Diversification across a heterogeneous landscape

Adaptation to contrasting environments across a heterogeneous landscape favors the formation of ecotypes by promoting ecological divergence. Patterns of fitness variation in the field can show whether natural selection drives local adaptation and ecotype formation. However, to demonstrate a link between ecological divergence and speciation, local adaptation must have consequences for reproductive isolation. Using contrasting ecotypes of an Australian wildflower, Senecio lautus in common garden experiments, hybridization experiments, and reciprocal transplants, we assessed how the environment shapes patterns of adaptation and the consequences of adaptive divergence for reproductive isolation. Local adaptation was strong between ecotypes, but weaker between populations of the same ecotype. F1 hybrids exhibited heterosis, but crosses involving one native parent performed better than those with two foreign parents. In a common garden experiment, F2 hybrids exhibited reduced fitness compared to parentals and F1 hybrids, suggesting that few genetic incompatibilities have accumulated between populations adapted to contrasting environments. Our results show how ecological differences across the landscape have created complex patterns of local adaptation and reproductive isolation, suggesting that divergent natural selection has played a fundamental role in the early stages of species diversification.     

Notch3 is dispensable for thymocyte β-selection and Notch1-induced T cell leukemogenesis

Notch1 (N1) signaling induced by intrathymic Delta-like (DL) ligands is required for T cell lineage commitment as well as self-renewal during “β-selection” of TCRβ⁺ CD4⁻CD8⁻ double negative 3 (DN3) T cell progenitors. However, over-expression of the N1 intracellular domain (ICN1) renders N1 activation ligand-independent and drives leukemic transformation during β-selection. DN3 progenitors also express Notch3 (N3) mRNA, and over-expression of ligand-independent mutant N3 (ICN3) influences β-selection and drives T cell leukemogenesis. However, the importance of ligand-activated N3 in promoting β-selection and ICN1-induced T cell leukemogenesis has not been examined. To address these questions we generated mice lacking functional N3. We confirmed that DN3 progenitors express N3 protein using a N3-specific antibody. Surprisingly however, N3-deficient DN3 thymocytes were not defective in generating DP thymocytes under steady state conditions or in more stringent competition assays. To determine if N3 co-operates with N1 to regulate β-selection, we generated N1;N3 compound mutants. However, N3 deficiency did not exacerbate the competitive defect of N1^+/− DN3 progenitors, demonstrating that N3 does not compensate for limiting N1 during T cell development. Finally, N3 deficiency did not attenuate T cell leukemogenesis induced by conditional expression of ICN1 in DN3 thymocytes. Importantly, we showed that in contrast to N1, N3 has a low binding affinity for DL4, the most abundant intrathymic DL ligand. Thus, despite the profound effects of ectopic ligand-independent N3 activation on T cell development and leukemogenesis, physiologically activated N3 is dispensable for both processes, likely because N3 interacts poorly with intrathymic DL4.     

Identifying and Predicting Biological Risks Associated With Manufactured Nanoparticles in Aquatic Ecosystems

Nanotechnology has great potential for revolutionizing the treatment of disease, optimizing manufacturing processes and consumer products, and remediating polluted environments. Increased use and disposal of products containing nanoparticles will inevitably result in their accumulation in aquatic ecosystems via direct input and runoff from contaminated soils. Aquatic organisms are particularly susceptible to pollutants due to their large, fragile respiratory epithelium. This potential toxicity can be exacerbated by common stressors, such as changes in water temperature, salinity, pH, and oxygen levels, and must be considered in environmental risk assessments. The unique properties of manufactured nanoparticles present serious problems for risk assessment strategies, and there is a concern in the regulatory community that standard toxicological methods may be inadequate to address these compounds. Our capacity to detect and quantify nanoparticles is extremely limited, especially in complex biological, soil, or water samples. The distinctive chemistry and physical structure of each nanomaterial will determine its bioavailability, and these parameters can be altered over time or with changes in water chemistry. The use of advanced analytical techniques, such as functional genomics, proteomics, and metabolomics, can provide a global assessment of the biological response to a novel chemical and will be important in determining the potential toxicity of nanoparticles. Industry should adopt a proactive approach to identifying potential risks to aquatic ecosystems so that the benefits of nanotechnology can be fully realized.     

Neuronal HSF-1 coordinates the propagation of fat desaturation across tissues to enable adaptation to high temperatures in C. elegans

To survive elevated temperatures, ectotherms adjust the fluidity of membranes by fine-tuning lipid desaturation levels in a process previously described to be cell autonomous. We have discovered that, in Caenorhabditis elegans, neuronal heat shock factor 1 (HSF-1), the conserved master regulator of the heat shock response (HSR), causes extensive fat remodeling in peripheral tissues. These changes include a decrease in fat desaturase and acid lipase expression in the intestine and a global shift in the saturation levels of plasma membrane’s phospholipids. The observed remodeling of plasma membrane is in line with ectothermic adaptive responses and gives worms a cumulative advantage to warm temperatures. We have determined that at least 6 TAX-2/TAX-4 cyclic guanosine monophosphate (cGMP) gated channel expressing sensory neurons, and transforming growth factor ß (TGF-β)/bone morphogenetic protein (BMP) are required for signaling across tissues to modulate fat desaturation. We also find neuronal hsf-1 is not only sufficient but also partially necessary to control the fat remodeling response and for survival at warm temperatures. This is the first study to show that a thermostat-based mechanism can cell nonautonomously coordinate membrane saturation and composition across tissues in a multicellular animal.

In response to heat, ectotherms exhibit an adaptive response characterized by changes in membrane fluidity. This study in the nematode Caenorhabditis elegans shows that neuronal HSF-1 is critical for this remodeling, suggesting a neuronal thermostat-based mechanism that can non-cell-autonomously coordinate the animal’s response to heat.     

