Animal models have been widely used to gain insight into the mechanisms underlying the acute and long-term effects of alcohol exposure. The fruit fly Drosophila melanogaster encounters ethanol in its natural habitat and possesses many adaptations that allow it to survive and thrive in ethanol-rich environments. Several assays to study ethanol-related behaviors in flies, ranging from acute intoxication to self-administration and reward, have been developed in the past 20 years. These assays have provided the basis for studying the physiological and behavioral effects of ethanol and for identifying genes mediating these effects. In this review we describe the ecological relationship between flies and ethanol, the effects of ethanol on fly development and behavior, the use of flies as a model for alcohol addiction, and the interaction between ethanol and social behavior. We discuss these advances in the context of their utility to help decipher the mechanisms underlying the diverse effects of ethanol, including those that mediate ethanol dependence and addiction in humans.

A number of aphid species produce individuals, termed soldiers, that defend the colony by attacking predators. Soldiers have either reduced or zero direct reproductive fitness. Their behavior is therefore altruistic in the classical sense: an individual is behaving in a way that incurs reproductive costs on itself and confers reproductive benefits on another. However, comparison with the better–known eusocial insects (Hymenoptera, Isoptera) indicates that there are important differences between clonal and sexual social animals.

Here we take a clone's–eye view and conclude that many facets of aphid sociality are best thought of in terms of resource allocation: for example, the choice between investment in defense and reproduction. This view considerably simplifies some aspects of the problem and highlights the qualitatively different nature of genetic heterogeneity in colonies of aphids and of other social insects. In sexually reproducing social insects, each individual usually has a different genome, which leads to genetic conflicts of interest between individuals. In social aphids, all members of a clone have identical genomes, barring new mutations, and there should be no disagreement among clonemates about investment decisions. Genetic heterogeneity within colonies can arise, but principally through clonal mixing, and this means that investment decisions will vary between different clones rather than among all individuals.

1. Defensive individuals, termed soldiers, have recently been discovered in aphids, Soldiers are typically early instar larvae, and in many species the soldiers are reproductively sterile and morphologically and behaviourally specialized. 2. Since aphids reproduce parthenogenetically, we might expect soldier production to be more widespread in aphids than it is. We suggest that a more useful way to think about these problems is to attempt to understand how a clone (rather than an individual) should invest in defence and reproduction. 3. Known soldiers are currently restricted to two families of aphids, the Pemphigidae and Hormaphididae, although they are distributed widely among genera within these families. We discuss the use of a phylogenetic perspective to aid comparative studies of soldier production and we demonstrate this approach using current estimates of phylogenetic affinities among aphids. We show that the distribution of soldier production requires a minimum of six to nine evolutionary origins plus at least one loss. 4. At least four main types of soldiers exist and we present and discuss this diversity of soldiers. 5. Most soldier-producing species produce soldiers within plant galls and we discuss the importance of galls for the evolution of soldiers. 6. We summarize the evidence on the interactions between soldiers and predators and between soldier-producing aphids and ants. 7. We present an optimality model for soldier investment strategies to help guide investigations of the ecological factors selecting for soldiers. 8. The proximate mechanisms of soldier production are currently very poorly understood and we suggest several avenues for further research.

Oncogene amplification on extrachromosomal DNA (ecDNA) is a common event, driving aggressive tumor growth, drug resistance and shorter survival. Currently, the impact of nonchromosomal oncogene inheritance-random identity by descent-is poorly understood. Also unclear is the impact of ecDNA on somatic variation and selection. Here integrating theoretical models of random segregation, unbiased image analysis, CRISPR-based ecDNA tagging with live-cell imaging and CRISPR-C, we demonstrate that random ecDNA inheritance results in extensive intratumoral ecDNA copy number heterogeneity and rapid adaptation to metabolic stress and targeted treatment. Observed ecDNAs benefit host cell survival or growth and can change within a single cell cycle. ecDNA inheritance can predict, a priori, some of the aggressive features of ecDNA-containing cancers. These properties are facilitated by the ability of ecDNA to rapidly adapt genomes in a way that is not possible through chromosomal oncogene amplification. These results show how the nonchromosomal random inheritance pattern of ecDNA contributes to poor outcomes for patients with cancer.

The extracellular matrix (ECM) regulates cell migration and sculpts organ shape. AdamTS proteins are extracellular metalloproteases known to modify ECM proteins and promote cell migration, but demonstrated roles for AdamTS proteins in regulating CNS structure and ensuring cell lineages remain fixed in place have not been uncovered. Using forward genetic approaches in Drosophila, we find that reduction of AdamTS-A function induces both the mass exodus of neural lineages out of the CNS and drastic perturbations to CNS structure. Expressed and active in surface glia, AdamTS-A acts in parallel to perlecan and in opposition to viking/collagen IV and βPS-integrin to keep CNS lineages rooted in place and to preserve the structural integrity of the CNS. viking/collagen IV and βPS-integrin are known to promote tissue stiffness and oppose the function of perlecan, which reduces tissue stiffness. Our work supports a model in which AdamTS-A anchors cells in place and preserves CNS architecture by reducing tissue stiffness.

