Mmp1 processing of the PDF neuropeptide regulates circadian structural plasticity of pacemaker neurons.

In the Drosophila brain, the neuropeptide PIGMENT DISPERSING FACTOR (PDF) is expressed in the small and large Lateral ventral neurons (LNvs) and regulates circadian locomotor behavior. Interestingly, PDF immunoreactivity at the dorsal terminals changes across the day as synaptic contacts do as a result of a remarkable remodeling of sLNv projections. Despite the relevance of this phenomenon to circuit plasticity and behavior, the underlying mechanisms remain poorly understood. In this work we provide evidence that PDF along with matrix metalloproteinases (Mmp1 and 2) are key in the control of circadian structural remodeling. Adult-specific downregulation of PDF levels per se hampers circadian axonal remodeling, as it does altering Mmp1 or Mmp2 levels within PDF neurons post-developmentally. However, only Mmp1 affects PDF immunoreactivity at the dorsal terminals and exerts a clear effect on overt behavior. In vitro analysis demonstrated that PDF is hydrolyzed by Mmp1, thereby suggesting that Mmp1 could directly terminate its biological activity. These data demonstrate that Mmp1 modulates PDF processing, which leads to daily structural remodeling and circadian behavior.

Circadian period integrates network information through activation of the BMP signaling pathway.

Living organisms use biological clocks to maintain their internal temporal order and anticipate daily environmental changes. In Drosophila, circadian regulation of locomotor behavior is controlled by ∼150 neurons; among them, neurons expressing the PIGMENT DISPERSING FACTOR (PDF) set the period of locomotor behavior under free-running conditions. To date, it remains unclear how individual circadian clusters integrate their activity to assemble a distinctive behavioral output. Here we show that the BONE MORPHOGENETIC PROTEIN (BMP) signaling pathway plays a crucial role in setting the circadian period in PDF neurons in the adult brain. Acute deregulation of BMP signaling causes period lengthening through regulation of dClock transcription, providing evidence for a novel function of this pathway in the adult brain. We propose that coherence in the circadian network arises from integration in PDF neurons of both the pace of the cell-autonomous molecular clock and information derived from circadian-relevant neurons through release of BMP ligands.

Retrograde bone morphogenetic protein signaling shapes a key circadian pacemaker circuit.

The neuropeptide pigment-dispersing factor (PDF) synchronizes molecular oscillations within circadian pacemakers in the Drosophila brain. It is expressed in the small ventral lateral neurons (sLNvs) and large ventral lateral neurons, the former being indispensable for maintaining behavioral rhythmicity under free-running conditions. How PDF circuits develop the specific connectivity traits that endow such global behavioral control remains unknown. Here, we show that mature sLNv circuits require PDF signaling during early development, acting through its cognate receptor PDFR at postsynaptic targets. Yet, axonal defects by PDF knockdown are presynaptic and become apparent only after metamorphosis, highlighting a delayed response to a signal released early on. Presynaptic expression of constitutively active bone morphogenetic protein (BMP) receptors prevents pdfr mutants misrouting phenotype, while sLNv-restricted downregulation of BMP signaling components phenocopied pdf(01). Thus, we have uncovered a novel mechanism that provides an early "tagging" of synaptic targets that will guide circuit refinement later in development.

Neurons with names: Descending control and sensorimotor processing in insect motor control.

Technical and methodological advances in recent years have brought new ways to tackle major classical questions in insect motor control. Particularly, significant advancements were achieved in comprehending brain descending control by characterizing descending neurons, their targets in the ventral nerve cord (VNC), and how local networks there integrate sensory information. While physiological experiments in larger insects brought us a better understanding of how sensory modalities are processed locally in the VNC, the development and improvement of genetic tools, principally in Drosophila, opened the door to individually characterize actors at these three levels of information flow in behavioral control. This brief review brings together the names and roles of some of those actors, by highlighting the most significant findings from our perspective.

Collective action or individual choice: Spontaneity and individuality contribute to decision-making in Drosophila.

