserting large amounts of fresh water into the northern North Atlantic Ocean. Here we report a drastic cooling event in a 15,000-yr simulation of global circulation with present-day climate conditions without the use of such external forcing. In our simulation, the annual average surface temperature near southern Greenland spontaneously fell 6-10 standard deviations below its mean value for a period of 30-40 yr. The event was triggered by a persistent northwesterly wind that transported large amounts of buoyant cold and fresh water into the northern North Atlantic Ocean. Oceanic convection shut down in response to this flow, concentrating the entire cooling of the northern North Atlantic by the colder atmosphere in the uppermost ocean layer. Given the similarity between our simulation and observed records of rapid cooling events, our results indicate that internal atmospheric variability alone could have generated the extreme climate disruptions in this region.