Instrument Display Visual Angles for Conventional Aircraft and the MQ-9 Ground Control Station

Aircraft instrument panels should be designed such that primary displays are in optimal viewing location to minimize pilot perception and response time. Human Factors engineers define three zones (i.e. "cones") of visual location: 1) "Easy Eye Movement" (foveal vision); 2) "Maximum Eye Movement" (peripheral vision with saccades), and 3) "Head Movement" (head movement required). Instrument display visual angles were measured to determine how well conventional aircraft (T-34, T-38, F- 15B, F-16XL, F/A-18A, U-2D, ER-2, King Air, G-III, B-52H, DC-10, B747-SCA) and the MQ-9 ground control station (GCS) complied with these standards, and how they compared with each other. Methods: Selected instrument parameters included: attitude, pitch, bank, power, airspeed, altitude, vertical speed, heading, turn rate, slip/skid, AOA, flight path, latitude, longitude, course, bearing, range and time. Vertical and horizontal visual angles for each component were measured from the pilot s eye position in each system. Results: The vertical visual angles of displays in conventional aircraft lay within the cone of "Easy Eye Movement" for all but three of the parameters measured, and almost all of the horizontal visual angles fell within this range. All conventional vertical and horizontal visual angles lay within the cone of "Maximum Eye Movement". However, most instrument vertical visual angles of the MQ-9 GCS lay outside the cone of "Easy Eye Movement", though all were within the cone of "Maximum Eye Movement". All the horizontal visual angles for the MQ-9 GCS were within the cone of "Easy Eye Movement". Discussion: Most instrument displays in conventional aircraft lay within the cone of "Easy Eye Movement", though mission-critical instruments sometimes displaced less important instruments outside this area. Many of the MQ-9 GCS systems lay outside this area. Specific training for MQ-9 pilots may be needed to avoid increased response time and potential error during flight

Effects of whole-body vibration or resistive-vibration exercise on blood clotting and related biomarkers: a systematic review

Whole-body vibration (WBV) and resistive vibration exercise (RVE) are utilized as countermeasures against bone loss, muscle wasting, and physical deconditioning. The safety of the interventions, in terms of the risk of inducing undesired blood clotting and venous thrombosis, is not clear. We therefore performed the present systematic review of the available scientific literature on the issue. The review was conducted following the guidelines by the Space Biomedicine Systematic Review Group, based on Cochrane review guidelines. The relevant context or environment of the studies was “ground-based environment”; space analogs or diseased conditions were not included. The search retrieved 801 studies; 77 articles were selected for further consideration after an initial screening. Thirty-three studies met the inclusion criteria. The main variables related to blood markers involved angiogenic and endothelial factors, fibrinolysis and coagulation markers, cytokine levels, inflammatory and plasma oxidative stress markers. Functional and hemodynamic markers involved blood pressure measurements, systemic vascular resistance, blood flow and microvascular and endothelial functions. The available evidence suggests neutral or potentially positive effects of short- and long-term interventions with WBV and RVE on variables related to blood coagulation, fibrinolysis, inflammatory status, oxidative stress, cardiovascular, microvascular and endothelial functions. No significant warning signs towards an increased risk of undesired clotting and venous thrombosis were identified. If confirmed by further studies, WBV and RVE could be part of the countermeasures aimed at preventing or attenuating the muscular and cardiovascular deconditioning associated with spaceflights, permanence on planetary habitats and ground-based simulations of microgravity

Pathophysiology, risk, diagnosis, and management of venous thrombosis in space: where are we now?