Recent years have seen a rise in publications demonstrating coupling between transcription and mRNA decay. This coupling most often accompanies cellular processes that involve transitions in gene expression patterns, for example during mitotic division and cellular differentiation and in response to cellular stress. Transcription can affect the mRNA fate by multiple mechanisms. The most novel finding is the process of co-transcriptional imprinting of mRNAs with proteins, which in turn regulate cytoplasmic mRNA stability. Transcription therefore is not only a catalyst of mRNA synthesis but also provides a platform that enables imprinting, which coordinates between transcription and mRNA decay. Here we present an overview of the literature, which provides the evidence of coupling between transcription and decay, review the mechanisms and regulators by which the two processes are coupled, discuss why such coupling is beneficial and present a new model for regulation of gene expression. This article is part of a Special Issue entitled: RNA Decay mechanisms.

The brain's synaptic networks endow an animal with powerfully adaptive biological behavior. Maps of such synaptic circuits densely reconstructed in those model brains, which can be examined and manipulated by genetic means, offer the best prospect for understanding the underlying biological bases of behavior. That prospect is now technologically feasible and a scientifically enabling possibility in neurobiology, much as genomics has been in molecular biology and genetics. In , two major advances are in electron microscopic technology, using focused ion beam-scanning electron microscopy (FIB-SEM) milling to capture and align digital images, and in computer-aided reconstruction of neuron morphologies. The last decade has witnessed enormous progress in detailed knowledge of the actual synaptic circuits formed by real neurons. Advances in various brain regions that heralded identification of the motion-sensing circuits in the optic lobe are now extending to other brain regions, with the prospect of encompassing the fly's entire nervous system, both brain and ventral nerve cord. Expected final online publication date for the Volume 35 is October 7, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Any method for RNA secondary structure prediction is determined by four ingredients. The architecture is the choice of features implemented by the model (such as stacked basepairs, loop length distributions, etc.). The architecture determines the number of parameters in the model. The scoring scheme is the nature of those parameters (whether thermodynamic, probabilistic, or weights). The parameterization stands for the specific values assigned to the parameters. These three ingredients are referred to as "the model." The fourth ingredient is the folding algorithms used to predict plausible secondary structures given the model and the sequence of a structural RNA. Here, I make several unifying observations drawn from looking at more than 40 years of methods for RNA secondary structure prediction in the light of this classification. As a final observation, there seems to be a performance ceiling that affects all methods with complex architectures, a ceiling that impacts all scoring schemes with remarkable similarity. This suggests that modeling RNA secondary structure by using intrinsic sequence-based plausible "foldability" will require the incorporation of other forms of information in order to constrain the folding space and to improve prediction accuracy. This could give an advantage to probabilistic scoring systems since a probabilistic framework is a natural platform to incorporate different sources of information into one single inference problem.

Alterations in Hox gene expression patterns have been implicated in both large and small-scale morphological evolution. An improved understanding of these changes requires a detailed understanding of Hox gene cis-regulatory function and evolution. cis-regulatory evolution of the Hox gene Ultrabithorax (Ubx) has been shown to contribute to evolution of trichome patterns on the posterior second femur (T2p) of Drosophila species. As a step toward determining how this function of Ubx has evolved, we performed a series of experiments to clarify the role of Ubx in patterning femurs and to identify the cis-regulatory regions of Ubx that drive expression in T2p. We first performed clonal analysis to further define Ubx function in patterning bristle and trichome patterns in the legs. We found that low levels of Ubx expression are sufficient to repress an eighth bristle row on the posterior second and third femurs, whereas higher levels of expression are required to promote the development and migration of other bristles on the third femur and to repress trichomes. We then tested the hypothesis that the evolutionary difference in T2p trichome patterns due to Ubx was caused by a change in the global cis-regulation of Ubx expression. We found no evidence to support this view, suggesting that the evolved difference in Ubx function reflects evolution of a leg-specific enhancer. We then searched for the regulatory regions of the Ubx locus that drive expression in the second and third femur by assaying all existing regulatory mutations of the Ubx locus and new deficiencies in the large intron of Ubx that we generated by P-element-induced male recombination. We found that two enhancer regions previously known to regulate Ubx expression in the legs, abx and pbx, are required for Ubx expression in the third femur, but that they do not contribute to pupal expression of Ubx in the second femur. This analysis allowed us to rule out at least 100 kb of DNA in and around the Ubx locus as containing a T2p-specific enhancer. We then surveyed an additional approximately 30 kb using enhancer constructs. None of these enhancer constructs produced an expression pattern similar to Ubx expression in T2p. Thus, after surveying over 95% of the Ubx locus, we have not been able to localize a T2p-specific enhancer. While the enhancer could reside within the small regions we have not surveyed, it is also possible that the enhancer is structurally complex and/or acts only within its native genomic context.

The primary auditory cortex (A1) is organized tonotopically, with neurons sensitive to high and low frequencies arranged in a rostro-caudal gradient. We used laser scanning photostimulation in acute slices to study the organization of local excitatory connections onto layers 2 and 3 (L2/3) of the mouse A1. Consistent with the organization of other cortical regions, synaptic inputs along the isofrequency axis (orthogonal to the tonotopic axis) arose predominantly within a column. By contrast, we found that local connections along the tonotopic axis differed from those along the isofrequency axis: some input pathways to L3 (but not L2) arose predominantly out-of-column. In vivo cell-attached recordings revealed differences between the sound-responsiveness of neurons in L2 and L3. Our results are consistent with the hypothesis that auditory cortical microcircuitry is specialized to the one-dimensional representation of frequency in the auditory cortex.