Friends and Foes from an Ant Brain's Point of View – Neuronal Correlates of Colony Odors in a Social Insect

Background: Successful cooperation depends on reliable identification of friends and foes. Social insects discriminate colony members (nestmates/friends) from foreign workers (non-nestmates/foes) by colony-specific, multi-component colony odors. Traditionally, complex processing in the brain has been regarded as crucial for colony recognition. Odor information is represented as spatial patterns of activity and processed in the primary olfactory neuropile, the antennal lobe (AL) of insects, which is analogous to the vertebrate olfactory bulb. Correlative evidence indicates that the spatial activity patterns reflect odor-quality, i.e., how an odor is perceived. For colony odors, alternatively, a sensory filter in the peripheral nervous system was suggested, causing specific anosmia to nestmate colony odors. Here, we investigate neuronal correlates of colony odors in the brain of a social insect to directly test whether they are anosmic to nestmate colony odors and whether spatial activity patterns in the AL can predict how odor qualities like ‘‘friend’’ and ‘‘foe’’ are attributed to colony odors. Methodology/Principal Findings: Using ant dummies that mimic natural conditions, we presented colony odors and investigated their neuronal representation in the ant Camponotus floridanus. Nestmate and non-nestmate colony odors elicited neuronal activity: In the periphery, we recorded sensory responses of olfactory receptor neurons (electroantennography), and in the brain, we measured colony odor specific spatial activity patterns in the AL (calcium imaging). Surprisingly, upon repeated stimulation with the same colony odor, spatial activity patterns were variable, and as variable as activity patterns elicited by different colony odors. Conclusions: Ants are not anosmic to nestmate colony odors. However, spatial activity patterns in the AL alone do not provide sufficient information for colony odor discrimination and this finding challenges the current notion of how odor quality is coded. Our result illustrates the enormous challenge for the nervous system to classify multi-component odors and indicates that other neuronal parameters, e.g., precise timing of neuronal activity, are likely necessary for attribution of odor quality to multi-component odors

ORIGINAL ARTICLE Seasonal nestmate recognition in the ant Formica exsecta

Abstract Under favorable conditions, the mound-building ant Formica exsecta may form polydomous colonies and can establish large nest aggregations. The lack of worker aggression towards nonnestmate conspecifics is a typical behavioral feature in such social organization, allowing for a free flux of individuals among nests. However, this mutual worker toleration may vary over the seasons and on spatial scales. We studied spatio-temporal variation of worker–worker aggression within and among nests of a polydomous F. exsecta population. In addition, we determined inter- and intracolony genetic relatedness by microsatellite DNA genotyping and assessed its effect on Communicated by J. Heinz

ABR, a novel inducer of transcription factor C/EBPα, contributes to myeloid differentiation and is a favorable prognostic factor in acute myeloid leukemia

Active BCR related (ABR) gene deactivates ras-related C3 botulinum toxin substrate 1 (RAC1), which plays an essential role in regulating normal hematopoiesis and in leukemia. BCR gene, closely related to ABR, acts as a tumor suppressor in chronic myeloid leukemia and has overlapping functions with ABR. Evidence for a putative tumor suppressor role of ABR has been shown in several solid tumors, in which deletion of ABR is present. Our results show downregulation of ABR in AML. A block of ABR prevents myeloid differentiation and leads to repression of the myeloid transcription factor C/EBPα, a major regulator of myeloid differentiation and functionally impaired in leukemia. Conversely, stable overexpression of ABR enhances myeloid differentiation. Inactivation of the known ABR target RAC1 by treatment with the RAC1 inhibitor NSC23766 resulted in an increased expression of C/EBPα in primary AML samples and in AML cell lines U937 and MV4;11. Finally, AML patients with high ABR expression at diagnosis showed a significant longer overall survival and patients who respond to azacitidine therapy showed a significant higher ABR expression. This is the first report showing that ABR expression plays a critical role in both myelopoiesis and AML. Our data indicate the tumor suppressor potential of ABR and underline its potential role in leukemia therapeutic strategies

Disruption of the C/EBP? - MiR-182 balance impairs granulocytic differentiation

10.1038/s41467-017-00032-6Nature Communications813

Disturbance of the C/EBP alpha-miR-182 balance impairs granulocytic differentiation and promotes development of acute myeloid leukemia

Introduction: Silencing of major myeloid transcription factor C/EBPa by gene mutation, promoter hypermethylation or posttranslational modifications is well described and occurs in ~50% of acute myeloid leukemia (AML) cases. Deregulation of C/EBPa by microRNAs, a class of small non-coding RNAs, as a substantial event during AML development or during myeloid differentiation has not been studied yet. Methods: We screened for C/EBPa dependent miRNAs in inducible K562-C/EBPa-ER cells using Illumina’s Next Generation Sequencing. For in vitro functional studies including gain-of-function and loss-of-function experiments, we utilized common acute myeloid leukemia cell lines, human hematopoietic stem cells from umbilical cord blood, murine hematopoietic stem cells from mouse bone marrow and primary human cells from patients with acute myeloid leukemia. For in vivo investigations, we manipulated Lin-Sca-1+c-Kit+ (LSK) murine hematopoietic progenitor cells by lentiviral infection and transplanted them into lethally irradiated littermates. The resulting phenotype was analyzed by flow cytometry and morphological staining of blood and bone marrow. Results: We identified oncogenic miR-182 as strong regulator of C/EBPa during myeloid differentiation and in AML. Moreover, we uncovered a novel regulatory loop between C/EBPa and miR-182. While C/EBPa blocks miR-182 expression by direct promoter binding during myeloid differentiation, enforced expression of miR-182 leads to reduced C/EBPa protein levels and impairs granulopoiesis in vitro and in a transplantation based mouse model in vivo. In contrast to this, a knockdown of miR-182 expression enhances C/EBPa protein levels in human AML. Furthermore, we observed highly elevated miR-182 expression levels particularly in AML patients with C-terminal CEBPA mutations and thereby uncovered a mechanism how C/EBPa blocks miR-182 expression. Finally by evaluation of TCGA database, we identified miR-182 expression as a strong adverse prognostic factor in cytogenetically high risk AML patients. Conclusions: Taken together, our data demonstrate the importance of a controlled balance between C/EBPa and miR-182 for the maintenance of healthy granulopoiesis and might uncover a novel mechanism for potential treatment strategies in AML. Disclosure: No conflict of interest disclosed