TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members

TNF receptor 1 signaling induces NF-κB activation and necroptosis in L929 cells. We previously reported that cellular inhibitor of apoptosis protein-mediated receptor-interacting protein 1 (RIP1) ubiquitination acts as a cytoprotective mechanism, whereas knockdown of cylindromatosis, a RIP1-deubiquitinating enzyme, protects against tumor necrosis factor (TNF)-induced necroptosis. We report here that RIP1 is a crucial mediator of canonical NF-κB activation in L929 cells, therefore questioning the relative cytoprotective contribution of RIP1 ubiquitination versus canonical NF-κB activation. We found that attenuated NF-κB activation has no impact on TNF-induced necroptosis. However, we identified A20 and linear ubiquitin chain assembly complex as negative regulators of necroptosis. Unexpectedly, and in contrast to RIP3, we also found that knockdown of RIP1 did not block TNF cytotoxicity. Cell death typing revealed that RIP1-depleted cells switch from necroptotic to apoptotic death, indicating that RIP1 can also suppress apoptosis in L929 cells. Inversely, we observed that Fas-associated protein via a death domain, cellular FLICE inhibitory protein and caspase-8, which are all involved in the initiation of apoptosis, counteract necroptosis induction. Finally, we also report RIP1-independent but RIP3-mediated necroptosis in the context of TNF signaling in particular conditions

Sympatric woodland Myotis bats form tight-knit social groups with exclusive roost home ranges

Background: The structuring of wild animal populations can influence population dynamics, disease spread, and information transfer. Social network analysis potentially offers insights into these processes but is rarely, if ever, used to investigate more than one species in a community. We therefore compared the social, temporal and spatial networks of sympatric Myotis bats (M. nattereri (Natterer's bats) and M. daubentonii (Daubenton's bats)), and asked: (1) are there long-lasting social associations within species? (2) do the ranges occupied by roosting social groups overlap within or between species? (3) are M. daubentonii bachelor colonies excluded from roosting in areas used by maternity groups? Results: Using data on 490 ringed M. nattereri and 978 M. daubentonii from 379 colonies, we found that both species formed stable social groups encompassing multiple colonies. M. nattereri formed 11 mixed-sex social groups with few (4.3%) inter-group associations. Approximately half of all M. nattereri were associated with the same individuals when recaptured, with many associations being long-term (>100 days). In contrast, M. daubentonii were sexually segregated; only a quarter of pairs were associated at recapture after a few days, and inter-sex associations were not long-lasting. Social groups of M. nattereri and female M. daubentonii had small roost home ranges (mean 0.2 km2 in each case). Intra-specific overlap was low, but inter-specific overlap was high, suggesting territoriality within but not between species. M. daubentonii bachelor colonies did not appear to be excluded from roosting areas used by females. Conclusions: Our data suggest marked species- and sex-specific patterns of disease and information transmission are likely between bats of the same genus despite sharing a common habitat. The clear partitioning of the woodland amongst social groups, and their apparent reliance on small patches of habitat for roosting, means that localised woodland management may be more important to bat conservation than previously recognised

Comparison of the Airtraq® and Truview® laryngoscopes to the Macintosh laryngoscope for use by Advanced Paramedics in easy and simulated difficult intubation in manikins

<p>Abstract</p> <p>Background</p> <p>Paramedics are frequently required to perform tracheal intubation, a potentially life-saving manoeuvre in severely ill patients, in the prehospital setting. However, direct laryngoscopy is often more difficult in this environment, and failed tracheal intubation constitutes an important cause of morbidity. Novel indirect laryngoscopes, such as the Airtraq^®and Truview^®laryngoscopes may reduce this risk.</p> <p>Methods</p> <p>We compared the efficacy of these devices to the Macintosh laryngoscope when used by 21 Paramedics proficient in direct laryngoscopy, in a randomized, controlled, manikin study. Following brief didactic instruction with the Airtraq^®and Truview^®laryngoscopes, each participant took turns performing laryngoscopy and intubation with each device, in an easy intubation scenario and following placement of a hard cervical collar, in a SimMan^®manikin.</p> <p>Results</p> <p>The Airtraq^®reduced the number of optimization manoeuvres and reduced the potential for dental trauma when compared to the Macintosh, in both the normal and simulated difficult intubation scenarios. In contrast, the Truview^®increased the duration of intubation attempts, and required a greater number of optimization manoeuvres, compared to both the Macintosh and Airtraq^®devices.</p> <p>Conclusion</p> <p>The Airtraq^®laryngoscope performed more favourably than the Macintosh and Truview^®devices when used by Paramedics in this manikin study. Further studies are required to extend these findings to the clinical setting.</p

