The P450 oxidoreductase, RedA, controls development beyond the mound stage in Dictyostelium discoideum

Background: NADPH-cytochrome- P450 oxidoreductase (CPR) is a ubiquitous enzyme that belongs to a family of diflavin oxidoreductases and is required for activity of the microsomal cytochrome-P450 monooxygenase system. CPR gene-disruption experiments have demonstrated that absence of this enzyme causes developmental defects both in mouse and insect. Results: Annotation of the sequenced genome of D. discoideum revealed the presence of three genes (redA, redB and redC) that encode putative members of the diflavin oxidoreductase protein family. redA transcripts are present during growth and early development but then decline, reaching undetectable levels after the mound stage. redB transcripts are present in the same levels during growth and development while redC expression was detected only in vegetative growing cells. We isolated a mutant strain of Dictyostelium discoideum following restriction enzyme-mediated integration (REMI) mutagenesis in which redA was disrupted. This mutant develops only to the mound stage and accumulates a bright yellow pigment. The mound-arrest phenotype is cell-autonomous suggesting that the defect occurs within the cells rather than in intercellular signaling. Conclusion: The developmental arrest due to disruption of redA implicates CPR in the metabolism of compounds that control cell differentiation.

Physical controls on carbon dioxide transfer velocity and flux in low-gradient river systems and implications for regional carbon budgets

Outgassing of carbon dioxide (CO(2)) from rivers and streams to the atmosphere is a major loss term in the coupled terrestrial-aquatic carbon cycle of major low-gradient river systems (the term ""river system"" encompasses the rivers and streams of all sizes that compose the drainage network in a river basin). However, the magnitude and controls on this important carbon flux are not well quantified. We measured carbon dioxide flux rates (F(CO2)), gas transfer velocity (k), and partial pressures (p(CO2)) in rivers and streams of the Amazon and Mekong river systems in South America and Southeast Asia, respectively. F(CO2) and k values were significantly higher in small rivers and streams (channels <100 m wide) than in large rivers (channels >100 m wide). Small rivers and streams also had substantially higher variability in k values than large rivers. Observed F(CO2) and k values suggest that previous estimates of basinwide CO(2) evasion from tropical rivers and wetlands have been conservative and are likely to be revised upward substantially in the future. Data from the present study combined with data compiled from the literature collectively suggest that the physical control of gas exchange velocities and fluxes in low-gradient river systems makes a transition from the dominance of wind control at the largest spatial scales (in estuaries and river mainstems) toward increasing importance of water current velocity and depth at progressively smaller channel dimensions upstream. These results highlight the importance of incorporating scale-appropriate k values into basinwide models of whole ecosystem carbon balance.

Gaseous and fluvial carbon export from an Amazon forest watershed

The transfer of carbon (C) from Amazon forests to aquatic ecosystems as CO(2) supersaturated in groundwater that outgases to the atmosphere after it reaches small streams has been postulated to be an important component of terrestrial ecosystem C budgets. We measured C losses as soil respiration and methane (CH(4)) flux, direct CO(2) and CH(4) fluxes from the stream surface and fluvial export of dissolved inorganic C (DIC), dissolved organic C (DOC), and particulate C over an annual hydrologic cycle from a 1,319-ha forested Amazon perennial first-order headwater watershed at Tanguro Ranch in the southern Amazon state of Mato Grosso. Stream pCO(2) concentrations ranged from 6,491 to 14,976 mu atm and directly-measured stream CO(2) outgassing flux was 5,994 +/- A 677 g C m(-2) y(-1) of stream surface. Stream pCH(4) concentrations ranged from 291 to 438 mu atm and measured stream CH(4) outgassing flux was 987 +/- A 221 g C m(-2) y(-1). Despite high flux rates from the stream surface, the small area of stream itself (970 m(2), or 0.007% of watershed area) led to small directly-measured annual fluxes of CO(2) (0.44 +/- A 0.05 g C m(2) y(-1)) and CH(4) (0.07 +/- A 0.02 g C m(2) y(-1)) per unit watershed land area. Measured fluvial export of DIC (0.78 +/- A 0.04 g C m(-2) y(-1)), DOC (0.16 +/- A 0.03 g C m(-2) y(-1)) and coarse plus fine particulate C (0.001 +/- A 0.001 g C m(-2) y(-1)) per unit watershed land area were also small. However, stream discharge accounted for only 12% of the modeled annual watershed water output because deep groundwater flows dominated total runoff from the watershed. When C in this bypassing groundwater was included, total watershed export was 10.83 g C m(-2) y(-1) as CO(2) outgassing, 11.29 g C m(-2) y(-1) as fluvial DIC and 0.64 g C m(-2) y(-1) as fluvial DOC. Outgassing fluxes were somewhat lower than the 40-50 g C m(-2) y(-1) reported from other Amazon watersheds and may result in part from lower annual rainfall at Tanguro. Total stream-associated gaseous C losses were two orders of magnitude less than soil respiration (696 +/- A 147 g C m(-2) y(-1)), but total losses of C transported by water comprised up to about 20% of the +/- A 150 g C m(-2) (+/- 1.5 Mg C ha(-1)) that is exchanged annually across Amazon tropical forest canopies.

