Masculinized Drosophila females adapt their fighting strategies to their opponent.

Many animal species show aggression to gain mating partners and to protect territories and other resources from competitors. Both male and female fruit flies of the species Drosophila melanogaster exhibit aggression in same-sex pairings, but the strategies used are sexually dimorphic. We have begun to explore the biological basis for the differing aggression strategies, and the cues promoting one form of aggression over the other. Here, we describe a line of genetically masculinized females that switch between male and female aggression patterns based on the sexual identity of their opponents. When these masculinized females are paired with more aggressive opponents, they increase the amount of male-like aggression they use, but do not alter the level of female aggression. This suggests that male aggression may be more highly responsive to behavioral cues than female aggression. Although the masculinized females of this line show opponent-dependent changes in aggression and courtship behavior, locomotor activity and sleep are unaffected. Thus, the driver line used may specifically masculinize neurons involved in social behavior. A discussion of possible different roles of male and female aggression in fruit flies is included here. These results can serve as precursors to future experiments aimed at elucidating the circuitry and triggering cues underlying sexually dimorphic aggressive behavior.

Octopamine neuromodulation regulates Gr32a-linked aggression and courtship pathways in Drosophila males.

Chemosensory pheromonal information regulates aggression and reproduction in many species, but how pheromonal signals are transduced to reliably produce behavior is not well understood. Here we demonstrate that the pheromonal signals detected by Gr32a-expressing chemosensory neurons to enhance male aggression are filtered through octopamine (OA, invertebrate equivalent of norepinephrine) neurons. Using behavioral assays, we find males lacking both octopamine and Gr32a gustatory receptors exhibit parallel delays in the onset of aggression and reductions in aggression. Physiological and anatomical experiments identify Gr32a to octopamine neuron synaptic and functional connections in the suboesophageal ganglion. Refining the Gr32a-expressing population indicates that mouth Gr32a neurons promote male aggression and form synaptic contacts with OA neurons. By restricting the monoamine neuron target population, we show that three previously identified OA-Fru(M) neurons involved in behavioral choice are among the Gr32a-OA connections. Our findings demonstrate that octopaminergic neuromodulatory neurons function as early as a second-order step in this chemosensory-driven male social behavior pathway.

Aggression and courtship in Drosophila: pheromonal communication and sex recognition.

Upon encountering a conspecific in the wild, males have to rapidly detect, integrate and process the most relevant signals to evoke an appropriate behavioral response. Courtship and aggression are the most important social behaviors in nature for procreation and survival: for males, making the right choice between the two depends on the ability to identify the sex of the other individual. In flies as in most species, males court females and attack other males. Although many sensory modalities are involved in sex recognition, chemosensory communication mediated by specific molecules that serve as pheromones plays a key role in helping males distinguish between courtship and aggression targets. The chemosensory signals used by flies include volatile and non-volatile compounds, detected by the olfactory and gustatory systems. Recently, several putative olfactory and gustatory receptors have been identified that play key roles in sex recognition, allowing investigators to begin to map the neuronal circuits that convey this sensory information to higher processing centers in the brain. Here, we describe how Drosophila melanogaster males use taste and smell to make correct behavioral choices.

Drosophila mutants lacking the glial neurotransmitter-modifying enzyme Ebony exhibit low neurotransmitter levels and altered behavior.

Inhibitors of enzymes that inactivate amine neurotransmitters (dopamine, serotonin), such as catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO), are thought to increase neurotransmitter levels and are widely used to treat Parkinson's disease and psychiatric disorders, yet the role of these enzymes in regulating behavior remains unclear. Here, we investigated the genetic loss of a similar enzyme in the model organism Drosophila melanogaster. Because the enzyme Ebony modifies and inactivates amine neurotransmitters, its loss is assumed to increase neurotransmitter levels, increasing behaviors such as aggression and courtship and decreasing sleep. Indeed, ebony mutants have been described since 1960 as "aggressive mutants," though this behavior has not been quantified. Using automated machine learning-based analyses, we quantitatively confirmed that ebony mutants exhibited increased aggressive behaviors such as boxing but also decreased courtship behaviors and increased sleep. Through tissue-specific knockdown, we found that ebony's role in these behaviors was specific to glia. Unexpectedly, direct measurement of amine neurotransmitters in ebony brains revealed that their levels were not increased but reduced. Thus, increased aggression is the anomalous behavior for this neurotransmitter profile. We further found that ebony mutants exhibited increased aggression only when fighting each other, not when fighting wild-type controls. Moreover, fights between ebony mutants were less likely to end with a clear winner than fights between controls or fights between ebony mutants and controls. In ebony vs. control fights, ebony mutants were more likely to win. Together, these results suggest that ebony mutants exhibit prolonged aggressive behavior only in a specific context, with an equally dominant opponent.

