Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling

Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumours. Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumours of DLBCL patients, apparently reflecting the variation in tumour proliferation rate, host response and differentiation state of the tumour. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal centre B cells ('germinal centre B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'). Patients with germinal centre B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumours on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer.     

Pervasive density-dependent recruitment enhances seedling diversity in a tropical forest

Negative density-dependent recruitment of seedlings, that is, seeds of a given species are less likely to become established seedlings if the density of that species is high, has been proposed to be an important mechanism contributing to the extraordinary diversity of tropical tree communities because it can potentially prevent any particular species from usurping all available space, either in close proximity to seed sources or at relatively larger spatial scales. However, density-dependent recruitment does not necessarily enhance community diversity. Furthermore, although density-dependent effects have been found at some life stages in some species, no study has shown that density-dependent recruitment affects community diversity. Here we report the results of observations in a lowland, moist forest in the Republic of Panamá in which the species identities of 386,027 seeds that arrived at 200 seed traps were compared with the species identities of 13,068 seedlings that recruited into adjacent plots over a 4-year period. Across the 200 sites, recruit seedling diversity was significantly higher than seed diversity. Part of this difference was explained by interspecies differences in average recruitment success. Even after accounting for these differences, however, negative density-dependent recruitment contributes significantly to the increase in diversity from seeds to seedling recruits.     

Learning to Predict in Complex Biological Domains

1 Introduction1 Bioinformatics is a rapidly expanding field involving a significant contribution from the data mining community. Many different problems are grouped into the general category of bioinformatics, including protein secondary structure prediction, drug discovery, DNA microarray analysis, gene prediction and genome analysis [17]. In this paper, we focus on two particular problems in which data mining can contribute: drug discovery and protein secondary structure prediction. Both …     

Importance of the anti-serotonin effect for mounting behaviour in rats

Zusammenfassung «Mounting behaviour» bei Ratten wird nicht nur durch die Kombination Testosteron plus Parachlorphenylalanin hervorgerufen. Auch durch die Gabe von Testosteron in Kombination mit den Substanzen Mesorgydin, WA 335-BS und Methysergid, die unter anderem antiserotonergen Effekt haben, wird «mounting behaviour» bei männlichen Ratten ausgelöst. Aufgrund dieser Ergebnisse und zitierten Beobachtungen ist eine ursächliche Bedeutung zwischen dem Anti-Serotonin-Effekt und der Aktivierung des «mounting behaviour» bei männlichen Ratten anzunehmen. Die spezifische Wirkung der Substanz PCPA allein kann für dieses Verhalten nicht verantwortlich gemacht werden.     

Biochemical efficiency and intrinsic shortening speed in selected vertebrate fast and slow muscles

Summary The biochemical efficiency was measured in iodoacetate N₂ and NaCN-treated muscles by dividing the work done by the amount of phosphoryl creatine hydrolysed when contracting at their optimum velocity. An inverse relationship was found between the intrinsic speed of shortening (V_max) of the muscles and their mechanochemical efficiency.     

Extracellular but not intracellular application of peptide hormones activates pancreatic acinar cells.

Peptide hormones, like neurotransmitters, are traditionally thought to activate cells by interacting with receptor sites accessible only from the extracellular space. However, there is no available evidence that establishes whether intracellular injections of peptide secretagogues can or cannot initiate cell activation. In view of recent demonstration that peptide hormones can penetrate the intracellular space in some tissues and the reports that intracellular injections of the neurotransmitter, dopamine, into acinar cells of cockroach salivary gland cause stimulation it seems of fundamental importance to test directly whether introduction of peptide secretagogues inside acinar cells of mammalian exocrine tissue can induce cell activation without first interacting with the outer surface of the external cell membrane. The data presented here show that injections of the secretagogue peptides caerulein and bombesinnonapeptide (bombesin-NP) into pancreatic acinar cells fail to evoke the characteristic potential and conductance changes that are observed following extracellular applications of these peptides.