In an in vitro model of human tuberculosis, monocyte-microglial networks regulate matrix metalloproteinase-1 and -3 gene expression and secretion via a p38 mitogen activated protein kinase-dependent pathway.

BACKGROUND: Tuberculosis (TB) of the central nervous system (CNS) is characterized by extensive tissue inflammation, driven by molecules that cleave extracellular matrix such as matrix metalloproteinase (MMP)-1 and MMP-3. However, relatively little is known about the regulation of these MMPs in the CNS. METHODS: Using a cellular model of CNS TB, we stimulated a human microglial cell line (CHME3) with conditioned medium from Mycobacterium tuberculosis-infected primary human monocytes (CoMTb). MMP-1 and MMP-3 secretion was detected using ELISAs confirmed with casein zymography or western blotting. Key results of a phospho-array profile that detects a wide range of kinase activity were confirmed with phospho-Western blotting. Chemical inhibition (SB203580) of microglial cells allowed investigation of expression and secretion of MMP-1 and MMP-3. Finally we used promoter reporter assays employing full length and MMP-3 promoter deletion constructs. Student's t-test was used for comparison of continuous variables and multiple intervention experiments were compared by one-way ANOVA with Tukey's correction for multiple pairwise comparisons. RESULTS: CoMTb up-regulated microglial MMP-1 and MMP-3 secretion in a dose- and time-dependent manner. The phospho-array profiling showed that the major increase in kinase activity due to CoMTb stimulation was in p38 mitogen activated protein kinase (MAPK), principally the α and γ subunits. p38 phosphorylation was detected at 15 minutes, with a second peak of activity at 120 minutes. High basal extracellular signal-regulated kinase activity was further increased by CoMTb. Secretion and expression of MMP-1 and MMP-3 were both p38 dependent. CoMTb stimulation of full length and MMP-3 promoter deletion constructs demonstrated up-regulation of activity in the wild type but a suppression site between -2183 and -1612 bp. CONCLUSIONS: Monocyte-microglial network-dependent MMP-1 and MMP-3 gene expression and secretion are dependent upon p38 MAPK in tuberculosis. p38 is therefore a potential target for adjuvant therapy in CNS TB

The use of oral recombinant feline interferon omega in two cats with type II diabetes mellitus and concurrent feline chronic gingivostomatitis syndrome

Articles in International JournalsFeline Chronic Gingivostomatitis Syndrome (FCGS) is a common disease in clinical practice. Among the therapeutic options available, long-acting corticosteroids are frequently used due to their anti-inflammatory and immunosuppressive properties. Although they may improve the clinical symptoms, they can lead to a progressive form of the disease that becomes refractory to treatment. Furthermore, their direct relationship with type II diabetes mellitus (DM) is well known. Consequently, these drugs are controversial and not recommended for routine management of FCGS. Recombinant feline interferon-omega (rFeIFN-ω) is an immunomodulatory compound. Recently, its daily oral administration has been shown to be successful in treating refractory cases of FCGS. This case study describes two clinical cases of type II DM complicated by FCGS. Both animals were calicivirus positive and they had been previously treated with long-acting corticosteroids, which may have been the major cause of DM. The two cats were treated with glargine insulin (Lantus, starting dose 1 IU/cat twice daily (BID)), achieving remission 10 and 18 weeks later respectively. Considering the difficulty with control of FCGS in these animals, an oral daily dose of rFeIFN-ω was started as an alternative to long-acting corticosteroids. In both cats oral clinical signs gradually improved and 60 days after the start of therapy the owners reported a significant relief of pain during mastication. According to the authors’ knowledge, this is the first case report that describes the successful use of rFeIFN-ω in the management of FCGS in type II diabetic cats, in which long-acting corticosteroids are contraindicated

Prevalence of Disorders Recorded in Dogs Attending Primary-Care Veterinary Practices in England

Purebred dog health is thought to be compromised by an increasing occurence of inherited diseases but inadequate prevalence data on common disorders have hampered efforts to prioritise health reforms. Analysis of primary veterinary practice clinical data has been proposed for reliable estimation of disorder prevalence in dogs. Electronic patient record (EPR) data were collected on 148,741 dogs attending 93 clinics across central and south-eastern England. Analysis in detail of a random sample of EPRs relating to 3,884 dogs from 89 clinics identified the most frequently recorded disorders as otitis externa (prevalence 10.2%, 95% CI: 9.1-11.3), periodontal disease (9.3%, 95% CI: 8.3-10.3) and anal sac impaction (7.1%, 95% CI: 6.1-8.1). Using syndromic classification, the most prevalent body location affected was the head-and-neck (32.8%, 95% CI: 30.7-34.9), the most prevalent organ system affected was the integument (36.3%, 95% CI: 33.9-38.6) and the most prevalent pathophysiologic process diagnosed was inflammation (32.1%, 95% CI: 29.8-34.3). Among the twenty most-frequently recorded disorders, purebred dogs had a significantly higher prevalence compared with crossbreds for three: otitis externa (P = 0.001), obesity (P = 0.006) and skin mass lesion (P = 0.033), and popular breeds differed significantly from each other in their prevalence for five: periodontal disease (P = 0.002), overgrown nails (P = 0.004), degenerative joint disease (P = 0.005), obesity (P = 0.001) and lipoma (P = 0.003). These results fill a crucial data gap in disorder prevalence information and assist with disorder prioritisation. The results suggest that, for maximal impact, breeding reforms should target commonly-diagnosed complex disorders that are amenable to genetic improvement and should place special focus on at-risk breeds. Future studies evaluating disorder severity and duration will augment the usefulness of the disorder prevalence information reported herein