Sexually dimorphic peripheral sensory neurons regulate copulation duration and persistence in male Drosophila.

Peripheral sensory neurons are the gateway to the environment across species. In Drosophila, olfactory and gustatory senses are required to initiate courtship, as well as for the escalation of courtship patterns that lead to copulation. To be successful, copulation must last long enough to ensure the transfer of sperm and seminal fluid that ultimately leads to fertilization. The peripheral sensory information required to regulate copulation duration is unclear. Here, we employed genetic manipulations that allow driving gene expression in the male genitalia as a tool to uncover the role of these genitalia specific neurons in copulation. The fly genitalia contain sex-specific bristle hairs innervated by mechanosensory neurons. To date, the role of the sensory information collected by these peripheral neurons in male copulatory behavior is unknown. We confirmed that these MSNs are cholinergic and co-express both fru and dsx. We found that the sensory information received by the peripheral sensory neurons from the front legs (GRNs) and mechanosensory neurons (MSNs) at the male genitalia contribute to the regulation of copulation duration. Moreover, our results show that their function is required for copulation persistence, which ensures copulation is undisrupted in the presence of environmental stress before sperm transfer is complete.

Circadian remodeling of neuronal circuits involved in rhythmic behavior.

Clock output pathways are central to convey timing information from the circadian clock to a diversity of physiological systems, ranging from cell-autonomous processes to behavior. While the molecular mechanisms that generate and sustain rhythmicity at the cellular level are well understood, it is unclear how this information is further structured to control specific behavioral outputs. Rhythmic release of pigment dispersing factor (PDF) has been proposed to propagate the time of day information from core pacemaker cells to downstream targets underlying rhythmic locomotor activity. Indeed, such circadian changes in PDF intensity represent the only known mechanism through which the PDF circuit could communicate with its output. Here we describe a novel circadian phenomenon involving extensive remodeling in the axonal terminals of the PDF circuit, which display higher complexity during the day and significantly lower complexity at nighttime, both under daily cycles and constant conditions. In support to its circadian nature, cycling is lost in bona fide clockless mutants. We propose this clock-controlled structural plasticity as a candidate mechanism contributing to the transmission of the information downstream of pacemaker cells.

[Palmar-plantar erythrodysaesthesia syndrome local cold prevention]. / Eritrodisestesia palmoplantar: prevención con frío local.

OBJECTIVE: to evaluate the role of local cold applied to the tips on the prevention of palmar-plantar erythrodysaesthesia (PPE) caused by pegylated liposomal doxorubicin (PLD). MATERIALS AND METHODS: from may 2006 to june 2009, 8 patients with cutaneous T-cell lymphoma mycosis fungoides type were treated with PLD. The median age was 56 years and was administered a total of 63 cycle, with an average of 7.87 cycle per person, with a dose of PLD 20 mg/m2 every 2 weeks. All patients had premedication with dexamethasone, ondasetron and pyridoxine. At the time all were given prophylaxis with local cold for an hour RESULTS: only one patient had grade 4 PPE (12.5%), which appeared after the first cycle, subsequent can manage a total of 10. In absolute terms was recorded EPP grade 4 only 1.58% of cycles administered (1/63). In the remaining patients there was no degree of EPP. CONCLUSIONS: this paper demonstrates the effectiveness of several preventive measures (pyridoxine, corticosteroid and local cold) in the prevention of the PPE.

Sexual Dimorphism in Aggression: Sex-Specific Fighting Strategies Across Species.