肝病患者肝组织IL-18结合蛋白的表达和分析

目的:探讨肝病患者肝脏组织白细胞介素18结合蛋白(interleukin-18 binding protein,IL-18BP)的表达水平及临床意义.方法:应用免疫组织化学技术检测41例原发性肝癌、9例慢性乙型肝炎、11例肝硬化、和5例正常肝组织中IL-18BP的表达情况,同时检测患者外周血IL-18BP的含量.结果:原发性肝癌的癌周组织IL-18BP表达量最高,与癌组织、肝硬化组织、慢性肝炎组织和正常肝组织评分值组间比较差异有统计学意义(P＜0.01);表达强度:癌周组织＞肝硬化＞肝癌＞慢性肝炎,正常组织无阳性表达(P＜0.01).IL-18BP在组织中的表达和血清中的含量相一致.结论:肝病患者IL-18BP表达水平随病情加重呈递增趋势.     

Is Sperm Ultrastructure Useful in Polychaete Systematics? An Example Using 20 Species of the Fabriciinae (Polychaeta: Sabellidae)

The utility of sperm morphology in the systematics of polychaetes has been questioned in the past. This doubt stems from a problem with methodology, not with sperm morphology. It is argued that sperm characters used in combination with other morphological features have utility at various hierarchical levels. As a test of this proposition males in species from each of the following 10 fabriciin genera: Augeneriella, Fabricia, Fabriciola, Fahricinuda, Manayunkia, Novafabricia, Parafabricia, Pseudofabricia, Pseudofabriciola and an undescribed new Genus A (Fitzhugh et al., in preparation), were examined in order to provide new characters for phylogenetic systematic studies. All species were found to have a dorsal sperm duct running beneath the faecal groove of the thoracic region. No sabellin sabellids or serpulids have this duct. The above Fabriciinae have spermatids developing in large clusters of several hundred cells. Serpulids and sabellins nearly always have sperm developing in tetrads or small groups. Fabriciins studied also have a sperm structure distinct from the Sabellinae and the Serpulidae. Proposed synapomorphies for the members of the Fabriciinae, based on sperm structure, include (1) a thick glycocalyx over the plasma membrane; (2) a distinctive nuclear projection, with an anterior thickening of the nuclear membrane; (3) a thickened. spiraling ridge of nuclear membrane; (4) an extra-axonemal sheath and (5) a unique sheath of mitochondrial material in the midpiece. Within the sub-family there were differences among species in sperm structure. This variability involves acrosome morphology; the structure of the sperm nucleus and nuclear projection; the spiral of thickened nuclear membrane; the structure of the extra-axonemal sheath; the mitochondrial sheath. The monophyly of the Fabriciinae (sensu Fitzhugh, 1991, 1993) is well supported by this analysis. The status of Caobangia is still unresolved and a close examination of this genus is warranted.     

The probability distribution for a random match between an experimental-theoretical spectral pair in tandem mass spectrometry

Proteomic techniques are fast becoming the main method for qualitative and quantitative determination of the protein content in biological systems. Despite notable advances, efficient and accurate analysis of high throughput proteomic data generated by mass spectrometers remains one of the major stumbling blocks in the protein identification problem. We present a model for the number of random matches between an experimental MS-MS spectrum and a theoretical spectrum of a peptide. The shape of the probability distribution is a function of the experimental accuracy, the number of peaks in the experimental spectrum, the length of the interval over which the peaks are distributed, and the number of theoretical spectral peaks in this interval. Based on this probability distribution, a goodness-of-fit tool can be used to yield fast and accurate scoring schemes for peptide identification through database search. In this paper, we describe one possible implementation of such a method and compare the performance of the resulting scoring function with that of SEQUEST. In terms of speed, our algorithm is roughly two orders of magnitude faster than the SEQUEST program, and its accuracy of peptide identification compares favorably to that of SEQUEST. Moreover, our algorithm does not use information related to the intensities of the peaks.     

Caenorhabditis elegans HOPS and CCZ-1 mediate trafficking to lysosome-related organelles independently of RAB-7 and SAND-1

As early endosomes mature, the SAND-1/CCZ-1 complex acts as a guanine nucleotide exchange factor (GEF) for RAB-7 to promote the activity of its effector, HOPS, which facilitates late endosome–lysosome fusion and the consumption of AP-3–containing vesicles. We show that CCZ-1 and the HOPS complex are essential for the biogenesis of gut granules, cell type–specific, lysosome-related organelles (LROs) that coexist with conventional lysosomes in Caenorhabditis elegans intestinal cells. The HOPS subunit VPS-18 promotes the trafficking of gut granule proteins away from lysosomes and functions downstream of or in parallel to the AP-3 adaptor. CCZ-1 also acts independently of AP-3, and ccz-1 mutants mistraffic gut granule proteins. Our results indicate that SAND-1 does not participate in the formation of gut granules. In the absence of RAB-7 activity, gut granules are generated; however, their size and protein composition are subtly altered. These observations suggest that CCZ-1 acts in partnership with a protein other than SAND-1 as a GEF for an alternate Rab to promote gut granule biogenesis. Point mutations in GLO-1, a Rab32/38-related protein, predicted to increase spontaneous guanine nucleotide exchange, specifically suppress the loss of gut granules by ccz-1 and glo-3 mutants. GLO-3 is known to be required for gut granule formation and has homology to SAND-1/Mon1–related proteins, suggesting that CCZ-1 functions with GLO-3 upstream of the GLO-1 Rab, possibly as a GLO-1 GEF. These results support LRO formation occurring via processes similar to conventional lysosome biogenesis, albeit with key molecular differences.