292 research outputs found
Age- and stress-associated C. elegans granulins impair lysosomal function and induce a compensatory HLH-30/TFEB transcriptional response.
The progressive failure of protein homeostasis is a hallmark of aging and a common feature in neurodegenerative disease. As the enzymes executing the final stages of autophagy, lysosomal proteases are key contributors to the maintenance of protein homeostasis with age. We previously reported that expression of granulin peptides, the cleavage products of the neurodegenerative disease protein progranulin, enhance the accumulation and toxicity of TAR DNA binding protein 43 (TDP-43) in Caenorhabditis elegans (C. elegans). In this study we show that C. elegans granulins are produced in an age- and stress-dependent manner. Granulins localize to the endolysosomal compartment where they impair lysosomal protease expression and activity. Consequently, protein homeostasis is disrupted, promoting the nuclear translocation of the lysosomal transcription factor HLH-30/TFEB, and prompting cells to activate a compensatory transcriptional program. The three C. elegans granulin peptides exhibited distinct but overlapping functional effects in our assays, which may be due to amino acid composition that results in distinct electrostatic and hydrophobicity profiles. Our results support a model in which granulin production modulates a critical transition between the normal, physiological regulation of protease activity and the impairment of lysosomal function that can occur with age and disease
Determining Optimum Soil Type and Salinity for Rearing the Federally Endangered Salt Creek Tiger Beetle, \u3ci\u3eCicindela (Ellipsoptera) nevadica lincolniana\u3c/i\u3e Casey (Coleoptera: Carabidae: Cicindelinae)
Effective rearing methods are needed to recover the federally endangered Salt Creek tiger beetle, Cicindela (Ellipsoptera) nevadica lincolniana Casey, a subspecies that occurs exclusively in saline wetlands and seeps along Little Salt Creek in Lancaster County, Nebraska. Experiments were initiated to determine soil type and salinity concentrations appropriate for stimulating female oviposition in laboratory settings to produce larvae and/or adults for reintroduction to native habitats. In 2013, there were highly significant differences between native soil and a sand/loess soil mixture, but no differences between two salinity levels, 0.354 M and 0.5 M. In 2014, using only a sand/loess soil mixture, there were again no differences between the test salinity levels. A sand/loess soil mixture of either 0.354M or 0.5M salinity was determined to be optimum for egg production
Determining Optimum Soil Type and Salinity for Rearing the Federally Endangered Salt Creek Tiger Beetle, \u3ci\u3eCicindela (Ellipsoptera) nevadica lincolniana\u3c/i\u3e Casey (Coleoptera: Carabidae: Cicindelinae)
Effective rearing methods are needed to recover the federally endangered Salt Creek tiger beetle, Cicindela (Ellipsoptera) nevadica lincolniana Casey, a subspecies that occurs exclusively in saline wetlands and seeps along Little Salt Creek in Lancaster County, Nebraska. Experiments were initiated to determine soil type and salinity concentrations appropriate for stimulating female oviposition in laboratory settings to produce larvae and/or adults for reintroduction to native habitats. In 2013, there were highly significant differences between native soil and a sand/loess soil mixture, but no differences between two salinity levels, 0.354 M and 0.5 M. In 2014, using only a sand/loess soil mixture, there were again no differences between the test salinity levels. A sand/loess soil mixture of either 0.354M or 0.5M salinity was determined to be optimum for egg production
Quadrimodal Distribution of Death after Trauma: Predictors of Death in the Fourth Peak
Introduction: Patterns of death after trauma are changing due to diagnostic and treatment advances. We examined mortality in critically injured patients at risk of death after discharge.
Methods: We reviewed all critically injured (Injury Severity Scoreâ„25 AND death in Emergency Room , death within 24hrs, OR ICU admission\u3e24hrs) adults (ageâ„18) admitted to a Level 1 trauma center (01/01/2000-12/31/2010) and determined death post-discharge (Social Security Death Index) of patients discharged alive. We compared demographics, injury data, and critical care resource utilization between those who died during follow-up and survivors using univariate tests and Cox proportional hazards models.