The recent incidental discovery of an asymptomatic venous thrombosis (VT) in the internal jugular vein of an astronaut on the International Space Station prompted a necessary, immediate response from the space medicine community. The European Space Agency formed a topical team to review the pathophysiology, risk and clinical presentation of venous thrombosis and the evaluation of its prevention, diagnosis, mitigation, and management strategies in spaceflight. In this article, we discuss the findings of the ESA VT Topical Team over its 2-year term, report the key gaps as we see them in the above areas which are hindering understanding VT in space. We provide research recommendations in a stepwise manner that build upon existing resources, and highlight the initial steps required to enable further evaluation of this newly identified pertinent medical risk

Search for venous endothelial biomarkers heralding venous thromboembolism in space: a qualitative systematic review of terrestrial studies

Background: The recent discovery of a venous thrombosis in the internal jugular vein of an astronaut has highlighted the need to predict the risk of venous thromboembolism in otherwise healthy individuals (VTE) in space. Virchow's triad defines the three classic risk factors for VTE: blood stasis, hypercoagulability, and endothelial disruption/dysfunction. Among these risk factors, venous endothelial disruption/dysfunction remains incompletely understood, making it difficult to accurately predict risk, set up relevant prophylactic measures and initiate timely treatment of VTE, especially in an extreme environment. Methods: A qualitative systematic review focused on endothelial disruption/dysfunction was conducted following the guidelines produced by the Space Biomedicine Systematic Review Group, which are based on Cochrane review guidelines. We aimed to assess the venous endothelial biochemical and imaging markers that may predict increased risk of VTE during spaceflight by surveying the existing knowledge base surrounding these markers in analogous populations to astronauts on the ground. Results: Limited imaging markers related to endothelial dysfunction that were outside the bounds of routine clinical practice were identified. While multiple potential biomarkers were identified that may provide insight into the etiology of endothelial dysfunction and its link to future VTE, insufficient prospective evidence is available to formally recommend screening potential astronauts or healthy patients with any currently available novel biomarker. Conclusion: Our review highlights a critical knowledge gap regarding the role biomarkers of venous endothelial disruption have in predicting and identifying VTE. Future population-based prospective studies are required to link potential risk factors and biomarkers for venous endothelial dysfunction to occurrence of VTE

GPR50 Interacts with TIP60 to Modulate Glucocorticoid Receptor Signalling

GPR50 is an orphan G-protein coupled receptor most closely related to the melatonin receptors. The physiological function of GPR50 remains unclear, although our previous studies implicate the receptor in energy homeostasis. Here, we reveal a role for GPR50 as a signalling partner and modulator of the transcriptional co-activator TIP60. This interaction was identified in a yeast-two-hybrid screen, and confirmed by co-immunoprecipitation and co-localisation of TIP60 and GPR50 in HEK293 cells. Co-expression with TIP60 increased perinuclear localisation of full length GPR50, and resulted in nuclear translocation of the cytoplasmic tail of the receptor, suggesting a functional interaction of the two proteins. We further demonstrate that GPR50 can enhance TIP60-coactiavtion of glucocorticoid receptor (GR) signalling. In line with in vitro results, repression of pituitary Pomc expression, and induction of gluconeogenic genes in liver in response to the GR agonist, dexamethasone was attenuated in Gpr50−/− mice. These results identify a novel role for GPR50 in glucocorticoid receptor signalling through interaction with TIP60

Pathophysiology, risk, diagnosis, and management of venous thrombosis in space: where are we now?

The recent incidental discovery of an asymptomatic venous thrombosis (VT) in the internal jugular vein of an astronaut on the International Space Station prompted a necessary, immediate response from the space medicine community. The European Space Agency formed a topical team to review the pathophysiology, risk and clinical presentation of venous thrombosis and the evaluation of its prevention, diagnosis, mitigation, and management strategies in spaceflight. In this article, we discuss the findings of the ESA VT Topical Team over its 2-year term, report the key gaps as we see them in the above areas which are hindering understanding VT in space. We provide research recommendations in a stepwise manner that build upon existing resources, and highlight the initial steps required to enable further evaluation of this newly identified pertinent medical risk

