Differences in Olfactory Discrimination, but Not Sensitivity, Between African Savanna and Asian Elephants.

While African savanna and Asian elephants split between 4.2 and 9 MYA, they are often regarded as one united group, 'elephants.' This is surprising because, while both are keystone species in their respective habitats, each faces different environmental pressures and has rarely been compared experimentally.

Investigating intentionality in elephant gestural communication.

A crucial feature of language is the ability to communicate cognitive goals to a specific audience, i.e. goal-directed intentionality.

Wild elephants vary in their attraction to novelty across an anthropogenic landscape gradient.

Research on how wild animals respond to novelty is becoming more relevant as the overlap between natural habitats and human-dominated landscapes increases. Wild Asian elephants spend more time in anthropogenic landscapes as their habitat is converted to agriculture. Greater neophilia and exploration may allow elephants to successfully access agricultural resources, which may cause negative interactions with people.

Knowledge transmission, culture and the consequences of social disruption in wild elephants.

Cultural knowledge is widely presumed to be important for elephants. In all three elephant species, individuals tend to congregate around older conspecifics, creating opportunities for social transmission. However, direct evidence of social learning and cultural traditions in elephants is scarce.

A special issue in honor of the contributions of Professor Nicola S. Clayton FRS.

It has been an honor to edit this special issue of Learning & Behavior to recognize the exceptional contributions of Prof. Nicky S. Clayton FRS to the fields of comparative cognition and developmental and experimental psychology.

Synthetic lethality of mRNA quality control complexes in cancer.

Synthetic lethality exploits the genetic vulnerabilities of cancer cells to enable a targeted, precision approach to treat cancer. Over the past 15 years, synthetic lethal cancer target discovery approaches have led to clinical successes of PARP inhibitors and ushered several next-generation therapeutic targets such as WRN, USP1, PKMYT1, POLQ and PRMT5 into the clinic. Here we identify, in human cancer, a novel synthetic lethal interaction between the PELO-HBS1L and SKI complexes of the mRNA quality control pathway.

Do elephants really never forget? What we know about elephant memory and a call for further investigation.

Despite popular culture's promotion of the elephant's ability to "never forget," there is remarkably limited empirical research on the memory capacities of any living elephant species (Asian, Elephas maximus; African savanna, Loxodonta africana; African forest, Loxodonta cyclotis). A growing body of literature on elephant cognition and behavioral ecology has provided insight into the elephant's ability to behave flexibly in changing physical and social environments, but little direct evidence of how memory might relate to this flexibility exists. In this paper, we review and discuss the potential relationships between what we know about elephant cognition and behavior and the elephants' memory for the world around them as they navigate their physical, social, and spatial environments.

MYC Family Amplification Dictates Sensitivity to BET Bromodomain Protein Inhibitor Mivebresib (ABBV075) in Small-Cell Lung Cancer.

Small-cell lung cancer (SCLC) accounts for nearly 15% of all lung cancers. Although patients respond to first-line therapy readily, rapid relapse is inevitable, with few treatment options in the second-line setting. Here, we describe SCLC cell lines harboring amplification of MYC and MYCN but not MYCL1 or non-amplified MYC cell lines exhibit superior sensitivity to treatment with the pan-BET bromodomain protein inhibitor mivebresib (ABBV075).

Inhibition of MALT1 and BCL2 Induces Synergistic Antitumor Activity in Models of B-Cell Lymphoma.

The activated B cell (ABC) subset of diffuse large B-cell lymphoma (DLBCL) is characterized by chronic B-cell receptor signaling and associated with poor outcomes when treated with standard therapy. In ABC-DLBCL, MALT1 is a core enzyme that is constitutively activated by stimulation of the B-cell receptor or gain-of-function mutations in upstream components of the signaling pathway, making it an attractive therapeutic target. We discovered a novel small-molecule inhibitor, ABBV-MALT1, that potently shuts down B-cell signaling selectively in ABC-DLBCL preclinical models leading to potent cell growth and xenograft inhibition.

The endangered brain: actively preserving animal behaviour and cognition will benefit conservation.

Endangered species have small, unsustainable population sizes that are geographically or genetically restricted. conservation programmes are therefore faced with the challenge of breeding sufficiently sized, genetically diverse populations earmarked for reintroduction that have the behavioural skills to survive and breed in the wild. Yet, maintaining historically beneficial behaviours may be insufficient, as research continues to suggest that certain cognitive-behavioural skills and flexibility are necessary to cope with human-induced rapid environmental change (HIREC).

Elephants as an animal model for self-domestication.

Humans are unique in their sophisticated culture and societal structures, their complex languages, and their extensive tool use. According to the human self-domestication hypothesis, this unique set of traits may be the result of an evolutionary process of self-induced domestication, in which humans evolved to be less aggressive and more cooperative. However, the only other species that has been argued to be self-domesticated besides humans so far is bonobos, resulting in a narrow scope for investigating this theory limited to the primate order.

Day and night camera trap videos are effective for identifying individual wild Asian elephants.