Propofol-induced sleep: Polysomnographic evaluation of patients with obstructive sleep apnea and controls

OBJECTIVE: The localization of upper airway obstruction in patients with obstructive sleep apnea (OSA) may optimize treatment. Nasoendoscopy during propofol sedation allows such an evaluation, but the effect of this drug on respiratory patterns and muscle relaxation is unknown. The objective of the present study was to determine through polysomnography whether propofol would change sleep parameters. STUDY DESIGN: Prospective study of subjects submitted to polysomnography under sedation with propofol. SETTING: Tertiary referral center. SUBJECTS AND METHODS: Fifteen non-obese subjects (4 controls/11 OSA patients) were submitted to two diurnal polysomnograms (90-120 minutes of sleep), with and without the use of propofol. The parameters presence of snoring, apnea-hypopnea index (AHI), oxygen desaturation, and sleep architecture were compared. RESULTS: The use of propofol did not induce snoring in the control subjects, whereas 100 percent of the OSA patients snored. AHI and mean oxygen saturation (SaO(2)) did not differ significantly between examinations with and without sedation. However, minimum SaO(2) differed significantly (P < 0.05) with sedation, being lower during propofol sedation. Propofol also significantly changed the sleep architecture, with a significant increase in N3 sleep (P < 0.005) and total abolishment of rapid eye movement sleep (P < 0.0005) during propofol sedation. CONCLUSIONS: These preliminary results allow us to infer that sedation with propofol changes sleep architecture but permits respiratory evaluation, because the main respiratory parameters evaluated in OSA are maintained. These preliminary results support the view that nasoendoscopy under propofol sedation is a promising examination for management of this disease. (C) 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved.

A Fault-Tolerant Manipulator Robot Based on H(2), H(infinity), and Mixed H(2)/H(infinity) Markovian Controls

This paper develops a Markovian jump model to describe the fault occurrence in a manipulator robot of three joints. This model includes the changes of operation points and the probability that a fault occurs in an actuator. After a fault, the robot works as a manipulator with free joints. Based on the developed model, a comparative study among three Markovian controllers, H(2), H(infinity), and mixed H(2)/H(infinity) is presented, applied in an actual manipulator robot subject to one and two consecutive faults.

Application of thermal sums concept to estimate the time to harvest new banana hybrids for export

Application of the thermal sum concept was developed to determine the optimal harvesting stage of new banana hybrids to be grown for export. It was tested on two triploid hybrid bananas, FlhorBan 916 (F916) and FlhorBan 918 (F918), created by CIRAD`s banana breeding programme, using two different approaches. The first approach was used with F916 and involved calculating the base temperature of bunches sampled at two sites at the ripening stage, and then determining the thermal sum at which the stage of maturity would be identical to that of the control Cavendish export banana. The second approach was used to assess the harvest stage of F918 and involved calculating the two thermal parameters directly, but using more plants and a longer period. Using the linear regression model, the estimated thermal parameters were a thermal sum of 680 degree-days (dd) at a base temperature of 17.0 degrees C for cv. F916, and 970 dd at 13.9 degrees C for cv. F918. This easy-to-use method provides quick and reliable calculations of the two thermal parameters required at a specific harvesting stage for a given banana variety in tropical climate conditions. Determining these two values is an essential step for gaining insight into the agronomic features of a new variety and its potential for export. (C) 2011 Elsevier B.V. All rights reserved.