Comparison of the Airtraq® and Truview® laryngoscopes to the Macintosh laryngoscope for use by Advanced Paramedics in easy and simulated difficult intubation in manikins

<p>Abstract</p> <p>Background</p> <p>Paramedics are frequently required to perform tracheal intubation, a potentially life-saving manoeuvre in severely ill patients, in the prehospital setting. However, direct laryngoscopy is often more difficult in this environment, and failed tracheal intubation constitutes an important cause of morbidity. Novel indirect laryngoscopes, such as the Airtraq^®and Truview^®laryngoscopes may reduce this risk.</p> <p>Methods</p> <p>We compared the efficacy of these devices to the Macintosh laryngoscope when used by 21 Paramedics proficient in direct laryngoscopy, in a randomized, controlled, manikin study. Following brief didactic instruction with the Airtraq^®and Truview^®laryngoscopes, each participant took turns performing laryngoscopy and intubation with each device, in an easy intubation scenario and following placement of a hard cervical collar, in a SimMan^®manikin.</p> <p>Results</p> <p>The Airtraq^®reduced the number of optimization manoeuvres and reduced the potential for dental trauma when compared to the Macintosh, in both the normal and simulated difficult intubation scenarios. In contrast, the Truview^®increased the duration of intubation attempts, and required a greater number of optimization manoeuvres, compared to both the Macintosh and Airtraq^®devices.</p> <p>Conclusion</p> <p>The Airtraq^®laryngoscope performed more favourably than the Macintosh and Truview^®devices when used by Paramedics in this manikin study. Further studies are required to extend these findings to the clinical setting.</p

Chitosan–Starch–Keratin composites: Improving thermo-mechanical and degradation properties through chemical modification

The lysozyme test shows an improved in the degradability rate, the weight loss of the films at 21 days is reduced from 73 % for chitosan-starch matrix up to 16 % for the composites with 5wt% of quill; but all films show a biodegradable character depending on keratin type and chemical modification. The outstanding properties related to the addition of treated keratin materials show that these natural composites are a remarkable alternative to potentiat-ing chitosan–starch films with sustainable featuresChitosan–starch polymers are reinforced with different keratin materials obtained from chicken feather. Keratin materials are treated with sodium hydroxide; the modified surfaces are rougher in comparison with untreated surfaces, observed by Scanning Electron Microscopy. The results obtained by Differential Scanning Calorimetry show an increase in the endothermic peak related to water evaporation of the films from 92 °C (matrix) up to 102–114 °C (reinforced composites). Glass transition temperature increases from 126 °C in the polymer matrix up to 170–200 °C for the composites. Additionally, the storage modulus in the composites is enhanced up to 1614 % for the composites with modified ground quill, 2522 % for composites with modified long fiber and 3206 % for the composites with modified short fiber. The lysozyme test shows an improved in the degradability rate, the weight loss of the films at 21 days is reduced from 73 % for chitosan-starch matrix up to 16 % for the composites with 5wt% of quill; but all films show a biodegradable character depending on keratin type and chemical modification. The outstanding properties related to the addition of treated keratin materials show that these natural composites are a remarkable alternative to potentiat-ing chitosan–starch films with sustainable featuresUniversidad Autónoma del Estado de México Tecnológico Nacional de México, Instituto Tecnológico de Querétaro Universidad Nacional Autónoma de México Tecnológico Nacional de México, Instituto Tecnológico de Celaya Universidad Autónoma de Cd. Juáre

Facilitating Next-Generation Pre-Exposure Prophylaxis Clinical Trials Using HIV Recent Infection Assays: A Consensus Statement from the Forum HIV Prevention Trial Design Project

