The Crosslinking Degree Controls The Mechanical, Rheological, And Swelling Properties Of Hyaluronic Acid Microparticles.

Viscosupplements, used for treating joint and cartilage diseases, restore the rheological properties of synovial fluid, regulate joint homeostasis and act as scaffolds for cell growth and tissue regeneration. Most viscosupplements are hydrogels composed of hyaluronic acid (HA) microparticles suspended in fluid HA. These microparticles are crosslinked with chemicals to assure their stability against enzyme degradation and to prolong the action of the viscosupplement. However, the crosslinking also modifies the mechanical, swelling and rheological properties of the HA microparticle hydrogels, with consequences on the effectiveness of the application. The aim of this study is to correlate the crosslinking degree (CD) with these properties to achieve modulation of HA/DVS microparticles through CD control. Because divinyl sulfone (DVS) is the usual crosslinker of HA in viscosupplements, we examined the effects of CD by preparing HA microparticles at 1:1, 2:1, 3:1, and 5:1 HA/DVS mass ratios. The CD was calculated from inductively coupled plasma spectrometry data. HA microparticles were previously sized to a mean diameter of 87.5 µm. Higher CD increased the viscoelasticity and the extrusion force and reduced the swelling of the HA microparticle hydrogels, which also showed Newtonian pseudoplastic behavior and were classified as covalent weak. The hydrogels were not cytotoxic to fibroblasts according to an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2014.

Metabolic Memory Of ß-cells Controls Insulin Secretion And Is Mediated By Camkii.

Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) functions both in regulation of insulin secretion and neurotransmitter release through common downstream mediators. Therefore, we hypothesized that pancreatic ß-cells acquire and store the information contained in calcium pulses as a form of metabolic memory, just as neurons store cognitive information. To test this hypothesis, we developed a novel paradigm of pulsed exposure of ß-cells to intervals of high glucose, followed by a 24-h consolidation period to eliminate any acute metabolic effects. Strikingly, ß-cells exposed to this high-glucose pulse paradigm exhibited significantly stronger insulin secretion. This metabolic memory was entirely dependent on CaMKII. Metabolic memory was reflected on the protein level by increased expression of proteins involved in glucose sensing and Ca(2+)-dependent vesicle secretion, and by elevated levels of the key ß-cell transcription factor MAFA. In summary, like neurons, human and mouse ß-cells are able to acquire and retrieve information.

Hypothalamic S1p/s1pr1 Axis Controls Energy Homeostasis.

Sphingosine 1-phosphate receptor 1 (S1PR1) is a G-protein-coupled receptor for sphingosine-1-phosphate (S1P) that has a role in many physiological and pathophysiological processes. Here we show that the S1P/S1PR1 signalling pathway in hypothalamic neurons regulates energy homeostasis in rodents. We demonstrate that S1PR1 protein is highly enriched in hypothalamic POMC neurons of rats. Intracerebroventricular injections of the bioactive lipid, S1P, reduce food consumption and increase rat energy expenditure through persistent activation of STAT3 and the melanocortin system. Similarly, the selective disruption of hypothalamic S1PR1 increases food intake and reduces the respiratory exchange ratio. We further show that STAT3 controls S1PR1 expression in neurons via a positive feedback mechanism. Interestingly, several models of obesity and cancer anorexia display an imbalance of hypothalamic S1P/S1PR1/STAT3 axis, whereas pharmacological intervention ameliorates these phenotypes. Taken together, our data demonstrate that the neuronal S1P/S1PR1/STAT3 signalling axis plays a critical role in the control of energy homeostasis in rats.

Environmental Controls In The Water Use Patterns Of A Tropical Cloud Forest Tree Species, Drimys Brasiliensis (winteraceae).

Trees from tropical montane cloud forest (TMCF) display very dynamic patterns of water use. They are capable of downwards water transport towards the soil during leaf-wetting events, likely a consequence of foliar water uptake (FWU), as well as high rates of night-time transpiration (Enight) during drier nights. These two processes might represent important sources of water losses and gains to the plant, but little is known about the environmental factors controlling these water fluxes. We evaluated how contrasting atmospheric and soil water conditions control diurnal, nocturnal and seasonal dynamics of sap flow in Drimys brasiliensis (Miers), a common Neotropical cloud forest species. We monitored the seasonal variation of soil water content, micrometeorological conditions and sap flow of D. brasiliensis trees in the field during wet and dry seasons. We also conducted a greenhouse experiment exposing D. brasiliensis saplings under contrasting soil water conditions to deuterium-labelled fog water. We found that during the night D. brasiliensis possesses heightened stomatal sensitivity to soil drought and vapour pressure deficit, which reduces night-time water loss. Leaf-wetting events had a strong suppressive effect on tree transpiration (E). Foliar water uptake increased in magnitude with drier soil and during longer leaf-wetting events. The difference between diurnal and nocturnal stomatal behaviour in D. brasiliensis could be attributed to an optimization of carbon gain when leaves are dry, as well as minimization of nocturnal water loss. The leaf-wetting events on the other hand seem important to D. brasiliensis water balance, especially during soil droughts, both by suppressing tree transpiration (E) and as a small additional water supply through FWU. Our results suggest that decreases in leaf-wetting events in TMCF might increase D. brasiliensis water loss and decrease its water gains, which could compromise its ecophysiological performance and survival during dry periods.

