Multiple dynamical time-scales in networks with hierarchically nested modular organization

Many natural and engineered complex networks have intricate mesoscopic organization, e.g., the clustering of the constituent nodes into several communities or modules. Often, such modularity is manifested at several different hierarchical levels, where the clusters defined at one level appear as elementary entities at the next higher level. Using a simple model of a hierarchical modular network, we show that such a topological structure gives rise to characteristic time-scale separation between dynamics occurring at different levels of the hierarchy. This generalizes our earlier result for simple modular networks, where fast intra-modular and slow inter-modular processes were clearly distinguished. Investigating the process of synchronization of oscillators in a hierarchical modular network, we show the existence of as many distinct time-scales as there are hierarchical levels in the system. This suggests a possible functional role of such mesoscopic organization principle in natural systems, viz., in the dynamical separation of events occurring at different spatial scales.Comment: 10 pages, 4 figure

Stressor- and Corticotropin releasing Factor-induced Reinstatement and Active Stress-related Behavioral Responses are Augmented Following Long-access Cocaine Self-administration by Rats

Rationale Stressful events during periods of drug abstinence likely contribute to relapse in cocaine-dependent individuals. Excessive cocaine use may increase susceptibility to stressor-induced relapse through alterations in brain corticotropin-releasing factor (CRF) responsiveness. Objectives This study examined stressor- and CRF-induced cocaine seeking and other stress-related behaviors in rats with different histories of cocaine self-administration (SA). Materials and methods Rats self-administered cocaine under short-access (ShA; 2 h daily) or long-access (LgA; 6 h daily) conditions for 14 days or were provided access to saline and were tested for reinstatement by a stressor (electric footshock), cocaine or an icv injection of CRF and for behavioral responsiveness on the elevated plus maze, in a novel environment and in the light–dark box after a 14- to 17-day extinction/withdrawal period. Results LgA rats showed escalating patterns of cocaine SA and were more susceptible to reinstatement by cocaine, EFS, or icv CRF than ShA rats. Overall, cocaine SA increased activity in the center field of a novel environment, on the open arms of the elevated plus maze, and in the light compartment of a light–dark box. In most cases, the effects of cocaine SA were dependent on the pattern/amount of cocaine intake with statistically significant differences from saline self-administering controls only observed in LgA rats. Conclusions When examined after several weeks of extinction/ withdrawal, cocaine SA promotes a more active pattern of behavior during times of stress that is associated with a heightened susceptibility to stressor-induced cocaine-seeking behavior and may be the consequence of augmented CRF regulation of addiction-related neurocircuitry

Ultraviolet radiation and cyanobacteria.

Cyanobacteria are the dominant photosynthetic prokaryotes from an ecological, economical, or evolutionary perspective, and depend on solar energy to conduct their normal life processes. However, the marked increase in solar ultraviolet radiation (UVR) caused by the continuous depletion of the stratospheric ozone shield has fueled serious concerns about the ecological consequences for all living organisms, including cyanobacteria. UV-B radiation can damage cellular DNA and several physiological and biochemical processes in cyanobacterial cells, either directly, through its interaction with certain biomolecules that absorb in the UV range, or indirectly, with the oxidative stress exerted by reactive oxygen species. However, cyanobacteria have a long history of survival on Earth, and they predate the existence of the present ozone shield. To withstand the detrimental effects of solar UVR, these prokaryotes have evolved several lines of defense and various tolerance mechanisms, including avoidance, antioxidant production, DNA repair, protein resynthesis, programmed cell death, and the synthesis of UV-absorbing/screening compounds, such as mycosporine-like amino acids (MAAs) and scytonemin. This study critically reviews the current information on the effects of UVR on several physiological and biochemical processes of cyanobacteria and the various tolerance mechanisms they have developed. Genomic insights into the biosynthesis of MAAs and scytonemin and recent advances in our understanding of the roles of exopolysaccharides and heat shock proteins in photoprotection are also discussed

Hematological Changes in Women and Infants Exposed to an AZT-Containing Regimen for Prevention of Mother-to-child-transmission of HIV in Tanzania.

Tanzanian guidelines for prevention of mother-to-child-transmission of HIV (PMTCT) recommend an antiretroviral combination regimen involving zidovudine (AZT) during pregnancy, single-dosed nevirapine at labor onset, AZT plus Lamivudine (3TC) during delivery, and AZT/3TC for 1-4 weeks postpartum. As drug toxicities are a relevant concern, we assessed hematological alterations in AZT-exposed women and their infants. A cohort of HIV-positive women, either with AZT intake (n = 82, group 1) or without AZT intake (n = 62, group 2) for PMTCT during pregnancy, was established at Kyela District Hospital, Tanzania. The cohort also included the infants of group 1 with an in-utero AZT exposure ≥4 weeks, receiving AZT for 1 week postpartum (n = 41), and infants of group 2 without in-utero AZT exposure, receiving a prolonged 4-week AZT tail (n = 58). Complete blood counts were evaluated during pregnancy, birth, weeks 4-6 and 12. For women of group 1 with antenatal AZT intake, we found a statistically significant decrease in hemoglobin level, red blood cells, white blood cells, granulocytes, as well as an increase in red cell distribution width and platelet count. At delivery, the median red blood cell count was significantly lower and the median platelet count was significantly higher in women of group 1 compared to group 2. At birth, infants from group 1 showed a lower median hemoglobin level and granulocyte count and a higher frequency of anemia and granulocytopenia. At 4-6 weeks postpartum, the mean neutrophil granulocyte count was significantly lower and neutropenia was significantly more frequent in infants of group 2. AZT exposure during pregnancy as well as after birth resulted in significant hematological alterations for women and their newborns, although these changes were mostly mild and transient in nature. Research involving larger cohorts is needed to further analyze the impact of AZT-containing regimens on maternal and infant health

