Jeffrey Hall

A highly adaptive commensal organism, Staphylococcus aureus, possesses an array of genes that allow the bacterium to survive and grow in a wide variety of niches. Several of these niches are known to be or become anaerobic during the course of an infection; additionally, biofilms that develop, commonly on implanted medical devices, become anaerobic. The metabolic capability of S. aureus provides the organism with the essential nutrients needed to continue to grow, divide, and thwart the host immune system in the presence or absence of oxygen. In order to utilize the ATP-producing pathways and maintain cellular health S. aureus has evolved a series of regulatory systems that regulate these ATP-producing pathways. In this review, we discuss the protein signaling systems that sense, indirectly and directly, anaerobic conditions, their sensory mechanisms and signals, and outline the genes that are altered due to the absence of oxygen and the subsequent response by the bacterial cell. The switch from aerobic to anaerobic growth in S. aureus is complex and highly regulated, with some metabolic pathways regulated by multiple regulatory systems to ensure maximal utilization of each pathway and substrate.

The reproductive biology of Drosophila melanogaster is described and critically discussed, primarily with regard to genetic studies of sex‐specific behavior and its neural underpinnings. The investigatory history of this system includes, in addition to a host of recent neurobiological analyses of reproductive phenotypes, studies of mating as well as the behaviors leading up to that event. Courtship and mating have been delved into mostly with regard to male‐specific behavior and biology, although a small number of studies has also pointed to the neural substrates of female reproduction. Sensory influences on interactions between courting flies have long been studied, partly by application of mutants and partly by surgical experiments. More recently, molecular‐genetic approaches to sensations passing between flies in reproductive contexts have aimed to “dissect” further the meaning of separate sensory modalities. Notable among these are olfactory and contact‐chemosensory stimuli, which perhaps have received an inordinate amount of attention in terms of the possibility that they could comprise the key cues involved in triggering and sustaining courtship actions. But visual and auditory stimuli are heavily involved as well—appreciated mainly from older experiments, but analyzable further using elementary approaches (single‐gene mutations mutants and surgeries), as well as by applying the molecularly defined factors alluded to above. Regarding regulation of reproductive behavior by components of Drosophila's central nervous system (CNS), once again significant invigoration of the relevant inquiries has been stimulated and propelled by identification and application of molecular‐genetic materials. A distinct plurality of the tools applied involves transposons inserted in the fly's chromosomes, defining “enhancer‐trap” strains that can be used to label various portions of the nervous system and, in parallel, disrupt their structure and function by “driving” companion transgenes predesigned for these experimental purposes. Thus, certain components of interneuronal routes, functioning along pathways whose starting points are sensory reception by the peripheral nervous system (PNS), have been manipulated to enhance appreciation of sexually important sensory modalities, as well as to promote understanding of where such inputs end up within the CNS: Where are reproductively related stimuli processed, such that different kinds of sensation would putatively be integrated to mediate sex‐specific behavioral readouts? In line with generic sensory studies that have tended to concentrate on chemical stimuli, PNS‐to‐CNS pathways focused upon in reproductive experiments relying on genic enhancers have mostly involved smell and taste. Enhancer traps have also been applied to disrupt various regions within the CNS to ask about the various ganglia, and portions thereof, that contribute to male‐ or female‐specific behavior. These manipulations have encompassed structural or functional disruptions of such regions as well as application of molecular‐genetic tricks to feminize or masculinize a given component of the CNS. Results of such experiments have, indeed, identified certain discrete subsets of centrally located ganglia that, on the one hand, lead to courtship defects when disrupted or, on the other, must apparently maintain sex‐specific identity if the requisite courtship actions are to be performed. As just implied, perturbations of certain neural tissues not based on manipulating “sex factors” might lead to reproductive behavioral abnormalities, even though changing the sexual identity of such structures would not necessarily have analogous consequences. It has been valuable to uncover these sexually significant subsets of the Drosophila nervous system, although it must be said that not all of the transgenically based dissection outcomes are in agreement. Thus, the good news is that not all of the CNS is devoted to courtship control, whereby any and all locales disrupted might have led to sex‐specific deficits; but the bad news is that the enhancer‐trap approach to these matters has not led to definitive homing‐in on some tractable number of mutually agreed‐upon “courtship centers” within the brain or within the ventral nerve cord (VNC). The latter neural region, which comprises about half of the fly's CNS, is underanalyzed as to its sex‐specific significance: How, for example, are various kinds of sensory inputs to posteriorly located PNS structures processed, such that they eventually end up modulating brain functions underlying courtship? And how are sex‐specific motor outputs mediated by discrete collections of neurons within VNC ganglia—so that, for instance, male‐specific whole‐animal motor actions and appendage usages are evoked? These behaviors can be thought of as fixed action patterns. But it is increasingly appreciated that elements of the fly's reproductive behavior can be modulated by previous experience. In this regard, the neural substrates of conditioned courtship are being more and more analyzed, principally by further usages of various transgenic types. Additionally, a set of molecular neurogenetic experiments devoted to experience‐dependent courtship was based on manipulations of a salient “sex gene” in D. melanogaster. This well‐defined factor is called fruitless (fru). The gene, its encoded products, along with their behavioral and neurobiological significance, have become objects of frenetic attention in recent years. How normal, mutated, and molecularly manipulated forms of fru seem to be generating a good deal of knowledge and insight about male‐specific courtship and mating is worthy of much attention. This previews the fact that fruitless matters are woven throughout this chapter as well as having a conspicuous section allocated to them. Finally, an acknowledgment that the reader is being subjected to lengthy preview of an article about this subject is given. This matter is mentioned because—in conjunction with the contemporary broadening and deepening of this investigatory area—brief summaries of its findings are appearing with increasing frequency. This chapter will, from time to time, present our opinion that a fair fraction of the recent minireviews are replete with too many catch phrases about what is really known. This is one reason why the treatment that follows not only attempts to describe the pertinent primary reports in detail but also pauses often to discuss our views about current understandings of sex‐specific behavior in Drosophila and its underlying biology.