A comparison of lower limb EMG and ground reaction forces between barefoot and shod gait in participants with diabetic neuropathic and healthy controls

Background: It is known that when barefoot, gait biomechanics of diabetic neuropathic patients differ from nondiabetic individuals. However, it is still unknown whether these biomechanical changes are also present during shod gait which is clinically advised for these patients. This study investigated the effect of the participants own shoes on gait biomechanics in diabetic neuropathic individuals compared to barefoot gait patterns and healthy controls. Methods: Ground reaction forces and lower limb EMG activities were analyzed in 21 non-diabetic adults (50.9 +/- 7.3 yr, 24.3 +/- 2.6 kg/m(2)) and 24 diabetic neuropathic participants (55.2 +/- 7.9 yr, 27.0 +/- 4.4 kg/m(2)). EMG patterns of vastus lateralis, lateral gastrocnemius and tibialis anterior, along with the vertical and antero-posterior ground reaction forces were studied during shod and barefoot gait. Results: Regardless of the disease, walking with shoes promoted an increase in the first peak vertical force and the peak horizontal propulsive force. Diabetic individuals had a delay in the lateral gastrocnemius EMG activity with no delay in the vastus lateralis. They also demonstrated a higher peak horizontal braking force walking with shoes compared to barefoot. Diabetic participants also had a smaller second peak vertical force in shod gait and a delay in the vastus lateralis EMG activity in barefoot gait compared to controls. Conclusions: The change in plantar sensory information that occurs when wearing shoes revealed a different motor strategy in diabetic individuals. Walking with shoes did not attenuate vertical forces in either group. Though changes in motor strategy were apparent, the biomechanical did not support the argument that the use of shoes contributes to altered motor responses during gait.

Psychogenetics of Turner syndrome: an investigation of 28 subjects and respective controls using the Bender test and Piagetian scales

Piagetian scales and the Bender visual motor gestalt test (BT) were applied to 28 subjects with universal 45, X Turner syndrome (TS), and their respective controls, in order to investigate their cognitive performance. Dermatoglyphics were also analyzed to obtain clues concerning embryological changes that may have appeared during development of the nervous system and could be associated with cognitive performance of TS patients. Dermatoglyphic pattern distribution was similar to that reported in previous studies of TS individuals: ulnar loops in the digital patterns and finger ridge, a-b, and A'-d counts were more frequent, while arch and whorl patterns were less frequent compared to controls. However, we did not find higher frequencies of hypothenar pattern, maximum atd angle, and ulnarity index in our TS subjects, unlike other investigations. Furthermore, we found significant differences between TS and control T line index values. The BT scores were also lower in probands, as has been previously reported, revealing a neurocognitive deficit of visual motor perception in TS individuals, which could be due to an absence of, or deficiency in, cerebral hemispheric lateralization. However, TS subjects seemed to improve their performance on BT with age. Cognitive performance of the TS subjects was not significantly different from that of controls, confirming a previous study in which TS performance was found to be similar to that of the normal Brazilian population. There were significant correlations between BT scores and Piagetian scale levels with dermatoglyphic parameters. This association could be explained by changes in the common ectodermal origin of the epidermis and the central nervous system. TS subjects seem to succeed in compensating their spatial impairments in adapting their cognitive and social contacts. We concluded that genetic counseling should consider cognitive and psychosocial difficulties presented by TS subjects, providing appropriate treatment and orientation for them and their families.

The Essential Nucleolar Yeast Protein Nop8p Controls the Exosome Function during 60S Ribosomal Subunit Maturation

The yeast nucleolar protein Nop8p has previously been shown to interact with Nip7p and to be required for 60S ribosomal subunit formation. Although depletion of Nop8p in yeast cells leads to premature degradation of rRNAs, the biochemical mechanism responsible for this phenotype is still not known. In this work, we show that the Nop8p amino-terminal region mediates interaction with the 5.8S rRNA, while its carboxyl-terminal portion interacts with Nip7p and can partially complement the growth defect of the conditional mutant strain Dnop8/GAL:NOP8. Interestingly, Nop8p mediates association of Nip7p to pre-ribosomal particles. Nop8p also interacts with the exosome subunit Rrp6p and inhibits the complex activity in vitro, suggesting that the decrease in 60S ribosomal subunit levels detected upon depletion of Nop8p may result from degradation of pre-rRNAs by the exosome. These results strongly indicate that Nop8p may control the exosome function during pre-rRNA processing.

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.

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.

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.