Cutaneous cancer stem cells: beta-catenin strikes again

Cancer stem cells (CSCs) are a subpopulation of tumor cells that retain properties of tissue-specific stem cells, including the ability to self-renew. In a recent article in Nature, Malanchi et al. (2008) identified a population of CD34(+) cells in epidermal tumors that require beta-catenin signaling to maintain a CSC phenotype.     

Nitrate leaching and soil nitrous oxide emissions diminish with time in a hybrid poplar short‐rotation coppice in southern Germany

Hybrid poplar short‐rotation coppices (SRC) provide feedstocks for bioenergy production and can be established on lands that are suboptimal for food production. The environmental consequences of deploying this production system on marginal agricultural land need to be evaluated, including the investigation of common management practices i.e., fertilization and irrigation. In this work, we evaluated (1) the soil‐atmosphere exchange of carbon dioxide, methane, and nitrous oxide (N₂O); (2) the changes in soil organic carbon (SOC) stocks; (3) the gross ammonification and nitrification rates; and (4) the nitrate leaching as affected by the establishment of a hybrid poplar SRC on a marginal agricultural land in southern Germany. Our study covered one 3‐year rotation period and 2 years after the first coppicing. We combined field and laboratory experiments with modeling. The soil N₂O emissions decreased from 2.2 kg N₂O‐N ha^?1 a^?1 in the year of SRC establishment to 1.1–1.4 kg N₂O‐N ha^?1 a^?1 after 4 years. Likewise, nitrate leaching reduced from 13 to 1.5–8 kg N ha^?1 a^?1. Tree coppicing induced a brief pulse of soil N₂O flux and marginal effects on gross N turnover rates. Overall, the N losses diminished within 4 years by 80% without fertilization (irrespective of irrigation) and by 40% when 40–50 kg N ha^?1 a^?1 were applied. Enhanced N losses due to fertilization and the minor effect of fertilization and irrigation on tree growth discourage its use during the first rotation period after SRC establishment. A SOC accrual rate of 0.4 Mg C ha^?1 a^?1 (uppermost 25 cm, P = 0.2) was observed 5 years after the SRC establishment. Overall, our data suggest that SRC cultivation on marginal agricultural land in the region is a promising option for increasing the share of renewable energy sources due to its net positive environmental effects.     

A novel mouse Cre‐driver line targeting Perilipin 2‐expressing cells in the neonatal lung

Pulmonary diseases such as chronic obstructive pulmonary disease, lung fibrosis, and bronchopulmonary dysplasia are characterized by the destruction or malformation of the alveolar regions of the lung. The underlying pathomechanisms at play are an area of intense interest since these mechanisms may reveal pathways suitable for interventions to drive reparative processes. Lipid‐laden fibroblasts (lipofibroblasts) express the Perilipin 2 (Plin2) gene‐product, PLIN2, commonly called adipose‐differentiation related protein (ADRP). These cells are also thought to play a role in alveolarization and repair after injury to the alveolus. Progress in defining the functional contribution of lipofibroblasts to alveolar generation and repair is hampered by a lack of in vivo tools. The present study reports the generation of an inducible mouse Cre‐driver line to target cells of the ADRP lineage. Robust Cre‐mediated recombination in this mouse line was detected in mesenchymal cells of the postnatal lung, and in additional organs including the heart, liver, and spleen. The generation and validation of this valuable new tool to genetically target, manipulate, and trace cells of the ADRP lineage is critical for assessing the functional contribution of lipofibroblasts to lung development and repair.     

High-throughput characterization of photocrosslinker-bearing ion channel variants to map residues critical for function and pharmacology

Incorporation of noncanonical amino acids (ncAAs) can endow proteins with novel functionalities, such as crosslinking or fluorescence. In ion channels, the function of these variants can be studied with great precision using standard electrophysiology, but this approach is typically labor intensive and low throughput. Here, we establish a high-throughput protocol to conduct functional and pharmacological investigations of ncAA-containing human acid-sensing ion channel 1a (hASIC1a) variants in transiently transfected mammalian cells. We introduce 3 different photocrosslinking ncAAs into 103 positions and assess the function of the resulting 309 variants with automated patch clamp (APC). We demonstrate that the approach is efficient and versatile, as it is amenable to assessing even complex pharmacological modulation by peptides. The data show that the acidic pocket is a major determinant for current decay, and live-cell crosslinking provides insight into the hASIC1a–psalmotoxin 1 (PcTx1) interaction. Further, we provide evidence that the protocol can be applied to other ion channels, such as P2X2 and GluA2 receptors. We therefore anticipate the approach to enable future APC-based studies of ncAA-containing ion channels in mammalian cells.

This study describes a method to rapidly screen hundreds of ion channel variants containing non-canonical amino acids. A proof-of-principle introducing photocrosslinking non-canonical amino acids into the human ion channel hASIC1a shows how this approach can provide insights into function and pharmacology.     

Therapy of ankylosing spondylitis and other spondyloarthritides: established medical treatment, anti-TNF-α therapy and other novel approaches

Therapeutic options for patients with more severe forms of spondyloarthritis (SpA) have been rather limited in recent decades. There is accumulating evidence that anti-tumor-necrosis-factor (anti-TNF) therapy is highly effective in SpA, especially in ankylosing spondylitis and psoriatic arthritis. The major anti-TNF-α agents currently available, infliximab (Remicade^®) and etanercept (Enbrel^®), are approved for the treatment of rheumatoid arthritis (RA) in many countries. In ankylosing spondylitis there is an unmet medical need, since there are almost no disease-modifying antirheumatic drugs (DMARDs) available for severely affected patients, especially those with spinal manifestations. Judging from recent data from more than 300 patients with SpA, anti-TNF therapy seems to be even more effective in SpA than in rheumatoid arthritis. However, it remains to be shown whether patients benefit from long-term treatment, whether radiological progression and ankylosis can be stopped and whether long-term biologic therapy is safe.     

Three new species of the genus Leveillula from Iran

 Based on molecular and morphological studies, Leveillula guilanensis sp. nov. on Chondrilla juncea, L. lactucae-serriolae sp. nov. on Lactuca serriola, and L. mindii sp. nov. on Mindium laevigatum are described from Iran. Received: May 7, 2002 / Accepted: September 5, 2002 Correspondence to:S. Takamatsu     

The DExH/D box protein HEL/UAP56 is essential for mRNA nuclear export in Drosophila.

Dbp5 is the only member of the DExH/D box family of RNA helicases that is directly implicated in the export of messenger RNAs from the nucleus of yeast and vertebrate cells. Dbp5 localizes in the cytoplasm and at the cytoplasmic face of the nuclear pore complex (NPC). In an attempt to identify proteins present in a highly enriched NPC fraction, two other helicases were detected: RNA helicase A (RHA) and UAP56. This suggested a role for these proteins in nuclear transport. Contrary to expectation, we show that the Drosophila homolog of Dbp5 is not essential for mRNA export in cultured Schneider cells. In contrast, depletion of HEL, the Drosophila homolog of UAP56, inhibits growth and results in a robust accumulation of polyadenylated RNAs within the nucleus. Consequently, incorporation of [35S]methionine into newly synthesized proteins is inhibited. This inhibition affects the expression of both heat-shock and non-heat-shock mRNAs, as well as intron-containing and intronless mRNAs. In HeLa nuclear extracts, UAP56 preferentially, but not exclusively, associates with spliced mRNAs carrying the exon junction complex (EJC). We conclude that HEL is essential for the export of bulk mRNA in Drosophila. The association of human UAP56 with spliced mRNAs suggests that this protein might provide a functional link between splicing and export.