Aggressive behavior is thought to have evolved as a strategy for gaining access to resources such as territory, food, and potential mates. Across species, secondary sexual characteristics such as competitive aggression and territoriality are considered male-specific behaviors. However, although female-female aggression is often a behavior that is displayed almost exclusively to protect the offspring, multiple examples of female-female competitive aggression have been reported in both invertebrate and vertebrate species. Moreover, cases of intersexual aggression have been observed in a variety of species. Genetically tractable model systems such as mice, zebrafish, and fruit flies have proven extremely valuable for studying the underlying neuronal circuitry and the genetic architecture of aggressive behavior under laboratory conditions. However, most studies lack ethological or ecological perspectives and the behavioral patterns available are limited. The goal of this review is to discuss each of these forms of aggression, male intrasexual aggression, intersexual aggression and female intrasexual aggression in the context of the most common genetic animal models and discuss examples of these behaviors in other species.

Open-source computational framework for studying Drosophila behavioral phase.

This protocol describes a standardized method for analyzing Drosophila behavioral rhythmicity under light dark cycles, temperature ramps, and free running conditions. The protocol constitutes a step-by-step guide from generation of appropriate Drosophila genetic crosses to behavioral experiments. We also provide an open-source computational framework using R for the analysis of the phase of behavior using circular statistics. An extended method for complete use is also provided. For complete details on the use and execution of this protocol, please refer to Fernandez et al. (2020).

Long-Term Dietary Restriction Leads to Development of Alternative Fighting Strategies.

In competition for food, mates and territory, most animal species display aggressive behavior through visual threats and/or physical attacks. Such naturally-complex social behaviors have been shaped by evolution. Environmental pressure, such as the one imposed by dietary regimes, forces animals to adapt to specific conditions and ultimately to develop alternative behavioral strategies. The quality of the food resource during contests influence animals' aggression levels. However, little is known regarding the effects of a long-term dietary restriction-based environmental pressure on the development of alternative fighting strategies. To address this, we employed two lines of the wild-type Drosophila melanogaster Canton-S (CS) which originated from the same population but raised under two distinct diets for years. One diet contained both proteins and sugar, while the second one was sugar-free. We set up male-male aggression assays using both CS lines and found differences in aggression levels and the fighting strategies employed to establish dominance relationships. CS males raised on a sugar-containing diet started fights with a physical attack and employed a high number of lunges for establishing dominance but displayed few wing threats throughout the fight. In contrast, the sugar-free-raised males favored wing threats as an initial aggressive demonstration and used fewer lunges to establish dominance, but displayed a higher number of wing threats. This study demonstrates that fruit flies that have been raised under different dietary conditions have adapted their patterns of aggressive behavior and developed distinct fighting strategies: one favoring physical attacks, while the other one favoring visual threats.

The axon-guidance roundabout gene alters the pace of the Drosophila circadian clock.

Great efforts have been directed to the dissection of the cell-autonomous circadian oscillator in Drosophila. However, less information is available regarding how this oscillator controls rhythmic rest-activity cycles. We have identified a viable allele of roundabout, robo(hy), where the period of locomotor activity is shortened. From its role in axon-pathfinding, we anticipated developmental defects in clock-relevant structures. However, robo(hy) produced minor defects in the architecture of the circuits essential for rhythmic behaviour. ROBO's presence within the circadian circuit strengthened the possibility of a novel role for ROBO at this postdevelopmental stage. Genetic interactions between pdf (01) and robo(hy) suggest that ROBO could alter the communication within different clusters of the circadian network, thus impinging on two basic properties, periodicity and/or rhythmicity. Early translocation of PERIOD to the nucleus in robo(hy) pacemaker cells indicated that shortened activity rhythms were derived from alterations in the molecular oscillator. Herein we present a mutation affecting clock function associated with a molecule involved in circuit assembly and maintenance.

Characterization of the Sexually Dimorphic fruitless Neurons That Regulate Copulation Duration.

Male courtship in Drosophila melanogaster is a sexually dimorphic innate behavior that is hardwired in the nervous system. Understanding the neural mechanism of courtship behavior requires the anatomical and functional characterization of all the neurons involved. Courtship involves a series of distinctive behavioral patterns, culminating in the final copulation step, where sperms from the male are transferred to the female. The duration of this process is tightly controlled by multiple genes. The fruitless (fru) gene is one of the factors that regulate the duration of copulation. Using several intersectional genetic combinations to restrict the labeling of GAL4 lines, we found that a subset of a serotonergic cluster of fru neurons co-express the dopamine-synthesizing enzyme, tyrosine hydroxylase, and provide behavioral and immunological evidence that these neurons are involved in the regulation of copulation duration.

