EV20, a Novel Anti-ErbB-3 Humanized Antibody,Promotes ErbB-3 Down-Regulation and Inhibits Tumor Growth In Vivo

ErbB-3 (HER-3) receptor is involved in tumor progression and resistance to therapy. Development of specific inhibitors impairing the activity of ErbB-3 is an attractive tool for cancer therapeutics. MP-RM-1, a murine monoclonal antibody targeting human ErbB-3, has shown anticancer activity in preclinical models. With the aim to provide novel candidates for clinical use, we have successfully generated a humanized version of MP-RM-1. The humanized antibody, named EV20, abrogates both ligand-dependent and ligand-independent receptor signaling of several tumor cell types, strongly promotes ErbB-3 down-regulation, and efficiently and rapidly internalizes into tumor cells. Furthermore, treatment with EV20 significantly inhibits growth of xenografts originating from prostatic, ovarian, and pancreatic cancers as well as melanoma in nude mice. In conclusion, we provide a novel candidate for ErbB-3-targeted cancer therapy.     

Identification of Annexin A1 interacting proteins in chronic myeloid leukemia KCL22 cells

In the present study, we used a functional proteomic approach to identify Annexin A1 (Anxa1) interacting proteins in the Philadelphia‐positive KCL22 cell line. We focused on Anxa1 because it is one of the major proteins upregulated in imatinib‐sensitive KCL22S cells versus imatinib‐resistant KCL22R. Our proteomic strategy revealed 21 interactors. Bioinformatic analysis showed that most of these proteins are involved in cell death processes. Among the proteins identified, we studied the interaction of Anxa1 with two phosphatases, Shp1 and Shp2, which were recently identified as biomarkers of imatinib sensitivity in patients affected by chronic myeloid leukemia. Our data open new perspectives in the search for annexin‐mediated signaling pathways and may shed light on mechanisms of resistance to imatinib that are unrelated to Bcr‐Abl activity. All mass spectrometry data have been deposited in the ProteomeXchange with identifier PXD000030.     

Habitat use of coexisting introduced eastern cottontail and native European hare

The niche of introduced species and that of native ones may overlap, thus causing detrimental effects on the latter through competitive interactions. We used radio telemetry to investigate habitat partitioning during the active period by the introduced American eastern cottontail (Sylvilagus floridanus) and the native European hare (Lepus europaeus) in sympatric conditions. Home ranges of cottontails varied from 1.1–2.2 ha in autumn to 3.0–3.6 ha in summer. In hares, home ranges were 30.5–33.8 ha in summer and increased to 49.5–85.9 ha in winter. Both species used an overall area composed of about 27% of natural habitats (i.e., meadows, woodlands, shrubby habitats, shores, and uncultivated land) and over 70% of field crops. The coexistence of the two species appeared to be facilitated by habitat partitioning. Habitat use of cottontails was characterized by a preference for natural habitats at the study area level as well as within the home ranges, while hares showed a preference for crop fields at both spatial scales and a seasonal selection of meadows within home ranges. Habitat overlap measured with the Pianka index was 0.57–0.64 in autumn and winter, and increased in summer and spring to 0.73–0.78. Our results provide evidence of different resource selection strategies adopted by these two sympatric lagomorph species. Hare populations are often found in agricultural landscapes at low-densities, while cottontails are currently spreading throughout Northern Italy to such an extent that an eradication programme appears unfeasible. In this situation, conservation measures for hares and other species should also take into consideration the presence or possible arrival of cottontails. Habitat restoration measures that would increase the amount of fallow lands and shrublands may favour cottontails more than hares. In areas where introduced lagomorphs are present, the necessity of natural open landscapes for hares may be better faced by increasing the presence of meadows, that are seasonally used by hares and not by cottontails.     

Comprehensive Genetic Dissection of the Hemocyte Immune Response in the Malaria Mosquito Anopheles gambiae

Reverse genetics in the mosquito Anopheles gambiae by RNAi mediated gene silencing has led in recent years to an advanced understanding of the mosquito immune response against infections with bacteria and malaria parasites. We developed RNAi screens in An. gambiae hemocyte-like cells using a library of double-stranded RNAs targeting 109 genes expressed highly or specifically in mosquito hemocytes to identify novel regulators of the hemocyte immune response. Assays included phagocytosis of bacterial bioparticles, expression of the antimicrobial peptide CEC1, and basal and induced expression of the mosquito complement factor LRIM1. A cell viability screen was also carried out to assess dsRNA cytotoxicity and to identify genes involved in cell growth and survival. Our results identify 22 novel immune regulators, including proteins putatively involved in phagosome assembly and maturation (Ca²⁺ channel, v-ATPase and cyclin-dependent protein kinase), pattern recognition (fibrinogen-domain lectins and Nimrod), immune modulation (peptidase and serine protease homolog), immune signaling (Eiger and LPS-induced factor), cell adhesion and communication (Laminin B1 and Ninjurin) and immune homeostasis (Lipophorin receptor). The development of robust functional cell-based assays paves the way for genome-wide functional screens to study the mosquito immune response to infections with human pathogens.     

