Photo-identification and satellite telemetry connect southern right whales from South Georgia Island (Islas Georgias del Sur) with multiple feeding and calving grounds in the southwest Atlantic

The sub-Antarctic waters of South Georgia Island (Islas Georgias del Sur, SG/IG) are a regularly visited feeding ground for southern right whales (Eubalaena australis, SRW) in the southwest Atlantic. Satellite telemetry and photo-identification records were compared to better understand the role of SG/IG in the SRW migratory network. We present the first insights from SRW satellite-tracked from the SG/IG feeding ground, habitat use patterns in the Scotia Arc, and movements to Antarctic habitats. Photo-identification comparisons to calving and feeding areas across the South Atlantic and a review of sightings of cetaceans reported from Bird Island (west of SG/IG) since 1979 illuminate long-term habitat use patterns in SG/IG. We present the first recorded migratory movement between SG/IG and multiple countries: Argentina, Uruguay, and Brazil. Photo-identification (1) linked SG/IG to a female SRW with a long-term sighting history in Brazil, and (2) provided the first match between SG/IG and the western Antarctic Peninsula, suggesting the latter could extend the feeding area for southwest Atlantic SRW. Satellite tracking and opportunistic sightings suggest that shelf and coastal waters west of SG/IG represent an important multi-season SRW feeding habitat and add to our overall understanding of habitats and ranges occupied by recovering southwest Atlantic SRW.     

Classifying behavior from short‐interval biologging data: An example with GPS tracking of birds

1. Recent advances in digital data collection have spurred accumulation of immense quantities of data that have potential to lead to remarkable ecological insight, but that also present analytic challenges. In the case of biologging data from birds, common analytical approaches to classifying movement behaviors are largely inappropriate for these massive data sets.
2. We apply a framework for using K‐means clustering to classify bird behavior using points from short time interval GPS tracks. K‐means clustering is a well‐known and computationally efficient statistical tool that has been used in animal movement studies primarily for clustering segments of consecutive points. To illustrate the utility of our approach, we apply K‐means clustering to six focal variables derived from GPS data collected at 1–11 s intervals from free‐flying bald eagles (Haliaeetus leucocephalus) throughout the state of Iowa, USA. We illustrate how these data can be used to identify behaviors and life‐stage‐ and age‐related variation in behavior.
3. After filtering for data quality, the K‐means algorithm identified four clusters in >2 million GPS telemetry data points. These four clusters corresponded to three movement states: ascending, flapping, and gliding flight; and one non‐moving state: perching. Mapping these states illustrated how they corresponded tightly to expectations derived from natural history observations; for example, long periods of ascending flight were often followed by long gliding descents, birds alternated between flapping and gliding flight.
4. The K‐means clustering approach we applied is both an efficient and effective mechanism to classify and interpret short‐interval biologging data to understand movement behaviors. Furthermore, because it can apply to an abundance of very short, irregular, and high‐dimensional movement data, it provides insight into small‐scale variation in behavior that would not be possible with many other analytical approaches.

     

Modeling temporal and spatial colony-site dynamics in a long-lived seabird

We studied the determinants of colony site dynamics in Audouin's gull, Larus audouinii, breeding in a small archipelago of the western Mediterranean. Data on island occupation were available for a series of 25 years, since first colonization of the archipelago in 1973. Group behavior was studied in relation to the components of dispersal: permanence or abandonment (extinction) on an island previously occupied and permanence or occupation (colonization) of another island. Generalized Linear Mixed Models (GLMMs) were used to identify the relative contribution of each explanatory variable to the probability of colony abandonment. Gulls showed a low probability (3%) of abandoning one of the islands (Grossa I.), especially when the colony was increasing in numbers from time t_i-1 to t_i. However, the probability of abandoning Grossa increased up to 31% when the colony was declining. The probability of island abandonment was very high for all other islands (range 66–99%) when the colony was declining, but much lower (range 36–82%) when it was increasing. Hence, we suggest that island abandonment by Audouin's gull is at least a two-step process. The first step (dispersal of a portion of the colony) probably takes place at random, as an evolutionary load typical of a species evolved in unstable habitats. The second step, a further loss of breeding pairs, seems to feedback on the first loss of members of the colony (public information), likely perceived as a loss of colony quality. Colonization of islands by gulls abandoning Grossa I. was marginally and negatively affected by the density of breeding yellow-legged gulls, a predatory species. Results apply to conservation ecology since they highlight the need to protect not only occupied patches but also those empty at present.     

Pan-Mammalian Target of Rapamycin (mTOR) Inhibitor AZD8055 Primes Rhabdomyosarcoma Cells for ABT-737-induced Apoptosis by Down-regulating Mcl-1 Protein

The PI3K/mammalian Target of Rapamycin (mTOR) pathway is often aberrantly activated in rhabdomyosarcoma (RMS) and represents a promising therapeutic target. Recent evaluation of AZD8055, an ATP-competitive mTOR inhibitor, by the Preclinical Pediatric Testing Program showed in vivo antitumor activity against childhood solid tumors, including RMS. Therefore, in the present study, we searched for AZD8055-based combination therapies. Here, we identify a new synergistic lethality of AZD8055 together with ABT-737, a BH3 mimetic that antagonizes Bcl-2, Bcl-x_L, and Bcl-w but not Mcl-1. AZD8055 and ABT-737 cooperate to induce apoptosis in alveolar and embryonal RMS cells in a highly synergistic fashion (combination index < 0.2). Synergistic induction of apoptosis by AZD8055 and ABT-737 is confirmed on the molecular level, as AZD8055 and ABT-737 cooperate to trigger loss of mitochondrial membrane potential, activation of caspases, and caspase-dependent apoptosis that is blocked by the pan-caspase inhibitor Z-VAD-fmk. Similar to AZD8055, the PI3K/mTOR inhibitor NVP-BEZ235, the PI3K inhibitor NVP-BKM120 and Akt inhibitor synergize with ABT-737 to trigger apoptosis, whereas no cooperativity is found for the mTOR complex 1 inhibitor RAD001. Interestingly, molecular studies reveal a correlation between the ability of different PI3K/mTOR inhibitors to potentiate ABT-737-induced apoptosis and to suppress Mcl-1 protein levels. Importantly, knockdown of Mcl-1 increases ABT-737-induced apoptosis similar to AZD8055/ABT-737 cotreatment. This indicates that AZD8055-mediated suppression of Mcl-1 protein plays an important role in the synergistic drug interaction. By identifying a novel synergistic interaction of AZD8055 and ABT-737, our findings have important implications for the development of molecular targeted therapies for RMS.     