Análisis de los componentes en la adquisición de la lectura en castellano: una aplicación del modelo logístico lineal / Component analysis of Spanish reading process: an application of the linear logistic test model

Se analizan los componentes básicos para la adquisición de la lectura en castellano mediante la aplicación del modelo logístico lineal de Fisher (Linear Logistic Test Model [LLTM]). Participaron en el estudio 245 niños y niñas de edades comprendidas entre los 4 y los 9 años a los que se administró una extensa batería diseñada para evaluar distintos procesos básicos para la lectura (PROBALES). Se aplicaron técnicas de análisis factorial para seleccionar un subconjunto de ítems que mostrasen ajuste al modelo de Rasch. El LLTM permitió confirmar la validez del modelo teórico según el cual el aprendizaje de la lectura descansa en el desarrollo de tres habilidades básicas: reconocimiento de palabras, conciencia fonológica y comprensión de la lectura. Se muestra la capacidad predictiva del modelo mediante análisis discriminante, y se constata que se clasificó correctamente en su curso escolar al 68% de los participantes.

The basic components for the acquisition of reading in Spanish are analyzed by using the Fisher Linear Logistic Test Model (LLTM). An extensive battery designed to assess different Basic Processes for Reading (PROBALES, acronym in Spanish) was applied to 245 children aged 4 to 9. Factor analysis techniques were used to select a subset of items that would adjust to the Rasch model. The LLTM confirmed the validity of the theoretical model which states that reading acquisition relies on the development of three basic skills: word recognition, phonological awareness, and reading comprehension. The theoretical model's predictive ability is shown by discriminant analysis, thereby confirming that 68% of participants were correctly classified in their school grade.

A functional misexpression screen uncovers a role for enabled in progressive neurodegeneration.

Drosophila is a well-established model to study the molecular basis of neurodegenerative diseases. We carried out a misexpression screen to identify genes involved in neurodegeneration examining locomotor behavior in young and aged flies. We hypothesized that a progressive loss of rhythmic activity could reveal novel genes involved in neurodegenerative mechanisms. One of the interesting candidates showing progressive arrhythmicity has reduced enabled (ena) levels. ena down-regulation gave rise to progressive vacuolization in specific regions of the adult brain. Abnormal staining of pre-synaptic markers such as cystein string protein (CSP) suggest that axonal transport could underlie the neurodegeneration observed in the mutant. Reduced ena levels correlated with increased apoptosis, which could be rescued in the presence of p35, a general Caspase inhibitor. Thus, this mutant recapitulates two important features of human neurodegenerative diseases, i.e., vulnerability of certain neuronal populations and progressive degeneration, offering a unique scenario in which to unravel the specific mechanisms in an easily tractable organism.

Eritrodisestesia palmoplantar. Prevención con frío local / Palmar-plantar erythrodysaesthesia syndrome local cold prevention

Objetivos: evaluar la labor del frío local aplicado sobre las extremidades en la prevención de la eritrodisestesia palmoplantar (EPP) ocasionada por la doxorrubicina liposomal pegilada (DLP). Material y Métodos: en el periodo comprendido entre mayo de 2006 y junio de 2009 se trató un total de ocho pacientes con linfoma cutáneo de células T tipo micosis fungoide en estadios avanzados. La media de edad fue de 56 años, administrándose un total de 63 ciclos, con una media de 7,87 ciclos/persona, con una dosis de DLP de 20mg/m2 cada dos semanas. A todos los pacientes se les premedicó con dexametasona, ondasetron y piridoxina. A su vez se les administró profilaxis con frío local durante una hora. Resultados: de los ocho pacientes tratados, únicamente se objetivó una EPP grado 4 en uno de ellos (12,5%), que apareció tras el primer ciclo, pudiendo administrar los ciclos posteriores hasta un total de 10. En términos absolutos se registró EPP grado 4 únicamente en un 1,58% de los ciclos administrados (1/63). En el resto de los pacientes no se registró ninguno. Conclusiones: se demuestra la eficacia de las diferentes medidas de prevención (piridoxina, corticoides y frío local) en la prevención de PersonNameProductIDla EPP.la EPP(AU)

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