The selective phosphodiesterase 4 inhibitor roflumilast and phosphodiesterase 3/4 inhibitor pumafentrine reduce clinical score and TNF expression in experimental colitis in mice.

The specific inhibition of phosphodiesterase (PDE)4 and dual inhibition of PDE3 and PDE4 has been shown to decrease inflammation by suppression of pro-inflammatory cytokine synthesis. We examined the effect of roflumilast, a selective PDE4 inhibitor marketed for severe COPD, and the investigational compound pumafentrine, a dual PDE3/PDE4 inhibitor, in the preventive dextran sodium sulfate (DSS)-induced colitis model. The clinical score, colon length, histologic score and colon cytokine production from mice with DSS-induced colitis (3.5% DSS in drinking water for 11 days) receiving either roflumilast (1 or 5 mg/kg body weight/d p.o.) or pumafentrine (1.5 or 5 mg/kg/d p.o.) were determined and compared to vehicle treated control mice. In the pumafentrine-treated animals, splenocytes were analyzed for interferon-γ (IFNγ) production and CD69 expression. Roflumilast treatment resulted in dose-dependent improvements of clinical score (weight loss, stool consistency and bleeding), colon length, and local tumor necrosis factor-α (TNFα) production in the colonic tissue. These findings, however, were not associated with an improvement of the histologic score. Administration of pumafentrine at 5 mg/kg/d alleviated the clinical score, the colon length shortening, and local TNFα production. In vitro stimulated splenocytes after in vivo treatment with pumafentrine showed a significantly lower state of activation and production of IFNγ compared to no treatment in vivo. These series of experiments document the ameliorating effect of roflumilast and pumafentrine on the clinical score and TNF expression of experimental colitis in mice

Pituitary apoplexy following shoulder arthroplasty: a case report

<p>Abstract</p> <p>Introduction</p> <p>Pituitary apoplexy following a major surgical procedure is a catastrophic event and the diagnosis can be delayed in a previously asymptomatic patient. The decision on thromboprophylaxis in shoulder replacements in the absence of definite guidelines, rests on a careful clinical judgment.</p> <p>Case presentation</p> <p>A previously healthy 62-year-old Caucasian male patient who underwent shoulder arthroplasty developed hyponatremia resistant to correction with saline replacement. The patient had a positive family history of deep vein thrombosis and pulmonary embolism and heparin thromboprophylaxis was considered on clinical grounds. The patient developed hyponatremia resistant to conventional treatment and later developed ocular localizing signs with oculomotor nerve palsy. The diagnosis was delayed due to other confounding factors in the immediate post-operative period. Subsequent workup confirmed a pituitary adenoma with features of pituitary insufficiency. The patient was managed successfully on conservative lines with a multidisciplinary approach.</p> <p>Conclusions</p> <p>A high index of suspicion is required in the presence of isolated post-operative hyponatremia resistant to medical correction. A central cause, in particular pituitary adenoma, should be suspected early. Thromboprophylaxis in shoulder replacements needs careful consideration as it may be a contributory factor in precipitating this life-threatening condition.</p

Emergence of scale-free leadership structure in social recommender systems

The study of the organization of social networks is important for understanding of opinion formation, rumor spreading, and the emergence of trends and fashion. This paper reports empirical analysis of networks extracted from four leading sites with social functionality (Delicious, Flickr, Twitter and YouTube) and shows that they all display a scale-free leadership structure. To reproduce this feature, we propose an adaptive network model driven by social recommending. Artificial agent-based simulations of this model highlight a "good get richer" mechanism where users with broad interests and good judgments are likely to become popular leaders for the others. Simulations also indicate that the studied social recommendation mechanism can gradually improve the user experience by adapting to tastes of its users. Finally we outline implications for real online resource-sharing systems

Deletion of the GABAA α2-subunit does not alter self dministration of cocaine or reinstatement of cocaine seeking

