Dead Shrimp Blues: A Global Assessment of Extinction Risk in Freshwater Shrimps (Crustacea: Decapoda: Caridea)

We present the first global assessment of extinction risk for a major group of freshwater invertebrates, caridean shrimps. The risk of extinction for all 763 species was assessed using the IUCN Red List criteria that include geographic ranges, habitats, ecology and past and present threats. The Indo-Malayan region holds over half of global species diversity, with a peak in Indo-China and southern China. Shrimps primarily inhabit flowing water; however, a significant subterranean component is present, which is more threatened than the surface fauna. Two species are extinct with a further 10 possibly extinct, and almost one third of species are either threatened or Near Threatened (NT). Threats to freshwater shrimps include agricultural and urban pollution impact over two-thirds of threatened and NT species. Invasive species and climate change have the greatest overall impact of all threats (based on combined timing, scope and severity of threats).     

Small molecule ago-allosteric modulators of the human glucagon-like peptide-1 (hGLP-1) receptor

Following our previous publication describing the biological profiles, we herein describe the structure-activity relationships of a core set of quinoxalines as the hGLP-1 receptor agonists. The most potent and efficacious compounds are 6,7-dichloroquinoxalines bearing an alkyl sulfonyl group at the C-2 position and a secondary alkyl amino group at the C-3 position. These findings serve as a valuable starting point for the discovery of more drug-like small molecule agonists for the hGLP-1 receptor.     

<Emphasis Type="Italic">Lysmata rafa</Emphasis>, a new species of peppermint shrimp (Crustacea,Caridea, Hippolytidae) from the subtropical western Atlantic

Lysmata rafa n. sp. is described from freshly collected specimens from the Keys West Lakes, Florida Keys, and from a museum specimen collected at Bear Cut, Biscayne Bay, Florida. The new species is morphologically most similar to the western Atlantic Lysmata rathbunae Chace, 1970 and the eastern Pacific Lysmata gracilirostris Wicksten, 2000, but can be distinguished from them by the number of carpal segments in the second pereiopod; the length and dentition of the rostrum; the shape and number of spines on the dactylus of the third to fifth pereiopods; and the absence of a tooth on the pterygostomial margin of the carapace. Despite being a shallow-water species, L. rafa n. sp. has extremely elongate walking legs and third maxilliped that are more typical to deep-water or cave dwelling carideans.     

Rapid, landscape scale responses in riparian tundra vegetation to exclusion of small and large mammalian herbivores

Productive tundra plant communities composed of a variety of fast growing herbaceous and woody plants are likely to attract mammalian herbivores. Such vegetation is likely to respond to different-sized herbivores more rapidly than currently acknowledged from the tundra. Accentuated by currently changing populations of arctic mammals there is a need to understand impacts of different-sized herbivores on the dynamics of productive tundra plant communities. Here we assess the differential effects of ungulate (reindeer) and small rodent herbivores (voles and lemmings) on high productive tundra vegetation. A spatially extensive exclosure experiment was run for three years on river sediment plains along two river catchments in low-arctic Norway. The river catchments were similar in species pools but differed in species abundance composition of both plants and vertebrate herbivores. Biomass of forbs, deciduous shrubs and silica-poor grasses increased by 40–50% in response to release from herbivory, whereas biomass of silica-rich grasses decreased by 50–75%. Hence both additive and compensatory effects of small rodents and reindeer exclusion caused these significant changes in abundance composition of the plant communities. Changes were also rapid, evident after only one growing season, and are among the fastest and strongest ever documented in Arctic vegetation. The rate of changes indicates a tight link between the dynamics of productive tundra vegetation and both small and large herbivores. Responses were however not spatially consistent, being highly different between the catchments. We conclude that despite similar species pools, variation in plant species abundance and herbivore species dynamics give different prerequisites for change.     

Predictive and prognostic impact of TP53 mutations and MDM2 promoter genotype in primary breast cancer patients treated with epirubicin or paclitaxel

Background

TP53 mutations have been associated with resistance to anthracyclines but not to taxanes in breast cancer patients. The MDM2 promoter single nucleotide polymorphism (SNP) T309G increases MDM2 activity and may reduce wild-type p53 protein activity. Here, we explored the predictive and prognostic value of TP53 and CHEK2 mutation status together with MDM2 SNP309 genotype in stage III breast cancer patients receiving paclitaxel or epirubicin monotherapy.

Experimental Design

Each patient was randomly assigned to treatment with epirubicin 90 mg/m² (n = 109) or paclitaxel 200 mg/m² (n = 114) every 3rd week as monotherapy for 4–6 cycles. Patients obtaining a suboptimal response on first-line treatment requiring further chemotherapy received the opposite regimen. Time from last patient inclusion to follow-up censoring was 69 months. Each patient had snap-frozen tumor tissue specimens collected prior to commencing chemotherapy.

Principal Findings

While TP53 and CHEK2 mutations predicted resistance to epirubicin, MDM2 status did not. Neither TP53/CHEK2 mutations nor MDM2 status was associated with paclitaxel response. Remarkably, TP53 mutations (p = 0.007) but also MDM2 309TG/GG genotype status (p = 0.012) were associated with a poor disease-specific survival among patients having paclitaxel but not patients having epirubicin first-line. The effect of MDM2 status was observed among individuals harbouring wild-type TP53 (p = 0.039) but not among individuals with TP53 mutated tumors (p>0.5).

Conclusion

TP53 and CHEK2 mutations were associated with lack of response to epirubicin monotherapy. In contrast, TP53 mutations and MDM2 309G allele status conferred poor disease-specific survival among patients treated with primary paclitaxel but not epirubicin monotherapy.     