Standard-of-care HIV pre-exposure prophylaxis (PrEP) is highly efficacious, but uptake of and persistence on a daily oral pill is low in many settings. Evaluation of alternate PrEP products will require innovation to avoid the unpractically large sample sizes in noninferiority trials. We propose estimating HIV incidence in people not on PrEP as an external counterfactual to which on-PrEP incidence in trial subjects can be compared. HIV recent infection testing algorithms (RITAs), such as the limiting antigen avidity assay plus viral load used on specimens from untreated HIV positive people identified during screening, is one possible approach. Its feasibility is partly dependent on the sample size needed to ensure adequate power, which is impacted by RITA performance, the number of recent infections identified, the expected efficacy of the intervention, and other factors. Screening sample sizes to support detection of an 80% reduction in incidence for 3 key populations are more modest, and comparable to the number of participants in recent phase III PrEP trials. Sample sizes would be significantly larger in populations with lower incidence, where the false recency rate is higher or if PrEP efficacy is expected to be lower. Our proposed counterfactual approach appears to be feasible, offers high statistical power, and is nearly contemporaneous with the on-PrEP population. It will be important to monitor the performance of this approach during new product development for HIV prevention. If successful, it could be a model for preventive HIV vaccines and prevention of other infectious diseases

CUORE and CUORE-0 experiments

Neutrino oscillation experiments proved that neutrinos have mass and this enhanced the interest in neutrinoless double-beta decay (0vßß). The observation of this very rare hypothetical decay would prove the leptonic number violation and would give us indications about neutrinos mass hierarchy and absolute mass scale. CUORE (Cryogenic Underground Observatory for Rare Events) is an array of 988 crystals of TeO2, for a total sensitive mass of 741 kg. Its goal is the observation of 0vßß of 130Te. The crystals, placed into the a dilution cryostat, are operated as bolometers at a temperature close to 10 mK. CUORE commissioning phase has been concluded recently in Gran Sasso National Laboratory, Italy, and data taking is expected to start in spring 2017. If target background rate is reached (0.01counts/day/keV/kg), the sensibility of CUORE will be, in five years of data taking, T1/21026years (1? CL). In order to test the quality of materials and optimize the construction procedures, the collaboration realized CUORE-0, that took data from spring of 2013 to summer 2015. Here, after a brief description of CUORE, I report its commissioning status and CUORE-0 results

Lowering the CUORE energy threshold

The Cryogenic Underground Observatory for Rare Events (CUORE) is a ton-scale double beta decay experiment based on TeO2 cryogenic bolometers and is currently in the last construction stage at the Gran Sasso National Laboratory (LNGS). Its primary goal is to observe neutrino-less double beta decay of 130Te, however thanks to the ultra-low background and large projected exposure it could also be suitable for other rare event searches, as the detection of solar axions, neutrinos from type II supernovae or direct detection of dark matter. The sensitivity for these searches will depend on the performance achieved at the low energy threshold. For this reason a trigger algorithm based on continuous data filtering has been developed which will allow lowering the threshold down to the few keV region. The new trigger has been tested in CUORE-0, a single-tower CUORE prototype consisting of 52 TeO2 bolometers and recently concluded, and here we present the results in terms of trigger efficiency, data selection and low-energy calibration

Status and prospects for CUORE

CUORE is a cryogenic detector consisting of 988 TeO2 crystals, 750 g each, and will be operated at a temperature of ~10 mK, to search for neutrinoless double beta decay (0¿ßß) of 130Te. The detector, in the final stages of construction at the Laboratori Nazionali del Gran Sasso (Italy), will start its operations in 2016. CUORE-0, its pilot experiment, has proven the feasibility of CUORE, demonstrating that the target background of 0.01 counts/keV/kg/y and the energy resolution of 5 keV are within reach. CUORE-0 also made the most precise measurement of the 2¿ßß decay. The expected sensitivity of CUORE to the 0¿ßß 130Te half-life is 9 •1025y, for 5 years of data taking. Here, we report the most recent results of CUORE-0, their implications for CUORE, and the current status of the CUORE experiment