Our own unique character traits make our behavior consistent and define our individuality. Yet, this consistency does not entail that we behave repetitively like machines. Like humans, animals also combine personality traits with spontaneity to produce adaptive behavior: consistent, but not fully predictable. Here, we study an iconically rigid behavioral trait, insect phototaxis, that nevertheless also contains both components of individuality and spontaneity. In a light/dark T-maze, approximately 70% of a group of Drosophila fruit flies choose the bright arm of the T-Maze, while the remaining 30% walk into the dark. Taking the photopositive and the photonegative subgroups and re-testing them reveals the spontaneous component: a similar 70-30 distribution emerges in each of the two subgroups. Increasing the number of choices to ten choices, reveals the individuality component: flies with an extremely negative series of first choices were more likely to show photonegative behavior in subsequent choices and vice versa. General behavioral traits, independent of light/dark preference, contributed to the development of this individuality. The interaction of individuality and spontaneity together explains why group averages, even for such seemingly stereotypical behaviors, are poor predictors of individual choices.

Prevalence of obesity in 4-18-year-old population in the Basque Country, Spain.

The objective of the study was to estimate the prevalence of overweight and obesity in children and adolescents in the Basque Country, Spain. It consisted of an analysis of baseline data of the Nutrition Survey, a cross-sectional study, carried out in 2004-2005. The study population comprised child and adolescent living in the Basque Country. The analysis was carried out in a representative random sample of 1178 people aged 4-18 years. Anthropometric examinations were undertaken by trained observers using standardized methods and included measurements of weight and height. Subjects were classified into different body mass index categories, according to the International Obesity Task Force guidelines. A 5.4% of the population studied was obese; 6% of males and 4.7% of females, the highest in the 11-14 age group in boys (7.2%) and in the 4-6 age group in girls (12.5%). Overweight (22.9%) was slightly higher in girls. The highest prevalence of excess weight (overweight+obesity) was observed in girls aged 4-6 years (38.4%), decreasing with age. Subjects in the 15-18 age group rated 16.6%. Boys evidenced a higher excess weight rate in the 11-14 (32.9%) and 7-10 (32%) age groups; the lowest rate was found in the 4-6 age group. Prevalence of obesity was higher in the less privileged socio-economic strata (6.9% vs. 5.2%), for both boys and girls. However, this trend was observed only in girls for overweight (25.9% vs. 21.8%). This study shows a high prevalence of obesity and overweight in the studied population and similar to other European countries and regions.

A decision underlies phototaxis in an insect.

Like a moth into the flame-phototaxis is an iconic example for innate preferences. Such preferences probably reflect evolutionary adaptations to predictable situations and have traditionally been conceptualized as hard-wired stimulus-response links. Perhaps for that reason, the century-old discovery of flexibility in Drosophila phototaxis has received little attention. Here, we report that across several different behavioural tests, light/dark preference tested in walking is dependent on various aspects of flight. If we temporarily compromise flying ability, walking photopreference reverses concomitantly. Neuronal activity in circuits expressing dopamine and octopamine, respectively, plays a differential role in photopreference, suggesting a potential involvement of these biogenic amines in this case of behavioural flexibility. We conclude that flies monitor their ability to fly, and that flying ability exerts a fundamental effect on action selection in Drosophila This work suggests that even behaviours which appear simple and hard-wired comprise a value-driven decision-making stage, negotiating the external situation with the animal's internal state, before an action is selected.

Influence of starvation on sucrase regulation by dietary sucrose in the rat.

We have studied the action of sucrose on jejunal sucrase activity. Rats (175 g) were first starved or fed a digestible carbohydrate-free diet for 60 h and then fed a high sucrose diet for varying times up to 84 h. 1) Rats starved for 60 h showed mucosal atrophy with a decrease in protein content/10 cm (18.00 +/- 1.4 versus 40.1 +/- 3 mg (controls p less than 0.001) and in villus height (357 +/- 18 versus 526 +/- 5 microns, p less than 0.001) which was fully repaired only after 60 h on the sucrose diet (528 +/- 11 microns). Rats on digestible carbohydrate-free diet showed no mucosal atrophy. 2) Starved rats had a delayed (60 h) sucrase activity response to sucrose (53 +/- 7 versus 122 +/- 4 microns/mg protein, p less than 0.001). Maximum activity was obtained after 12 h on sucrose diet in rats maintained on the carbohydrate-free diet: 38 +/- 1 versus 108 +/- 2.3 microns/mg protein, p less than 0.001. 3) Villus and crypt cell analysis after starvation and 12 h on a high sucrose diet localized the increase in sucrase activity to the villus-crypt junction. No change occurred in the upper villus. The increase was complete all along the villus by 36 h. In contrast, after the carbohydrate-free diet, sucrase activity increased maximally at all levels of the villus by 12 h on the high sucrose diet.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of fasting and refeeding on the adaptation of the small intestine in rats. A model for physiopathologic studies]. / Effet du jeûne et de la réalimentation sur l'adaptation de l'intestin grêle chez le rat. Un modèle d'études physio-pathologiques.