This chapter discusses rhythm mutants and to a more limited extent clock molecules; including how several of the former led to examples of the latter, and how certain aspects of mutationally altered rhythms connect with studies revolving around the molecularly based control of the fly's biological oscillations. The most salient rhythm variants in Drosophila are the period mutants. The chapter concludes that one way to extend the knowledge of and insights about the circadian processes are to continue efforts in the area of pure chronogenetics: to isolate novel rhythm mutants and determine whether the genes specify suspected parts of the pacemaker machinery or whether some of the newly identified loci encode heretofore unanticipated molecular contributors. This kind of clock gene hunting, by mutations and position cloning, is how molecular chronobiology started is discussed.

This chapter discusses the genetic and molecular analysis of Drosophila behavior. The chapter reviews the recent studies in the field of genetic and molecular analysis of Drosophila behavior by using examples in which progress is made in understanding both complex and relatively simpler behavioral phenotypes. The chapter includes studies on the visual system, olfaction and contact chemoreception, learning, courtship behavior, and biological rhythms. The overlap among these systems can become evident and appears as progress through the literature. The genetic analysis of Drosophila behavior is an area that has attracted some attention over the past three decades. It is understandable perhaps that most bona fide geneticists and molecular biologists working in the area would prefer to work with much simpler phenotypes, rather than the highly complex behavioral patterns that the fly can produce. Nevertheless, their efforts are beginning to reveal some of the underlying mechanisms that determine how the nervous system functions, with obvious implications for those who are more interested in behavior.

Rhythm variations have been noticed as a result of monitoring circadian fluctuations accompanying phenotypes associated with certain insect “strains.” This chapter presents the molecular biology of Drosophila clock genes. It discusses pleiotropy of per expression, germ-line transformants, and rhythms influenced by per, informational content of the period gene, and evolutionary implications of per's structure and function. The per pleiotropy, studied by monitoring the gene's temporal and spatial expression, fits loosely with the pleiotropic effects of mutations at this locus. However, there are few explicit connections between the findings that are also summarized in the chapter. For example, per expression in the heart has apparently not been detected. Another point suggested by the localization results is that fruit flies may not have their many circadian rhythms, if there are in fact lots of themcontrolled by one “master clock.”