Rationale GABAA receptors containing α2-subunits are highly represented in brain areas that are involved in motivation and reward, and have been associated with addiction to several drugs, including cocaine. We have shown previously that a deletion of the α2-subunit results in an absence of sensitisation to cocaine. Objective We investigated the reinforcing properties of cocaine in GABAA α2-subunit knockout (KO) mice using an intravenous self-administration procedure. Methods α2-subunit wildtype (WT), heterozygous (HT) and KO mice were trained to lever press for a 30 % condensed milk solution. After implantation with a jugular catheter, mice were trained to lever press for cocaine (0.5 mg/kg/infusion) during ten daily sessions. Responding was extinguished and the mice tested for cue- and cocaine-primed reinstatement. Separate groups of mice were trained to respond for decreasing doses of cocaine (0.25, 0.125, 0.06 and 0.03 mg/kg). Results No differences were found in acquisition of lever pressing for milk. All genotypes acquired self-administration of cocaine and did not differ in rates of self-administration, dose dependency or reinstatement. However, whilst WT and HT mice showed a dose-dependent increase in lever pressing during the cue presentation, KO mice did not. Conclusions Despite a reported absence of sensitisation, motivation to obtain cocaine remains unchanged in KO and HT mice. Reinstatement of cocaine seeking by cocaine and cocaine-paired cues is also unaffected. We postulate that whilst not directly involved in reward perception, the α2-subunit may be involved in modulating the “energising” aspect of cocaine’s effects on reward-seeking

The effect of initial local anesthetic dose with continuous interscalene analgesia on postoperative pain and diaphragmatic function in patients undergoing arthroscopic shoulder surgery: a double-blind, randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Interscalene block (ISB) is commonly performed using 20-40 mL of local anesthetic. Spread to adjacent structures and consequent adverse effects including paralysis of the ipsilateral hemidiaphragm are frequent. Pain ratings, analgesic requirements, adverse events, satisfaction, function and diaphragmatic excursion were compared following interscalene block (ISB) with reduced initial bolus volumes.</p> <p>Methods</p> <p>Subjects undergoing arthroscopic rotator cuff repair were randomized to receive 5, 10, or 20 mL ropivacaine 0.75% for ISB in a double-blind fashion (N = 36). Continuous infusion with ropivacaine 0.2% was maintained for 48 h. Pain and diaphragmatic excursion were assessed before block and in the recovery unit.</p> <p>Results</p> <p>Pain ratings in the recovery room were generally less than 4 (0-10 NRS) for all treatment groups, but a statistically significant difference was noted between the 5 and 20 mL groups (NRS: 2.67 vs. 0.62 respectively; p = 0.04). Pain ratings and supplemental analgesic use were similar among the groups at 24 h, 48 h and 12 weeks. There were no differences in the quality of block for surgical anesthesia. Dyspnea was significantly greater in the 20 mL group (p = 0.041). Subjects with dyspnea had significant diaphragmatic impairment more frequently (Relative risk: 2.5; 95%CI: 1.3-4.8; p = 0.042). Increased contralateral diaphragmatic motion was measured in 29 of the 36 subjects. Physical shoulder function at 12 weeks improved over baseline in all groups (baseline mean SST: 6.3, SEM: 0.6; 95%CI: 5.1-7.5; 12 week mean SST: 8.2, SEM: 0.46; 95%CI: 7.3-9.2; p = 0.0035).</p> <p>Conclusions</p> <p>ISB provided reliable surgical analgesia with 5 mL, 10 mL or 20 mL ropivacaine (0.75%). The 20 mL volume was associated with increased complaints of dyspnea. The 5 mL volume was associated with statistically higher pain scores in the immediate postoperative period. Lower volumes resulted in a reduced incidence of dyspnea compared to 20 mL, however diaphragmatic impairment was not eliminated. Compensatory increases in contralateral diaphragmatic movement may explain tolerance for ipsilateral paresis.</p> <p>Trial Registration</p> <p>clinicaltrials.gov. identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00672100">NCT00672100</a></p

A particle swarm optimization-based algorithm for finding gapped motifs

<p>Abstract</p> <p>Background</p> <p>Identifying approximately repeated patterns, or motifs, in DNA sequences from a set of co-regulated genes is an important step towards deciphering the complex gene regulatory networks and understanding gene functions.</p> <p>Results</p> <p>In this work, we develop a novel motif finding algorithm (PSO+) using a population-based stochastic optimization technique called Particle Swarm Optimization (PSO), which has been shown to be effective in optimizing difficult multidimensional problems in continuous domains. We propose a modification of the standard PSO algorithm to handle discrete values, such as characters in DNA sequences. The algorithm provides several features. First, we use both consensus and position-specific weight matrix representations in our algorithm, taking advantage of the efficiency of the former and the accuracy of the latter. Furthermore, many real motifs contain gaps, but the existing methods usually ignore them or assume a user know their exact locations and lengths, which is usually impractical for real applications. In comparison, our method models gaps explicitly, and provides an easy solution to find gapped motifs without any detailed knowledge of gaps. Our method allows the presence of input sequences containing zero or multiple binding sites.</p> <p>Conclusion</p> <p>Experimental results on synthetic challenge problems as well as real biological sequences show that our method is both more efficient and more accurate than several existing algorithms, especially when gaps are present in the motifs.</p