Regulation of NKG2D-Dependent NK Cell Functions: The Yin and the Yang of Receptor Endocytosis.

Natural-killer receptor group 2, member D (NKG2D) is a well characterized natural killer (NK) cell activating receptor that recognizes several ligands poorly expressed on healthy cells but up-regulated upon stressing stimuli in the context of cancer or viral infection. Although NKG2D ligands represent danger signals that render target cells more susceptible to NK cell lysis, accumulating evidence demonstrates that persistent exposure to ligand-expressing cells causes the decrease of NKG2D surface expression leading to a functional impairment of NKG2D-dependent NK cell functions. Upon ligand binding, NKG2D is internalized from the plasma membrane and sorted to lysosomes for degradation. However, receptor endocytosis is not only a mechanism of receptor clearance from the cell surface, but is also required for the proper activation of signalling events leading to the functional program of NK cells. This review is aimed at providing a summary of current literature relevant to the molecular mechanisms leading to NKG2D down-modulation with particular emphasis given to the role of NKG2D endocytosis in both receptor degradation and signal propagation. Examples of chronic ligand-induced down-regulation of NK cell activating receptors other than NKG2D, including natural cytotoxicity receptors (NCRs), DNAX accessory molecule-1 (DNAM1) and CD16, will be also discussed

Correlation of Impedance and Effective Electrode Area of Iridium Oxide Neural Electrodes

Iridium oxide is routinely used for bionic applications owing to its high charge injection capacity. The electrode impedance at 1 kHz is typically reported to predict neural recording performance. In this article, the impedance of activated iridium oxide films (AIROFs) has been examined. The impedance of unactivated iridium electrodes was half that of platinum electrodes of similar geometry, indicating some iridium oxide was present on the electrode surface. A two time constant equivalent circuit was used to model the impedance of activated iridium. The impedance at low and intermediate frequencies decreased with increasing number of activation pulses and total activation charge. The impedance at 12 Hz correlated with the steady-state diffusion electroactive area. The impedance at 12 Hz also correlated with the charge density of the electrode. The high charge density and low impedance of AIROFs may provide improved neural stimulation and recording properties compared with typically used platinum electrodes

Predicting neural recording performance of implantable electrodes

Recordings of neural activity can be used to aid communication, control prosthetic devices or alleviatedisease symptoms. Chronic recordings require a high signal-to-noise ratio that is stable for years. Currentcortical devices generally fail within months to years after implantation. Development of novel devices toincrease lifetime requires valid testing protocols and a knowledge of the critical parameters controllingelectrophysiological performance. Here we present electrochemical and electrophysiological protocolsfor assessing implantable electrodes. Biological noise from neural recording has significant impact on signal-to-noise ratio. A recently developed surgical approach was utilised to reduce biological noise. This allowed correlation of electrochemical and electrophysiological behaviour. The impedance versus frequency of modified electrodes was non-linear. It was found that impedance at low frequencies was astronger predictor of electrophysiological performance than the typically reported impedance at 1 kHz.Low frequency impedance is a function of electrode area, and a strong correlation of electrode area with electrophysiological response was also seen. Use of these standardised testing protocols will allow future devices to be compared before transfer to preclinical and clinical trials

Detection of bovine papillomavirus type 2 in the peripheral blood of cattle with urinary bladder tumours: possible biological role

Bovine papillomavirus type 2 (BPV-2) infection has been associated with urinary bladder tumours in adult cattle grazing on bracken fern-infested land. In this study, we investigated the simultaneous presence of BPV-2 in whole blood and urinary bladder tumours of adult cattle in an attempt to better understand the biological role of circulating BPV-2. Peripheral blood samples were collected from 78 cattle clinically suffering from a severe chronic enzootic haematuria. Circulating BPV-2 DNA was detected in 61 of them and in two blood samples from healthy cows. Fifty of the affected animals were slaughtered at public slaughterhouses and neoplastic proliferations in the urinary bladder were detected in all of them. BPV-2 DNA was amplified and sequenced in 78% of urinary bladder tumour samples and in 38.9% of normal samples as a control. Circulating episomal BPV-2 DNA was detected in 78.2% of the blood samples. Simultaneous presence of BPV-2 DNA in neoplastic bladder and blood samples was detected in 37 animals. Specific viral E5 mRNA and E5 oncoprotein were also detected in blood by RT-PCR and Western blot/immunocytochemistry, respectively. It is likely that BPV-2 can persist and be maintained in an active status in the bloodstream, in particular in the lymphocytes, as a reservoir of viral infection that, in the presence of co-carcinogens, may cause the development of urinary bladder tumours

Application of biological growth risk models to the management of built heritage

La qualità degli spazi interni è fortemente legata alle condizioni igrotermiche che influenzano il comfort degli utenti e i rischi di conservazione del patrimonio edilizio. Inoltre, una gestione incurante di spazi espositivi con numerosi accessi può causare carichi eccessivi di umidità, e conseguenti fenomeni di degrado. In questo lavoro, è stata considerata una sala espositiva rappresentativa del patrimonio costruito. Il rischio di proliferazione biologica è indagato nelle condizioni climatiche di Milano e Barcellona, con diversi ratei di ventilazione e numero di visitatori. I risultati delineano la necessità di politiche informate da analisi avanzate per prevenire il rischio igrotermico, in assenza di impianti, che non è sempre possibile integrare nel patrimonio edilizio storico.The quality of the interior spaces is strongly related to the hygro-thermal conditions which affect the users’ comfort, and may yield to preservation risk for the built heritage. Moreover, careless management of exposition spaces with excessive occupancy may result in moisture loads that promote degradation. In this paper, as a case study, an exposition hall representative of the built heritage is considered. The microbiological growth risk is investigated at two different climate conditions, namely Milan and Barcelona, considering varying ventilation rates and number of visitors. The results outline the need of policies informed by advanced analyses to prevent hygro-thermal risk in the absence of dedicated building services, that cannot always be integrated in built heritage

Elemental and isotopic profiling: a tool for distinguishing the botanical origin of oenological tannins

Much contemporary evidence underscores the pathophysiological importance of Ca2+ handling by acidic organelles such as lysosomes. Whereas our knowledge of how Ca2+ is released from these acidic Ca2+ stores (the ‘outs’) is advancing, we know relatively little about how Ca2+ uptake is effected (the ‘ins’). Here I highlight new work identifying animal Ca2+/H+ (CAX) exchangers that localize to acidic organelles, mediate Ca2+ uptake and regulate cell migration in vivo. Continued molecular definition of the acidic Ca2+ store toolkit provides new insight into Ca2+-dependent function