Evidence for the antiquity and importance of microbial pathogens as selective agents is found in the proliferation of antimicrobial defences throughout the animal kingdom. Social insects, typified by crowding and often by low genetic variation, have high probabilities of disease transmission and eusocial Hymenoptera may be particularly vulnerable because of haplodiploidy. Mechanisms they employ to reduce the risk of disease include antimicrobial secretions which are particularly important primary barriers to infection. However, until now, whether or not there is selection for stronger antimicrobial secretions when the risk of disease increases because of sociality has not been tested. Here, we present evidence that the production of progressively stronger antimicrobial compounds was critical to the evolution of sociality in bees. We found that increases in group size and genetic relatedness were strongly correlated with increasing antimicrobial strength. The antimicrobials of even the most primitive semi-social species were an order of magnitude stronger that those of solitary species, suggesting a point of no return, beyond which disease control was essential. Our results suggest that selection by microbial pathogens was critical to the evolution of sociality and required the production of strong, front-line antimicrobial defences.

NF-κB plays an important role in cancer initiation and progression. CD44, a cell surface glycoprotein, is involved in many cellular processes including cell adhesion, migration and proliferation. However, whether and how the two molecules interact in breast cancer is not clear. In recent years, the up-regulation of CD44 has served as a marker for tumor initiating cells in breast cancer and other cancer types. Despite the important role of CD44 in cellular processes and cancer, the mechanism underlying CD44 up-regulation in cancers remains poorly understood. Previously, we have identified a novel cis-element, CR1, located upstream of the CD44 promoter. We demonstrated that NF-κB and AP-1 are key trans-acting factors that interact with CR1. Here, we further analyzed the role of NF-κB in regulating CD44 expression in triple negative breast cancer cells, MDA-MB-231 and SUM159. Inhibition of NF-κB by Bay-11-7082 resulted in a reduction in CD44 expression. CD44 repression via NF-κB inhibition consequently decreased proliferation and invasiveness of breast cancer cells. These findings provide not only new insight into the molecular mechanism underlying CD44 regulation but also potential therapeutic targets that may help eliminate chemo- and radiation-resistant cancer cells.

We hypothesize that aggregations of animals are likely to attract pathogenic micro-organisms and that this is especially the case for semisocial and eusocial insects where selection ultimately led to group sizes in the thousands or even millions, attracting the epithet ‘superorganism’. Here, we analyse antimicrobial strength, per individual, in eight thrips species (Insecta: Thysanoptera) that present increasing innate group sizes and show that species with the largest group size (100–700) had the strongest antimicrobials, those with smaller groups (10–80) had lower antimicrobial activity, while solitary species showed none. Species with large innate group sizes showed strong antimicrobial activity while the semisocial species showed no activity until group size increased sufficiently to make activity detectable. The eusocial species behaved in a similar way, with detectable activity appearing once group size exceeded 120. These analyses show that antimicrobial strength is determined by innate group size. This suggests that the evolution of sociality that, by definition, increases group size, may have had particular requirements for defences against microbial pathogens. Thus, increase in group size, accompanied by increased antibiotic strength, may have been a critical factor determining the ‘point of no return’, early in the evolution of social insects, beyond which the evolution of social anatomical and morphological traits was irreversible. Our data suggest that traits that increase group size in general are accompanied by increased antimicrobial strength and that this was critical for transitions from solitary to social and eusocial organization.

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Breast cancers contain a heterogeneous population of cells with a small percentage that possess properties similar to those found in stem cells. One of the widely accepted markers of breast cancer stem cells (BCSCs) is the cell surface marker CD44. As a glycoprotein, CD44 is involved in many cellular processes including cell adhesion, migration and proliferation, making it pro-oncogenic by nature. CD44 expression is highly up-regulated in BCSCs, and has been implicated in tumorigenesis and metastasis. However, the genetic mechanism that leads to a high level of CD44 expression in breast cancer cells and BCSCs is not well understood. Here, we identify a novel cis-element of the CD44 directs gene expression in breast cancer cells in a cell type specific manner. We have further identified key trans-acting factor binding sites and nuclear factors AP-1 and NFκB that are involved in the regulation of cell-specific CD44 expression. These findings provide new insight into the complex regulatory mechanism of CD44 expression, which may help identify more effective therapeutic targets against the breast cancer stem cells and metastatic tumors.

Interneurons comprise approximately one third of the total cortical neurons in the mammalian cerebral cortex. Studies have revealed many details in the generation of this cell type. However, the mechanism that defines interneuron-lineage specific gene expression is not well understood. Gene regulatory elements, e.g., promoters, enhancers, and trans-acting factors, are essential for the proper control of gene expression. Here, we report that a novel evolutionarily conserved cis-element in the second intron of the Notch1 locus play an important role in regulating gene expression in interneuron progenitors. The spatiotemporal activity of the cis-element in the developing central nervous system (CNS) was determined by both transient reporter expression in the developing chick and a transgenic mouse model. Its activity is well correlated with neurogenesis in both the chick and mouse and restricted to neural progenitor cells in the ganglionic eminence that are fated to differentiate into GABAergic interneurons of the neocortex. We further demonstrate that the cis-element activity requires the binding motif for trans-acting factors Gsh1/Barx2/Brn3. Deletion of this binding motif abolishes reporter gene expression. Together, these data provide new insights into the regulatory mechanisms of interneuron development in the vertebrate CNS.

In the hymenopterans, haplodiploidy, leading to high-genetic relatedness amongst full sisters has been regarded as critical to kin selection and inclusive fitness hypotheses that explain the evolution of eusociality and altruistic behaviours. Recent evidence for independent origins of eusociality in phylogenetically diverse taxa has led to the controversy regarding the general importance of relatedness to eusociality and its evolution. Here, we developed a highly polymorphic microsatellite marker to test whether the eusocial ambrosia beetle Austroplatypus incompertus (Schedl) is haplodiploid or diplodiploid. We found that both males and females of A. incompertus are diploid, signifying that altruistic behaviour resulting from relatedness asymmetries did not play a role in the evolution of eusocialty in this species. This provides additional evidence against the haplodiploidy hypothesis and implicates alternative hypotheses for the evolution of eusociality.

The lifetime monogamy hypothesis claims that the evolution of permanently unmated worker castes always requires maximal full-sibling relatedness to be established first. The long-lived diploid ambrosia beetle Austroplatypus incompertus (Schedl) is known to be highly social, but whether it has lifetime sterile castes has remained unclear. Here we show that the gallery systems of this beetle inside the heartwood of live Eucalyptus trees are always inhabited by a single core family, consisting of a lifetime-inseminated mother, permanently unmated daughter workers, and immatures that are always full siblings to each other and their adult caretakers. Overall sex ratios are even. Males always disperse and only survive as stored sperm, but female offspring either disperse to mate and found their own colony or assume unmated worker roles, probably surviving for many years without any reproductive potential because tarsal loss precludes later dispersal. A well-supported Platypodinae phylogeny has allowed us to infer that parental monogamy evolved before a lifetime-unmated worker caste emerged, confirming the prediction that monogamy and full-sibling relatedness are necessary conditions for the evolution of such workers. The initially very challenging but ultimately long-term stable nesting habitat in live trees appears to have provided the crucial benefit/cost factor for maintaining selection for permanently sterile workers after strict monogamy and lifetime sperm storage had become established in this curculionid coleopteran lineage.