Role of glutathionylation in infection and inflammation

Glutathionylation, that is, the formation of mixed disulfides between protein cysteines and glutathione (GSH) cysteines, is a reversible post-translational modification catalyzed by dierent cellular oxidoreductases, by which the redox state of the cell modulates protein function. So far, most studies on the identification of glutathionylated proteins have focused on cellular proteins, including proteins involved in host response to infection, but there is a growing number of reports showing that microbial proteins also undergo glutathionylation, with modification of their characteristics and functions. In the present review, we highlight the signaling role of GSH through glutathionylation, particularly focusing on microbial (viral and bacterial) glutathionylated proteins (GSSPs) and host GSSPs involved in the immune/inflammatory response to infection; moreover, we discuss the biological role of the process in microbial infections and related host responses

Adaptive Real-Time Scheduling for Legacy Multimedia Applications

Multimedia applications are often executed on standard Personal Computers. The absence of established standards has hindered the adoption of real-time scheduling solutions in this class of applications. Developers have adopted a wide range of heuristic approaches to achieve an acceptable timing behaviour but the result is often unreliable. We propose a mechanism to extend the benefits of real-time scheduling to legacy applications based on the combination of two techniques: 1) a real-time monitor that observes and infers the activation period of the application, and 2) a feedback mechanism that adapts the scheduling parameters to improve its real-time performance

W-CBS: A Scheduling Algorithm for Supporting QoS in IEEE 802.11e

This paper presents a new scheduling algorithm, the Wireless Constant Bandwidth Server (W-CBS) for the Access Points of an IEEE 802.11e wireless networks to support traffic streams with Quality of Service guarantees, in particular in the case of multimedia applications which present variable bit rate traffic. The performance of W-CBS is compared to that of the reference scheduler defined in 802.11e standard using the ns2 simulator. The results show that the W-CBS outperforms the reference scheduler with VBR traffic, in terms of resource utilization and maximum admitted flows

The Wizard of OS: a Heartbeat for Legacy Multimedia Applications

Multimedia applications are often characterised by implicit temporal constraints but, in many cases, they are not programmed using any specialised real-time API. These "Legacy applications" have no way to communicate their temporal constraints to the OS kernel, and their quality of service (QoS), being necessarily linked to the temporal behaviour, fails to satisfy acceptable standards. In this paper we propose an innovative way for dealing with these applications, based on the combination of an on-line identification mechanism (which extracts from high-level observations such important parameters as the execution rate) and an adaptive scheduler (specialised for legacy applications) that identifies the correct amount of CPU needed by each application. Preliminary experimental results are reported, proving the effectiveness of the proposed idea in providing a widely used multimedia player on Linux with appropriate QoS guarantees, through an appropriate choice of the scheduling parameters. Finally, a detailed road-map is presented with the possible extensions to the approach

Valutazione ecografica delle strutture ombelicali in vitelli frisoni nella prima settimana di vita

RIASSUNTO L’ecografia è ampiamente utilizzata in neonatologia veterinaria come ausilio diagnostico a numerose patologie, comprese le patologie ombelicali. Scopo del presente lavoro è stato quello di valutare ecograficamente le dimensioni delle strutture ombelicali in vitelli neonati clinicamente sani e di valutarne l’involuzione durante la prima settimana di vita. Sono stati inclusi 54 vitelli neonati di razza Frisona Italiana, nati presso la stalla il CIRAA dell’Università di Pisa. I criteri di inclusione sono stati: 1) fisiologica durata della gestazione (>260 giorni) e parto naturale; 2) APGAR score ≥7 valutato 5’ dopo la nascita; 3) clinicamente sani. La valutazione ecografica delle strutture ombelicali è stata eseguita 24 ore (T1), 3 (T3) e 7 (T7) giorni dopo la nascita con sonda convex di frequenza 5-7.5 MHz. I vitelli sono stati esaminati in posizione quadrupedale e mediante contenimento manuale. La vena ombelicale è stata visualizzata cranialmente al moncone ombelicale in scansione trasversale, sono stati valutati l’asse trasversale (MAT), l’asse longitudinale (MAL) e è stato calcolato il diametro medio della vena ombelicale (DMVO). Le arterie ombelicali sono state visualizzate a livello dell’apice della vescica, sono stati valutati il diametro dell’arteria di destra e di sinistra ed è stato calcolato il diametro medio della stessa (DMAO). I dati sono stati espressi come medie (X) e deviazioni standard (DS), è stato applicato il test di Kolmogorov-Smirnov per la valutazione della distribuzione dei dati. E’ stato eseguito il test ANOVA a una via per dati appaiati e il Tukey’s multiple comparison test come post hoc per la valutazione delle differenze fra le misure raccolte vs tempo. Sono state valutate differenze statisticamente significative per p<0,05. La MAT è stata 0,93±0,25 cm, 0,77±0,16 cm e 0,59±0,17 cm a T1, T3 e T7, rispettivamente. La MAL media è stata 1,37±0,29 cm, 1,09±0,27 cm e 0,71±0,20 cm a T1, T3 e T7, rispettivamente. La DMVO media è stata 1,07±0,23 cm, 0,85±0,24 cm and 0,57±0,14 cm a T1, T3 e T7, rispettivamente. Mentre la DMAO è stata 0,93±0,25 cm, 0,77±0,16 cm and 0,59±0,17 cm a T1, T3 e T7, rispettivamente. Il test ANOVA a una via ha mostrato differenze statisticamente significative per tutte le misure fra i tempi T1 vs T3, T1 vs T7 e T3 vs T7. Sono state sempre raccolte immagini ecografiche di ottima qualità con l’animale mantenuto in stazione quadrupedale e non rasato. L’analisi statistica ha evidenziato un’involuzione nelle strutture ombelicali nel vitello neonato, durante la prima settimana di vita, come già riportato in altre specie. SUMMARY Ultrasound evaluation is an important diagnostical tool in veterinary neonatology, used for diagnosis of many pathological conditions, including umbilical disorders. The aim of the present study was to determine ultrasonographically the size of the umbilical structures in clinically healthy newborn calves and to evaluate their involution during the first week of life. Fifty-four Italian Holstein Friesian newborn calves were included in this study. All the calves were born in the University dairy farm (CIRAA, Pisa). Inclusion criteria: 1) physiological gestational length (>260 days) and vaginal delivery; 2) APGAR score ≥7 within 5’ from birth; 3) no clinical symptoms revealed by clinical examination. The ultrasonographic examination of umbilical remnants was performed at 24 hours (T1), 3 (T3) and 7 (T7) days of life with a 5-7.5 Mhz convex transducer. Calves were in standing position, not sedated but only restricted manually. Umbilical vein was imaged just cranial to the umbilicus in trans-sectional scan, vertical (MAT) and horizontal (MAL) diameters were measured and a mean vein diameter (DMVO) was calculated. Arteries were visualised at the apex of the bladder, the diameter of right and left vessels was measured in trans-sectional scan, then a mean (DMAO) of the two measures was calculated. Data were expressed as mean (X) and standard deviation (SD). One-way ANOVA for paired data and Tukey’s multiple comparison test as a post hoc were performed to verify differences for measures vs time. Statistical differences were set at p<0,05. The mean MAT was 0,93±0,25 cm, 0,77±0,16 cm and 0,59±0,17 cm at T1, T3 and T7, respectively. The mean MAL was 1,37±0,29 cm, 1,09±0,27 cm and 0,71±0,20 cm at T1, T3 and T7, respectively. The mean DMVO was 1,07±0,23 cm, 0,85±0,24 cm and 0,57±0,14 cm at T1, T3 and T7, respectively. While the mean DMAO was 0,93±0,25 cm, 0,77±0,16 cm and 0,59±0,17 cm at T1, T3 and T7, respectively. One-way ANOVA test showed statistical differences for all measures between T1 vs T3, T1 vs T7 and T3 vs T7. A good quality imaging was reached with calves in standing position in no clipped areas. Our statistical results showed an involution of the umbilical vessels during the first week of life, as already reported in other species