Cooperation and Contagion in Web-Based, Networked Public Goods Experiments

A longstanding idea in the literature on human cooperation is that cooperation should be reinforced when conditional cooperators are more likely to interact. In the context of social networks, this idea implies that cooperation should fare better in highly clustered networks such as cliques than in networks with low clustering such as random networks. To test this hypothesis, we conducted a series of web-based experiments, in which 24 individuals played a local public goods game arranged on one of five network topologies that varied between disconnected cliques and a random regular graph. In contrast with previous theoretical work, we found that network topology had no significant effect on average contributions. This result implies either that individuals are not conditional cooperators, or else that cooperation does not benefit from positive reinforcement between connected neighbors. We then tested both of these possibilities in two subsequent series of experiments in which artificial seed players were introduced, making either full or zero contributions. First, we found that although players did generally behave like conditional cooperators, they were as likely to decrease their contributions in response to low contributing neighbors as they were to increase their contributions in response to high contributing neighbors. Second, we found that positive effects of cooperation were contagious only to direct neighbors in the network. In total we report on 113 human subjects experiments, highlighting the speed, flexibility, and cost-effectiveness of web-based experiments over those conducted in physical labs

Postcopulatory sexual selection

The female reproductive tract is where competition between the sperm of different males takes place, aided and abetted by the female herself. Intense postcopulatory sexual selection fosters inter-sexual conflict and drives rapid evolutionary change to generate a startling diversity of morphological, behavioural and physiological adaptations. We identify three main issues that should be resolved to advance our understanding of postcopulatory sexual selection. We need to determine the genetic basis of different male fertility traits and female traits that mediate sperm selection; identify the genes or genomic regions that control these traits; and establish the coevolutionary trajectory of sexes

Formulation, characterisation and flexographic printing of novel Boger fluids to assess the effects of ink elasticity on print uniformity

Model elastic inks were formulated, rheologically characterised in shear and extension, and printed via flexography to assess the impact of ink elasticity on print uniformity. Flexography is a roll-to-roll printing process with great potential in the mass production of printed electronics for which understanding layer uniformity and the influence of rheology is of critical importance. A new set of flexo-printable Boger fluids was formulated by blending polyvinyl alcohol and high molecular weight polyacrylamide to provide inks of varying elasticity. During print trials, the phenomenon of viscous fingering was observed in all prints, with those of the Newtonian ink exhibiting a continuous striping in the printing direction. Increasing elasticity significantly influenced this continuity, disrupting it and leading to a quantifiable decrease in the overall relative size of the printed finger features. As such, ink elasticity was seen to have a profound effect on flexographic printing uniformity, showing the rheological tuning of inks may be a route to obtaining specific printed features

Incipient Social Groups: An Analysis via In-Vivo Behavioral Tracking

Social psychology is fundamentally the study of individuals in groups, yet there remain basic unanswered questions about group formation, structure, and change. We argue that the problem is methodological. Until recently, there was no way to track who was interacting with whom with anything approximating valid resolution and scale. In the current study we describe a new method that applies recent advances in image-based tracking to study incipient group formation and evolution with experimental precision and control. In this method, which we term "in vivo behavioral tracking," we track individuals' movements with a high definition video camera mounted atop a large field laboratory. We report results of an initial study that quantifies the composition, structure, and size of the incipient groups. We also apply in-vivo spatial tracking to study participants' tendency to cooperate as a function of their embeddedness in those crowds. We find that participants form groups of seven on average, are more likely to approach others of similar attractiveness and (to a lesser extent) gender, and that participants' gender and attractiveness are both associated with their proximity to the spatial center of groups (such that women and attractive individuals are more likely than men and unattractive individuals to end up in the center of their groups). Furthermore, participants' proximity to others early in the study predicted the effort they exerted in a subsequent cooperative task, suggesting that submergence in a crowd may predict social loafing. We conclude that in vivo behavioral tracking is a uniquely powerful new tool for answering longstanding, fundamental questions about group dynamics

Motives and comprehension in a public goods game with induced emotions

This study analyses the sensitivity of public goods contributions through the lens of psychological motives. We report the results of a public goods experiment in which subjects were induced with the motives of care and anger through autobiographical recall. Subjects' preferences, beliefs, and perceptions under each motive are compared with those of subjects experiencing a neutral autobiographical recall control condition. We find, but only for those subjects with the highest comprehension of the game, that care elicits significantly higher contributions than anger, with the control treatment in between. This positive influence of the care motive on unconditional giving is accounted for partly by preferences for giving and partly by the beliefs concerning greater contributions by others. Anger also affects attention to own and other's payoffs (using mouse tracking) and perceptions of the game's incentive structure (cooperative or competitive)

The deuteron: structure and form factors

A brief review of the history of the discovery of the deuteron in provided. The current status of both experiment and theory for the elastic electron scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic

Axelrod’s metanorm games on networks

Metanorms is a mechanism proposed to promote cooperation in social dilemmas. Recent experimental results show that network structures that underlie social interactions influence the emergence of norms that promote cooperation. We generalize Axelrod’s analysis of metanorms dynamics to interactions unfolding on networks through simulation and mathematical modeling. Network topology strongly influences the effectiveness of the metanorms mechanism in establishing cooperation. In particular, we find that average degree, clustering coefficient and the average number of triplets per node play key roles in sustaining or collapsing cooperationSpanish MICINN projects CSD2010-00034 (CONSOLIDER-INGENIO 2010) and DPI2010-16920, and by the Junta de Castilla y Leo´ n, references BU034A08 and GREX251-2009