Plasma N-glycome composition associates with chronic low back pain

Background

Low back pain (LBP) is the symptom of a group of syndromes with heterogeneous underlying mechanisms and molecular pathologies, making treatment selection and patient prognosis very challenging. Moreover, symptoms and prognosis of LBP are influenced by age, gender, occupation, habits, and psychological factors. LBP may be characterized by an underlying inflammatory process. Previous studies indicated a connection between inflammatory response and total plasma N-glycosylation. We wanted to identify potential changes in total plasma N-glycosylation pattern connected with chronic low back pain (CLBP), which could give an insight into the pathogenic mechanisms of the disease.

Antisense reduction of thylakoidal ascorbate peroxidase in <Emphasis Type="Italic">Arabidopsis</Emphasis> enhances Paraquat-induced photooxidative stress and Nitric Oxide-induced cell death

The production and characterization of Arabidopsis plants containing a transgene in which the Arabidopsis tAPX is inserted in antisense orientation, is described. tAPX activity in these transgenic tAPX plants is around 50% of control level. The tAPX antisense plants are phenotypically indistinguishable from control plants under normal growth conditions; they show, however, enhanced sensitivity to the O₂^–-generating herbicide, Paraquat. Interestingly, the tAPX antisense plants show enhanced symptoms of damage when cell death is triggered through treatment with the nitric oxide-donor, SNP. These results are in accordance with the ones recently obtained with transgenic plants overexpressing tAPX; altogether, they suggest that tAPX, besides the known ROS scavenging role, is also involved in the fine changes of H₂O₂ concentration during signaling events.     

Knock‐in(g) RAF for a loop

Phosphorylation of the activation loop in RAF kinases has been suggested to be critical for changes in activity. The extent to which the activation segment is phosphorylated, the specific structural consequences, and the in vivo relevance have however remained elusive. In this issue of the The EMBO Journal, Köhler et al (2015) addressed these questions by generating a knock‐in mouse expressing a B‐Raf mutant with a non‐phosphorylatable activation loop. The mutant causes a range of developmental phenotypes; intriguingly, it also impairs the tumorigenic potential of a subset of BRAF mutants, suggesting potential new strategies for RAF inhibition.     

Recipes for successful anhydrobiosis in bdelloid rotifers

We tested the effect of several environmental variables on the ability of three bdelloid rotifers (Macrotrachela quadricornifera, Philodina roseola and Adineta oculata) to recover from the anhydrobiotic state. The variables we examined were (1) rate of water evaporation, (2) relative humidity during anhydrobiosis, (3) temperature during anhydrobiosis, (4) duration of anhydrobiosis, and (5) rehydration rate. Our results indicate that bdelloids can regulate to some degree net water balance during onset and termination of anhydrobiosis.     

Enhanced Amphiphilic Profile of a Short β-Stranded Peptide Improves Its Antimicrobial Activity

SB056 is a novel semi-synthetic antimicrobial peptide with a dimeric dendrimer scaffold. Active against both Gram-negative and -positive bacteria, its mechanism has been attributed to a disruption of bacterial membranes. The branched peptide was shown to assume a β-stranded conformation in a lipidic environment. Here, we report on a rational modification of the original, empirically derived linear peptide sequence [WKKIRVRLSA-NH₂, SB056-lin]. We interchanged the first two residues [KWKIRVRLSA-NH₂, β-SB056-lin] to enhance the amphipathic profile, in the hope that a more regular β-strand would lead to a better antimicrobial performance. MIC values confirmed that an enhanced amphiphilic profile indeed significantly increases activity against both Gram-positive and -negative strains. The membrane binding affinity of both peptides, measured by tryptophan fluorescence, increased with an increasing ratio of negatively charged/zwitterionic lipids. Remarkably, β-SB056-lin showed considerable binding even to purely zwitterionic membranes, unlike the original sequence, indicating that besides electrostatic attraction also the amphipathicity of the peptide structure plays a fundamental role in binding, by stabilizing the bound state. Synchrotron radiation circular dichroism and solid-state ¹⁹F-NMR were used to characterize and compare the conformation and mobility of the membrane bound peptides. Both SB056-lin and β-SB056-lin adopt a β-stranded conformation upon binding POPC vesicles, but the former maintains an intrinsic structural disorder that also affects its aggregation tendency. Upon introducing some anionic POPG into the POPC matrix, the sequence-optimized β-SB056-lin forms well-ordered β-strands once electro-neutrality is approached, and it aggregates into more extended β-sheets as the concentration of anionic lipids in the bilayer is raised. The enhanced antimicrobial activity of the analogue correlates with the formation of these extended β-sheets, which also leads to a dramatic alteration of membrane integrity as shown by ³¹P-NMR. These findings are generally relevant for the design and optimization of other membrane-active antimicrobial peptides that can fold into amphipathic β-strands.