Cdc42p controls yeast-cell shape and virulence of Paracoccidioides brasiliensis

Paracoccidioides brasiliensis is characterized by a multiple budding phenotype and a polymorphic cell growth, leading to the formation of cells with extreme variations in shape and size. Since Cdc42 is a pivotal molecule in establishing and maintaining polarized growth for diverse cell types, as well as during pathogenesis of certain fungi, we evaluated its role during cell growth and virulence of the yeast-form of P. brasiliensis. We used antisense technology to knock-down PbCDC42`s expression in P. brasiliensis yeast cells, promoting a decrease in cell size and more homogenous cell growth, altering the typical polymorphism of wild-type cells. Reduced expression levels also lead to increased phagocytosis and decreased virulence in a mouse model of infection. We provide genetic evidences underlying Pbcdc42p as an important protein during host-pathogen interaction and the relevance of the polymorphic nature and cell size in the pathogenesis of P. brasiliensis. (C) 2009 Elsevier Inc. All rights reserved.

Test–retest repeatability of self-reported environmental exposures in Parkinson’s disease cases and healthy controls

There is substantial disagreement among published epidemiological studies regarding environmental risk factors for Parkinson’s disease (PD). Differences in the quality of measurement of environmental exposures may contribute to this variation. The current study examined the test–retest repeatability of self-report data on risk factors for PD obtained from a series of 32 PD cases recruited from neurology clinics and 29 healthy sex-, age-and residential suburb-matched controls. Exposure data were collected in face-to-face interviews using a structured questionnaire derived from previous epidemiological studies. High repeatability was demonstrated for ‘lifestyle’ exposures, such as smoking and coffee/tea consumption (kappas 0.70–1.00). Environmental exposures that involved some action by the person, such as pesticide application and use of solvents and metals, also showed high repeatability (kappas>0.78). Lower repeatability was seen for rural residency and bore water consumption (kappa 0.39–0.74). In general, we found that case and control participants provided similar rates of incongruent and missing responses for categorical and continuous occupational, domestic, lifestyle and medical exposures.

The co-segregation of psychosis and selected physical disorders within families of patients with psychosis versus well controls

While it has been reported that individuals with psychosis are at increased or decreased risk of various physical disorders such as cancer and rheumatoid arthritis, there has been less research on the co-segregation of physical disorders within the first-degree relatives of those with psychosis compared to relatives of well controls. The aim of this study was to examine these issues in an epidemiologically informed catchment-area based case-control study. Patients with psychosis were drawn from a prevalence study undertaken as part of the Australian National Mental Health Survey. In addition, we recruited well controls who resided in the same catchment area. For each subject, we drew pedigrees and used a structured checklist to assess the presence of selected psychiatric disorders, and selected disorders such as multiple sclerosis, epilepsy, spina bifida, thyroid disorders, diabetes, asthma and eczema. Data based on pedigrees from 293 individuals with psychosis and 292 well controls was available. As expected, the odds of havingschizophrenia and affective disorders were significantly increased in the families of cases versus controls. The odds of havingeczema were significantly reduced in the relatives of those with psychosis. All other disorders occurred with equal frequency in cases versus control pedigrees. Current theories of eczema suggest that an absence of early life exposure to antigens and infectious agents may fail to prime the na¨ıve immune system, and leave the person at increased risk of eczema. The results of this study suggest that genetic andror environmental factors that facilitate psychosis may protect against eczema. The Stanley Foundation supported this project.

Myb-binding Protein 1a is a Nucleocytoplasmic Shuttling Protein that Utilizes CRM1-dependent and Independent Nuclear Export Pathways

Myb-binding protein 1a (Mybbp1a) is a novel nuclear protein localized predominantly, but not exclusively, in nucleoli. Although initially isolated as a c-Myb interacting protein, Mybbp1a is expressed ubiquitously, associates with a number of different transcription factors, and may play a role in both RNA polymerase I- and II-mediated transcriptional regulation. However, its precise function remains unclear. In this study we show that Mybbp1a is a nucleocytoplasmic shuttling protein and investigate the mechanisms responsible for both nuclear import and export. The carboxyl terminus of Mybbp1a, which contains seven short basic amino acid repeat sequences, is responsible for both nuclear and nucleolar localization, and this activity can be transferred to a heterologous protein. Deletion mapping demonstrated that these repeat sequences appear to act incrementally, with successive deletions resulting in a corresponding increase in the proportion of protein localized in the cytoplasm. Glutathione S-transferase pulldown experiments showed that the nuclear receptor importin-alpha/beta mediates Mybbp1a nuclear import. Interspecies heterokaryons were used to demonstrate that Mybbp1a was capable of shuttling between the nucleus and the cytoplasm. Deletion analysis and in vivo export studies using a heterologous assay system identified several nuclear export sequences which facilitate Mybbp1a nuclear export of Mybbp1a by CRM1-dependent and -independent pathways. (C) 2003 Elsevier Science (USA). All rights reserved.