Recruitment and Activation of RSK2 by HIV-1 Tat

The transcriptional activity of the integrated HIV provirus is dependent on the chromatin organization of the viral promoter and the transactivator Tat. Tat recruits the cellular pTEFb complex and interacts with several chromatin-modifying enzymes, including the histone acetyltransferases p300 and PCAF. Here, we examined the interaction of Tat with activation-dependent histone kinases, including the p90 ribosomal S6 kinase 2 (RSK2). Dominant-negative RSK2 and treatment with a small-molecule inhibitor of RSK2 kinase activity inhibited the transcriptional activity of Tat, indicating that RSK2 is important for Tat function. Reconstitution of RSK2 in cells from subjects with a genetic defect in RSK2 expression (Coffin-Lowry syndrome) enhanced Tat transactivation. Tat interacted with RSK2 and activated RSK2 kinase activity in cells. Both properties were lost in a mutant Tat protein (F38A) that is deficient in HIV transactivation. Our data identify a novel reciprocal regulation of Tat and RSK2 function, which might serve to induce early changes in the chromatin organization of the HIV LTR

HIV-1 Tat and AIDS-associated cancer: targeting the cellular anti-cancer barrier?

The acquired immunodeficiency syndrome (AIDS) is accompanied by a significant increase in the incidence of neoplasms. Several causative agents have been proposed for this phenomenon. These include immunodeficiency and oncogenic DNA viruses and the HIV-1 protein Tat. Cancer in general is closely linked to genomic instability and DNA repair mechanisms. The latter maintains genomic stability and serves as a cellular anti-cancer barrier. Defects in DNA repair pathway are associated with carcinogenesis

Function of the Active Site Lysine Autoacetylation in Tip60 Catalysis

The 60-kDa HIV-Tat interactive protein (Tip60) is a key member of the MYST family of histone acetyltransferases (HATs) that plays critical roles in multiple cellular processes. We report here that Tip60 undergoes autoacetylation at several lysine residues, including a key lysine residue (i.e. Lys-327) in the active site of the MYST domain. The mutation of K327 to arginine led to loss of both the autoacetylation activity and the cognate HAT activity. Interestingly, deacetylated Tip60 still kept a substantial degree of HAT activity. We also investigated the effect of cysteine 369 and glutamate 403 in Tip60 autoacetylation in order to understand the molecular pathway of the autoacetylation at K327. Together, we conclude that the acetylation of K327 which is located in the active site of Tip60 regulates but is not obligatory for the catalytic activity of Tip60. Since acetylation at this key residue appears to be evolutionarily conserved amongst all MYST proteins, our findings provide an interesting insight into the regulatory mechanism of MYST activities

In vitro nuclear interactome of the HIV-1 Tat protein

<p>Abstract</p> <p>Background</p> <p>One facet of the complexity underlying the biology of HIV-1 resides not only in its limited number of viral proteins, but in the extensive repertoire of cellular proteins they interact with and their higher-order assembly. HIV-1 encodes the regulatory protein Tat (86–101aa), which is essential for HIV-1 replication and primarily orchestrates HIV-1 provirus transcriptional regulation. Previous studies have demonstrated that Tat function is highly dependent on specific interactions with a range of cellular proteins. However they can only partially account for the intricate molecular mechanisms underlying the dynamics of proviral gene expression. To obtain a comprehensive nuclear interaction map of Tat in T-cells, we have designed a proteomic strategy based on affinity chromatography coupled with mass spectrometry.</p> <p>Results</p> <p>Our approach resulted in the identification of a total of 183 candidates as Tat nuclear partners, 90% of which have not been previously characterised. Subsequently we applied <it>in silico </it>analysis, to validate and characterise our dataset which revealed that the Tat nuclear interactome exhibits unique signature(s). First, motif composition analysis highlighted that our dataset is enriched for domains mediating protein, RNA and DNA interactions, and helicase and ATPase activities. Secondly, functional classification and network reconstruction clearly depicted Tat as a polyvalent protein adaptor and positioned Tat at the nexus of a densely interconnected interaction network involved in a range of biological processes which included gene expression regulation, RNA biogenesis, chromatin structure, chromosome organisation, DNA replication and nuclear architecture.</p> <p>Conclusion</p> <p>We have completed the <it>in vitro </it>Tat nuclear interactome and have highlighted its modular network properties and particularly those involved in the coordination of gene expression by Tat. Ultimately, the highly specialised set of molecular interactions identified will provide a framework to further advance our understanding of the mechanisms of HIV-1 proviral gene silencing and activation.</p