Visual Cues Given by Humans Are Not Sufficient for Asian Elephants (Elephas maximus) to Find Hidden Food

Recent research suggests that domesticated species – due to artificial selection by humans for specific, preferred behavioral traits – are better than wild animals at responding to visual cues given by humans about the location of hidden food. \Although this seems to be supported by studies on a range of domesticated (including dogs, goats and horses) and wild (including wolves and chimpanzees) animals, there is also evidence that exposure to humans positively influences the ability of both wild and domesticated animals to follow these same cues. Here, we test the performance of Asian elephants (Elephas maximus) on an object choice task that provides them with visual-only cues given by humans about the location of hidden food. Captive elephants are interesting candidates for investigating how both domestication and human exposure may impact cue-following as they represent a non-domesticated species with almost constant human interaction. As a group, the elephants (n = 7) in our study were unable to follow pointing, body orientation or a combination of both as honest signals of food location. They were, however, able to follow vocal commands with which they were already familiar in a novel context, suggesting the elephants are able to follow cues if they are sufficiently salient. Although the elephants’ inability to follow the visual cues provides partial support for the domestication hypothesis, an alternative explanation is that elephants may rely more heavily on other sensory modalities, specifically olfaction and audition. Further research will be needed to rule out this alternative explanation.     

Early and Middle Holocene Hunter-Gatherer Occupations in Western Amazonia: The Hidden Shell Middens

We report on previously unknown early archaeological sites in the Bolivian lowlands, demonstrating for the first time early and middle Holocene human presence in western Amazonia. Multidisciplinary research in forest islands situated in seasonally-inundated savannahs has revealed stratified shell middens produced by human foragers as early as 10,000 years ago, making them the oldest archaeological sites in the region. The absence of stone resources and partial burial by recent alluvial sediments has meant that these kinds of deposits have, until now, remained unidentified. We conducted core sampling, archaeological excavations and an interdisciplinary study of the stratigraphy and recovered materials from three shell midden mounds. Based on multiple lines of evidence, including radiocarbon dating, sedimentary proxies (elements, steroids and black carbon), micromorphology and faunal analysis, we demonstrate the anthropogenic origin and antiquity of these sites. In a tropical and geomorphologically active landscape often considered challenging both for early human occupation and for the preservation of hunter-gatherer sites, the newly discovered shell middens provide evidence for early to middle Holocene occupation and illustrate the potential for identifying and interpreting early open-air archaeological sites in western Amazonia. The existence of early hunter-gatherer sites in the Bolivian lowlands sheds new light on the region’s past and offers a new context within which the late Holocene “Earthmovers” of the Llanos de Moxos could have emerged.     

Factors influencing the diurnal behaviour of white rhino (Ceratotherium simum) in Matobo National Park,Zimbabwe

Activity periods and diurnal behaviour of southern white rhino (Ceratotherium simum simum) were studied in Matobo National Park, Zimbabwe, from August 2016 to July 2017 using camera trapping and focal group sampling, respectively. Camera trap data showed that diurnal and nocturnal movements of white rhino varied significantly with moon phase, with more frequent nocturnal photographic captures during full- and third-quarter moon phases than during new and crescent moon phases. Permutational MANOVA and canonical correspondence analysis of focal group observation data were used to test the effects of season, time of day, habitat type, distance to roads, moon phase, presence/absence of other mammals, age/sex category, individual identity and herd composition on daytime behaviour. Weather conditions accounted for the majority of variation in rhino behaviour, with more time spent feeding during cloudy and rainy weather than sunny weather. Time of day and moon phase also accounted for high variation in behaviour, followed by habitat attributes and age/sex category. Variance partitioning by sets of explanatory variables showed that weather conditions had the greatest explanatory power in the variation of rhino behaviour, followed by temporal attributes, habitat attributes and age/sex category. Our findings provide insights for white rhino population management strategies aimed at increasing the effectiveness of security patrols, minimising disturbance and improving sightings for tourists.