Arachidonic acid randomizes endothelial cell motion and regulates adhesion and migration

Cell adhesion and migration are essential for the evolution, organization, and repair of living organisms. An example of a combination of these processes is the formation of new blood vessels (angiogenesis), which is mediated by a directed migration and adhesion of endothelial cells (ECs). Angiogenesis is an essential part of wound healing and a prerequisite of cancerous tumor growth. We investigated the effect of the amphiphilic compound arachidonic acid (AA) on EC adhesion and migration by combining live cell imaging with biophysical analysis methods. AA significantly influenced both EC adhesion and migration, in either a stimulating or inhibiting fashion depending on AA concentration. The temporal evolution of cell adhesion area was well described by a two-phase model. In the first phase, the spreading dynamics were independent of AA concentration. In the latter phase, the spreading dynamics increased at low AA concentrations and decreased at high AA concentrations. AA also affected EC migration; though the instantaneous speed of individual cells remained independent of AA concentration, the individual cells lost their sense of direction upon addition of AA, thus giving rise to an overall decrease in the collective motion of a confluent EC monolayer into vacant space. Addition of AA also caused ECs to become more elongated, this possibly being related to incorporation of AA in the EC membrane thus mediating a change in the viscosity of the membrane. Hence, AA is a promising non-receptor specific regulator of wound healing and angiogenesis.     

IL-33 Induces IL-9 Production in Human CD4+ T Cells and Basophils

IL-33, an IL-1 family member and ligand for the IL-1 receptor-related protein ST2, has been associated with induction of Th2 cytokines such as IL-4, IL-5, and IL-13. Here, we report that IL-33 can initiate IL-9 protein secretion in vitro in human CD4+ T cells and basophils isolated from peripheral blood. TGF-β has been described as a critical factor for IL-9 induction in Th2 cells; however, we found that TGF-β also induces co-production of IL-9 in purified, naïve (>99%) CD4⁺CD45RA⁺CD45RO⁻CD25⁻ T cells differentiated towards a Th1 profile. Subsequently, it was demonstrated that TGF-β is important, although not an absolute requirement, for IL-9 production in CD4+ T cells. IL-9 production by purified (>95%) human basophils, cultured for 24 h with IL-3 or IL-33, was found, with a strong synergy between the two, likely to be explained by the IL-3 upregulated ST2 expression. Collectively, these data indicate that barrier functioning cells are important for the regulation of IL-9 production by immune cells in inflamed tissue.     

Muscle wasting in cardiac cachexia

Cardiac cachexia is a serious complication of chronic heart failure which is characterized by complex changes that overall lead to a catabolic/anabolic imbalance resulting in body wasting and a poor prognosis. The wasting process affects all body components, but particularly the skeletal musculature, causing extreme fatigue and weakness, especially in cachectic heart failure patients. Available evidence suggests that several pathophysiologic pathways play a role in the muscle wasting process. Metabolic, neurohormonal, and immune abnormalities lead to an altered regulation of proliferation, differentiation, apoptosis, and metabolism in skeletal muscle, finally resulting in deterioration of the underlying cause with symptomatic exercise intolerance. Possible treatment strategies against muscle wasting and cachexia in chronic heart failure are also described here. As there is no validated therapy for cardiac cachexia yet, further research is necessary to find more therapeutic options for the wasting process.     

Quantitative trait locus (QTL) isogenic recombinant analysis: a method for high-resolution mapping of QTL within a single population

In the quest for fine mapping quantitative trait loci (QTL) at a subcentimorgan scale, several methods that involve the construction of inbred lines and the generation of large progenies of such inbred lines have been developed (Complex Trait Consortium 2003). Here we present an alternative method that significantly speeds up QTL fine mapping by using one segregating population. As a first step, a rough mapping analysis is performed on a small part of the population. Once the QTL have been mapped to a chromosomal interval by standard procedures, a large population of 1000 plants or more is analyzed with markers flanking the defined QTL to select QTL isogenic recombinants (QIRs). QIRs bear a recombination event in the QTL interval of interest, while other QTL have the same homozygous genotype. Only these QIRs are subsequently phenotyped to fine map the QTL. By focusing at an early stage on the informative individuals in the population only, the efforts in population genotyping and phenotyping are significantly reduced as compared to prior methods. The principles of this approach are demonstrated by fine mapping an erucic acid QTL of rapeseed at a subcentimorgan scale.     

The nature of lemming cycles on Wrangel: an island without small mustelids

Lemming cycles are a key process in the functioning of tundra ecosystems. Although it is agreed that trophic interactions are important in causing the cycles, the actual mechanism is disputed. Some researchers attribute a major role to predation by small mustelids such as stoats and least weasels. Here we present a 40-year time series of lemming dynamics from Wrangel Island and show statistically that lemmings do exhibit population cycles in the absence of small mustelids. The observed density fluctuations differed, however, from those observed elsewhere, with long cycles and possibly higher densities of lemmings during the low phase. These differences in the shape of the population cycles may be related to the unique species assemblage of Wrangel Island, where arctic foxes are the only year-round resident lemming predator, and to the high diversity of landscapes, microclimatic conditions, and plants on the island. Both spectral analysis and wavelet analysis show a change in period length from five?years in the 1970s to nearly eight?years in the 1990s and 2000s. This change in dynamics coincides with reports of dampening or fading out of lemming cycles that have been observed in several regions of the Arctic in recent decades. As in the other cases, the changed lemming dynamics on Wrangel Island may be related to ground icing in winter, which could delay peak years.