Tenoxicam controls pain without altering orthodontic movement of maxillary canines

Arantes GM, Arantes VMN, Ashmawi HA, Posso IP To study the efficacy of tenoxicam for pain control, its potential for preemptive analgesia, and its influence on the orthodontic movement of upper canine teeth. This was a randomized controlled double-blind cross-over study. The patients were divided into three groups. Two groups received tenoxicam in daily doses of 20 mg orally for 3 days. Group A received the first dose of the drug before orthodontic activation and group B, just afterwards. Group C (control) received a placebo for 3 days. All groups had access to 750 mg of paracetamol up to four times a day. Three orthodontic activations were performed at 30-day intervals. Each patient belonged to two different groups. Pain intensity was assessed using a descriptive Pain Scale and a Visual Analog Scale. Private clinic; 36 patients undergoing bilateral canine tooth retraction. The statistical analysis did not show any difference in movement between the active groups and the control at any time. There was no statistical difference between the groups that received tenoxicam. Pain intensity in these groups was lower than in the placebo group. The difference in pain intensity between the active groups and the control was greatest at the assessment made 12 h after activation and it tended to zero, 72 h after activation. Tenoxicam did not influence orthodontic movement of the upper canines. It was effective for pain control and did not present any preemptive analgesic effect.

Performance on tests sensitive to impaired executive ability in schizophrenia, mania and well controls: acute and subacute phases

Aims: To compare the performance of schizophrenia, mania and well control groups on tests sensitive to impaired executive ability, and to assess the within-group stability of these measures across the acute and subacute phases of psychoses. Method: Recently admitted patients with schizophrenia (n=36), mania (n=18) and a well control group (n=20) were assessed on two occasions separated by 4 weeks. Tests included: the Controlled Oral Word Association Test, the Stroop Test, the Wisconsin Card Sort Test, and the Trail Making Test. Results: The two patient groups were significantly impaired on the Stroop Test at both time points compared to the control group. Significant group differences were also found for the Trail Making Test at Time 1 and for the Wisconsin Card Sort Test at Time 2. When controlled for practice effect, significant improvements over time were found on the Stroop and Trail Making tests in the schizophrenia group and on WCST Categories Achieved in the mania group. Discussion: Compared to controls, the patient groups were impaired on measures related to executive ability. The pattern of improvement on test scores between the acute and subacute phases differed between patients with schizophrenia versus patients with mania. (C) 1997 Elsevier Science B.V.

Challenges and Recommendations for Placebo Controls in Randomized Trials in Physical and Rehabilitation Medicine A Report of the International Placebo Symposium Working Group

Compared with other specialties, the field of physical and rehabilitation medicine has not received the deserved recognition from clinicians and researchers in the scientific community. One of the reasons is the lack of sound evidence to support the traditional physical and rehabilitation medicine treatments. The best way to change this disadvantage is through a well conducted clinical research, such as standard placebo- or sham-controlled randomized clinical trials. Therefore, having placebo groups in clinical trials is essential to improve the level of evidence-based practice in physical and rehabilitation medicine that ultimately translates to better clinical care. To address the challenges for the use of placebo in physical and rehabilitation medicine and randomized clinical trials and to create useful recommendations, we convened a working group during the inaugural International Symposium in Placebo (February 2009, in Sao Paulo, Brazil) in which the following topics were discussed: (1) current status of randomized clinical trials in physical and rehabilitation medicine, (2) challenges for the use of placebo in physical and rehabilitation medicine, (3) bioethics, (4) use of placebo in acupuncture trials and for the treatment of low-back pain, (5) mechanisms of placebo, and (6) insights from other specialties. The current article represents the consensus report from the working group.