Regular monitoring of wild animal populations through the collection of behavioral and demographic data is critical for the conservation of endangered species. Identifying individual Asian elephants (), for example, can contribute to our understanding of their social dynamics and foraging behavior, as well as to human-elephant conflict mitigation strategies that account for the behavior of specific individuals involved in the conflict. Wild elephants can be distinguished using a variety of different morphological traits-.

Acknowledging the Relevance of Elephant Sensory Perception to Human-Elephant Conflict Mitigation.

Elephants are well known for their socio-cognitive abilities and capacity for multi-modal sensory perception and communication. Their highly developed olfactory and acoustic senses provide them with a unique non-visual perspective of their physical and social worlds. The use of these complex sensory signals is important not only for communication between conspecifics, but also for decisions about foraging and navigation.

Persistence is key: investigating innovative problem solving by Asian elephants using a novel multi-access box.

Innovative problem solving is considered a hallmark measure of behavioral flexibility as it describes behavior by which an animal manipulates its environment in a novel way to reach a goal. Elephants are a highly social taxa that have demonstrated a remarkable capacity for adapting to changing environments. To understand how individual differences in behavior impact expressions of innovation, we used a novel extractive foraging device comprised of three compartments to evaluate innovation in 14 captive Asian elephants.

Cooperating elephants mitigate competition until the stakes get too high.

Cooperation is ubiquitous in the animal kingdom as it aims to maximize benefits through joint action. Selection, however, may also favor competitive behaviors that could violate cooperation. How animals mitigate competition is hotly debated, with particular interest in primates and little attention paid thus far to nonprimates.

Selective Inhibition of the Second Bromodomain of BET Family Proteins Results in Robust Antitumor Activity in Preclinical Models of Acute Myeloid Leukemia.

Dual bromodomain BET inhibitors that bind with similar affinities to the first and second bromodomains across BRD2, BRD3, BRD4, and BRDT have displayed modest activity as monotherapy in clinical trials. Thrombocytopenia, closely followed by symptoms characteristic of gastrointestinal toxicity, have presented as dose-limiting adverse events that may have prevented escalation to higher dose levels required for more robust efficacy. ABBV-744 is a highly selective inhibitor for the second bromodomain of the four BET family proteins.

Toll-like receptor 4 signaling activates ERG function in prostate cancer and provides a therapeutic target.

The gene fusion and subsequent overexpression of the ERG transcription factor occurs in ∼50% of prostate tumors, making it the most common abnormality of the prostate cancer genome. While ERG has been shown to drive tumor progression and cancer-related phenotypes, as a transcription factor it is difficult to target therapeutically. Using a genetic screen, we identified the toll-like receptor 4 (TLR4) signaling pathway as important for ERG function in prostate cells.

Investigating Indirect and Direct Reputation Formation in Asian Elephants ().

Reputation is a key component in social interactions of group-living animals and appears to play a role in the establishment of cooperation. Animals can form a reputation of an individual by directly interacting with them or by observing them interact with a third party, i.e.

Investigating the use of sensory information to detect and track prey by the Sunda pangolin (Manis javanica) with conservation in mind.

Pangolins are of conservation concern as one of the most heavily poached, yet least understood mammals. The Sunda pangolin (Manis javanica) in particular is a critically endangered species. Here, we investigate the behaviour of these pangolins, for the first time, using a battery of cognitive tasks based on a manipulation of available sensory information.

Selective inhibition of the BD2 bromodomain of BET proteins in prostate cancer.

Proteins of the bromodomain and extra-terminal (BET) domain family are epigenetic readers that bind acetylated histones through their bromodomains to regulate gene transcription. Dual-bromodomain BET inhibitors (DbBi) that bind with similar affinities to the first (BD1) and second (BD2) bromodomains of BRD2, BRD3, BRD4 and BRDt have displayed modest clinical activity in monotherapy cancer trials. A reduced number of thrombocytes in the blood (thrombocytopenia) as well as symptoms of gastrointestinal toxicity are dose-limiting adverse events for some types of DbBi.

The use of a human's location and social cues by Asian elephants in an object-choice task.

Asian elephants have previously demonstrated an ability to follow olfactory cues, but not human-provided social cues like pointing and gazing or orienting to find hidden food (Plotnik et al. in PLoS One 8:e61174, 2013; Anim Behav 88:91-98, 2014). In a study conducted with African elephants, however, elephants were able to follow a combination of these social cues to find food, even when the experimenter's position was counter to the location of the food.

Elephants have a nose for quantity.

Animals often face situations that require making decisions based on quantity. Many species, including humans, rely on an ability to differentiate between more and less to make judgments about social relationships, territories, and food. Habitat-related choices require animals to decide between areas with greater and lesser quantities of food while also weighing relative risk of danger based on group size and predation risk.

ETS1 induction by the microenvironment promotes ovarian cancer metastasis through focal adhesion kinase.

Metastatic colonization involves paracrine/juxtacrine interactions with the microenvironment inducing an adaptive response through transcriptional regulation. However, the identities of transcription factors (TFs) induced by the metastatic microenvironment in ovarian cancer (OC) and their mechanism of action is poorly understood. Using an organotypic 3D culture model recapitulating the early events of metastasis, we identified ETS1 as the most upregulated member of the ETS family of TFs in metastasizing OC cells as they interacted with the microenvironment.