Self-tuning Schedulers for Legacy Real-Time Applications

We present an approach for adaptive scheduling of soft real-time legacy applications (for which no timing information is exposed to the system). Our strategy is based on the combination of two techniques: 1) a real-time monitor that observes the sequence of events generated by the application to infer its activation period, 2) a feedback mechanism that adapts the scheduling parameters to ensure a timely execution of the application. By a thorough experimental evaluation of an implementation of our approach, we show its performance and its efficiency

Glutathione increase by the n-butanoyl glutathione derivative (GSH-C4) inhibits viral replication and induces a predominant Th1 immune profile in old mice infected with influenza virus

During aging, glutathione (GSH) content declines and the immune system undergoes a deficiency in the induction of Th1 response. Reduced secretion of Th1 cytokines, which is associated with GSH depletion, could weaken the host defenses against viral infections. We first evaluated the concentration of GSH and cysteine in organs of old mice; then, the effect of the administration of the N-butanoyl GSH derivative (GSH-C4) on the response of aged mice infected with influenza A PR8/H1N1 virus was studied through the determination of GSH concentration in organs, lung viral titer, IgA and IgG1/IgG2a production and Th1/Th2 cytokine profile. Old mice had lower GSH than young mice in organs. Also the gene expression of endoplasmic reticulum (ER) stress markers involved in GSH metabolism and folding of proteins, i.e. Nrf2 and PDI, was reduced. Following infection, GSH content remained low and neither infection nor GSH-C4 treatment affected Nrf2 expression. In contrast, PDI expression was upregulated during infection and appeared counterbalanced by GSH-C4. Moreover, the treatment with GSH-C4 increased GSH content in organs, reduced viral replication and induced a predominant Th1 response. In conclusion, GSH-C4 treatment could be used in the elderly to contrast influenza virus infection by inducing immune response, in particular the Th1 profile

Modular software architecture for flexible reservation mechanisms on heterogeneous resources

Management, allocation and scheduling of heterogeneous resources for complex distributed real-time applications is a chal- lenging problem. Timing constraints of applications may be fulfilled by a proper use of real-time scheduling policies, admission control and enforcement of timing constraints. However, it is not easy to design basic infrastructure services that allow for an easy access to the allocation of multiple heterogeneous resources in a distributed environment. In this paper, we present a middleware for providing distributed soft real-time applications with a uniform API for reserving heterogeneous resources with real-time scheduling capabilities in a distributed environment. The architecture relies on standard POSIX OS facilities, such as time management and standard TCP/IP networking services, and it is designed around CORBA, in order to facilitate modularity, flexibility and portability of the applications using it. However, real-time scheduling is supported by proper extensions at the kernel-level, plugged within the framework by means of dedicated resource managers. Our current implementation on Linux supports reservation of CPU, disk and network bandwidth. However, additional resource managers supporting alternative real-time schedulers for these resources, as well as additional types of resources, may be easily added. We present experimental results gathered on both synthetic applications and a real multimedia video streaming case study, showing advantages deriving from the use of the proposed middleware. Finally, overhead figures are reported, showing sustainability of the approach for a wide class of complex, distributed, soft real-time applications