Contrasting movement and activity of large brown trout and rainbow trout in Silver Creek, Idaho

Recent radiotelemetry studies demonstrated that stream-dwelling trout are mobile, but few have compared sympatric species. We used radiotelemetry to simultaneously monitor positions of 20 brown trout and 21 rainbow trout from May or June 1994 to February 1995 in Silver Creek, a small spring-fed stream in south central Idaho. Our biweekly observations from May to September indicated that rainbow trout had larger home ranges (medians, 606 m v. 131 m) and moved greater distances (medians, 1109 m v. 208 m) than brown trout. Furthermore, rainbow trout used more positions than brown trout (means, 7 v. 3) over this interval. Hourly diel monitoring revealed no significant difference in 24-h home ranges of rainbow trout and brown trout (means, 77 m v. 105 m). However, activity patterns of the 2 species differed; rainbow trout activity was usually highest during the day, whereas brown trout activity tended to peak at night. Differences in foraging strategies and response to disturbance may be responsible for differences in mobility.     

Review of selenium in soils, plants, and animals in Nevada

Selenium is critical in livestock nutrition; forage can be either potentially deficient or toxic in this element. Selenium is accumulated in excessive amounts by a relatively few species of plants. Several of these plants, termed indicator species, occur in the western Great Basin; however, selenium toxicity is not a problem in Nevada for domestic livestock. The detection of marginal dietary deficiencies of selenium is of much greater economic importance to the livestock industry than an excess of this element. Selenium occurs as a trace element in the composition of various minerals. Selenium levels are very low in volcanic rocks of recent origin. Accumulations of this element require concentration through secondary dispersion and subsequent sedimentation. Therefore, excesses of selenium are usually associated with siltstone, sandstone, or other sedimentary rocks. Selenium is usually found in soils as selenate, a water-soluble mineral. The selenium concentration of plants is directly related to the selenate concentration in soil. In soils low in selenate, the ability of plants to accumulate selenium is similar. In soils with high levels of selenate, indicator species accumulate 10 times as much selenium as other species. The foliage of most indicator plants is generally avoided by grazing animals. Deficiencies in dietary selenium are associated with the occurrence of white muscle disease, retained placentas, and general unthriftiness of animals. Insufficient dietary selenium can be overcome through injection, intraluminal pellets, or supplementation with salt mixtures.     

Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing

Most patients with acute myeloid leukaemia (AML) die from progressive disease after relapse, which is associated with clonal evolution at the cytogenetic level. To determine the mutational spectrum associated with relapse, we sequenced the primary tumour and relapse genomes from eight AML patients, and validated hundreds of somatic mutations using deep sequencing; this allowed us to define clonality and clonal evolution patterns precisely at relapse. In addition to discovering novel, recurrently mutated genes (for example, WAC, SMC3, DIS3, DDX41 and DAXX) in AML, we also found two major clonal evolution patterns during AML relapse: (1) the founding clone in the primary tumour gained mutations and evolved into the relapse clone, or (2) a subclone of the founding clone survived initial therapy, gained additional mutations and expanded at relapse. In all cases, chemotherapy failed to eradicate the founding clone. The comparison of relapse-specific versus primary tumour mutations in all eight cases revealed an increase in transversions, probably due to DNA damage caused by cytotoxic chemotherapy. These data demonstrate that AML relapse is associated with the addition of new mutations and clonal evolution, which is shaped, in part, by the chemotherapy that the patients receive to establish and maintain remissions.     

Extrathymically generated regulatory T cells control mucosal TH2 inflammation

A balance between pro- and anti-inflammatory mechanisms at mucosal interfaces, which are sites of constitutive exposure to microbes and non-microbial foreign substances, allows for efficient protection against pathogens yet prevents adverse inflammatory responses associated with allergy, asthma and intestinal inflammation. Regulatory T (T(reg)) cells prevent systemic and tissue-specific autoimmunity and inflammatory lesions at mucosal interfaces. These cells are generated in the thymus (tT(reg) cells) and in the periphery (induced (i)T(reg) cells), and their dual origin implies a division of labour between tT(reg) and iT(reg) cells in immune homeostasis. Here we show that a highly selective blockage in differentiation of iT(reg) cells in mice did not lead to unprovoked multi-organ autoimmunity, exacerbation of induced tissue-specific autoimmune pathology, or increased pro-inflammatory responses of T helper 1 (T(H)1) and T(H)17 cells. However, mice deficient in iT(reg) cells spontaneously developed pronounced T(H)2-type pathologies at mucosal sites--in the gastrointestinal tract and lungs--with hallmarks of allergic inflammation and asthma. Furthermore, iT(reg)-cell deficiency altered gut microbial communities. These results suggest that whereas T(reg) cells generated in the thymus appear sufficient for control of systemic and tissue-specific autoimmunity, extrathymic differentiation of T(reg) cells affects commensal microbiota composition and serves a distinct, essential function in restraint of allergic-type inflammation at mucosal interfaces.     

Embryonic and extraembryonic stem cell lines derived from single mouse blastomeres

The most basic objection to human embryonic stem (ES) cell research is rooted in the fact that ES cell derivation deprives embryos of any further potential to develop into a complete human being. ES cell lines are conventionally isolated from the inner cell mass of blastocysts and, in a few instances, from cleavage stage embryos. So far, there have been no reports in the literature of stem cell lines derived using an approach that does not require embryo destruction. Here we report an alternative method of establishing ES cell lines-using a technique of single-cell embryo biopsy similar to that used in pre-implantation genetic diagnosis of genetic defects-that does not interfere with the developmental potential of embryos. Five putative ES and seven trophoblast stem (TS) cell lines were produced from single blastomeres, which maintained normal karyotype and markers of pluripotency or TS cells for up to more than 50 passages. The ES cells differentiated into derivatives of all three germ layers in vitro and in teratomas, and showed germ line transmission. Single-blastomere-biopsied embryos developed to term without a reduction in their developmental capacity. The ability to generate human ES cells without the destruction of ex utero embryos would reduce or eliminate the ethical concerns of many.     

Platensimycin is a selective FabF inhibitor with potent antibiotic properties

Bacterial infection remains a serious threat to human lives because of emerging resistance to existing antibiotics. Although the scientific community has avidly pursued the discovery of new antibiotics that interact with new targets, these efforts have met with limited success since the early 1960s. Here we report the discovery of platensimycin, a previously unknown class of antibiotics produced by Streptomyces platensis. Platensimycin demonstrates strong, broad-spectrum Gram-positive antibacterial activity by selectively inhibiting cellular lipid biosynthesis. We show that this anti-bacterial effect is exerted through the selective targeting of beta-ketoacyl-(acyl-carrier-protein (ACP)) synthase I/II (FabF/B) in the synthetic pathway of fatty acids. Direct binding assays show that platensimycin interacts specifically with the acyl-enzyme intermediate of the target protein, and X-ray crystallographic studies reveal that a specific conformational change that occurs on acylation must take place before the inhibitor can bind. Treatment with platensimycin eradicates Staphylococcus aureus infection in mice. Because of its unique mode of action, platensimycin shows no cross-resistance to other key antibiotic-resistant strains tested, including methicillin-resistant S. aureus, vancomycin-intermediate S. aureus and vancomycin-resistant enterococci. Platensimycin is the most potent inhibitor reported for the FabF/B condensing enzymes, and is the only inhibitor of these targets that shows broad-spectrum activity, in vivo efficacy and no observed toxicity.