A chronological study was carried out on 50 male Wistar rats (350 g) to determine the effects of 3 days of fasting and 16 h to 9 days of refeeding on the morphology of jejunal and ileal mucosa (villus, crypt and enterocyte heights; number of mitosis), on some aspects of their functional adaptation (sucrase, maltase, protein) and on nitrogen and lipid absorptions. Three days of fasting resulted in weight loss (12 p. 100), in a jejunal mucosa atrophy (villus height: 376 +/- 18 vs. 492 +/- 4 microns in controls; enterocyte height: 31 +/- 2 vs. 41 +/- 0.3 micron in controls) and a decrease in disaccharidases activities (sucrase: 927 +/- 90 vs. 3,363 +/- 21 mU/10 cm length in controls). No change in ileal mucosa morphometry was noticed. Ad libitum refeeding caused a rapid and progressive weight gain, a jejunal morphometric regrowth identical to control values at 16 h (villus height: 521 +/- 20, enterocyte height 42 +/- 0.9 microns), and maximum at 40 h of refeeding (villus height: 601 +/- 5 microns). Disaccharidases adaptation was delayed, with a maximum at 64 h of refeeding (sucrase: 3,524 +/- 56 mU/10 cm length). Despite a 30 p. 100 increase of food consumption over the whole study (45 p. 100 during the first 16 h of refeeding), nitrogen and lipid absorption coefficients remained identical to those found in controls with an increased nitrogen balance of 70 p. 100 at 16 h and 54 p. 100 at 40 h refeeding, as compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

[Prevalence of hepatitis B infection in institutions for the mentally retarded. Epidemiologic characteristics in the province of Vizcaya]. / Prevalencia de infección por el virus de la hepatitis B en instituciones de deficientes mentales. Características epidemiológicas en la provincia de Vizcaya.

The prevalence of hepatitis B virus (HBV) infection was studied in 346 subjects (148 employees and 198 mentally retarded) in four institutions for the mentally subnormal in Vizcaya-Spain. The prevalence of markers in the overall group was 32.6%; 13.5% in the employees and 46.9% in the mentally retarded. Early age and institutionalization time increases the risk of infection in the mentally retarded group, but not in the employees group. 220 subjects (118 employees and 102 mentally retarded) had negative HBV markers and were vaccinated with recombinant-DNA hepatitis B vaccine. The immunogenicity was 80% and the weight-height index the only factor implicit in the group of subjects no seroconverters. The reactogenicity of vaccine was 6.7%.

Circadian pacemaker neurons change synaptic contacts across the day.

Daily cycles of rest and activity are a common example of circadian control of physiology. In Drosophila, rhythmic locomotor cycles rely on the activity of 150-200 neurons grouped in seven clusters [1, 2]. Work from many laboratories points to the small ventral lateral neurons (sLNvs) as essential for circadian control of locomotor rhythmicity [3-7]. sLNv neurons undergo circadian remodeling of their axonal projections, opening the possibility for a circadian control of connectivity of these relevant circadian pacemakers [8]. Here we show that circadian plasticity of the sLNv axonal projections has further implications than mere structural changes. First, we found that the degree of daily structural plasticity exceeds that originally described [8], underscoring that changes in the degree of fasciculation as well as extension or pruning of axonal terminals could be involved. Interestingly, the quantity of active zones changes along the day, lending support to the attractive hypothesis that new synapses are formed while others are dismantled between late night and the following morning. More remarkably, taking full advantage of the GFP reconstitution across synaptic partners (GRASP) technique [9], we showed that, in addition to new synapses being added or removed, sLNv neurons contact different synaptic partners at different times along the day. These results lead us to propose that the circadian network, and in particular the sLNv neurons, orchestrates some of the physiological and behavioral differences between day and night by changing the path through which information travels.

[The costs of operating psychiatric hospitals of the Ministry of Health in the Federal District]. / Costos de operación de hospitales psiquiátricos de la Secretaría de Salud en el Distrito Federal.

The hospitals of the Ministry of Health in Mexico City, particularly psychiatric hospitals, have been confronting operational problems due to a scarce budget and lack of informational on their operation and costs. The present study intends to begin to solve some of those problems through an initial diagnosis. A form was designed for data harvesting, which enables to sort costs by class (direct and indirect). This information was projected in a worksheet and analyzed by service, day-bed and unity as a whole. The results show an inequitable distribution of the budget among hospitals.