Results: Of 1,695 critically injured patients, 1135 (67%) were discharged alive. As of 05/1/2012, 977 (58%) index survivors were alive (median follow-up 62mos (IQR35,96)). Of 158 deaths post-discharge, 75 (47%) occurred within the first year. Patients who died post-discharge had longer hospital (24dys (IQR13,38) vs. 17dys (IQR10,27)) and ICU LOS (17dys (IQR6,29) vs. 8dys (IQR4,19)) and were more likely to undergo tracheostomies (36.1% vs. 15.6%, p16dys increased risk of death at one year (HR1.94 (1.22,3.06)) and by the end of follow-up (HR2.19 (1.58,3.04)) compared to shorter ICU stays.
Conclusion: We propose the first year after discharge as the fourth peak of trauma related mortality. Duration of ICU LOS during index hospitalization is associated with post-discharge mortality
Analysis of remarkable bolides observed between June and July 2022 in the framework of the Southwestern EuropeMeteor Network
Some of the bright bolides spotted in the framework of the Southwestern Europe Meteor Network from June to July
2022 are discussed here. These were observed from Spain. Their absolute magnitude ranges from â6 to â11. Fireballs
included in this work were generated by different sources: the sporadic background, major meteoroid streams, and
poorly known streams.Spanish Ministry of
Science and Innovation (project PID2019-105797GB-I00). State
Agency for Research of the Spanish MCIU through the
âCenter of Excellence Severo Ochoaâ award to the Instituto
de AstrofĂsica de AndalucĂa (SEV-2017-0709). Spanish grant AYA
- RTI2018 â 098657 â J - I00 âLEO-SBNAFâ (MCIU / AEI
/ FEDER, UE)
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I owe you: age-related similarities and differences in associative memory for gains and losses
Older adults often experience associative memory impairments but can sometimes remember important information. The current experiments investigate potential age-related similarities and differences associate memory for gains and losses. Younger and older participants were presented with faces and associated dollar amounts, which indicated how much money the person âowedâ the participant, and were later given a cued recall test for the dollar amount. Experiment 1 examined face-dollar amount pairs while Experiment 2 included negative dollar amounts to examine both gains and losses. While younger adults recalled more information relative to older adults, both groups were more accurate in recalling the correct value associated with high value faces compared to lower value faces and remembered gist-information about the values. However, negative values (losses) did not have a strong impact on recall among older adults versus younger adults, illustrating important associative memory differences between younger and older adults
Estimation of the national disease burden of influenza-associated severe acute respiratory illness in Kenya and Guatemala : a novel methodology
Background:
Knowing the national disease burden of severe influenza in low-income countries can inform policy decisions around influenza treatment and prevention. We present a novel methodology using locally generated data for estimating this burden.
Methods and Findings:
This method begins with calculating the hospitalized severe acute respiratory illness (SARI) incidence for children <5 years old and persons â„5 years old from population-based surveillance in one province. This base rate of SARI is then adjusted for each province based on the prevalence of risk factors and healthcare-seeking behavior. The percentage of SARI with influenza virus detected is determined from provincial-level sentinel surveillance and applied to the adjusted provincial rates of hospitalized SARI. Healthcare-seeking data from healthcare utilization surveys is used to estimate non-hospitalized influenza-associated SARI. Rates of hospitalized and non-hospitalized influenza-associated SARI are applied to census data to calculate the national number of cases. The method was field-tested in Kenya, and validated in Guatemala, using data from August 2009âJuly 2011. In Kenya (2009 population 38.6 million persons), the annual number of hospitalized influenza-associated SARI cases ranged from 17,129â27,659 for children <5 years old (2.9â4.7 per 1,000 persons) and 6,882â7,836 for persons â„5 years old (0.21â0.24 per 1,000 persons), depending on year and base rate used. In Guatemala (2011 population 14.7 million persons), the annual number of hospitalized cases of influenza-associated pneumonia ranged from 1,065â2,259 (0.5â1.0 per 1,000 persons) among children <5 years old and 779â2,252 cases (0.1â0.2 per 1,000 persons) for persons â„5 years old, depending on year and base rate used. In both countries, the number of non-hospitalized influenza-associated cases was several-fold higher than the hospitalized cases.
Conclusions: Influenza virus was associated with a substantial amount of severe disease in Kenya and Guatemala. This
method can be performed in most low and lower-middle income countries
The First Quiescent Galaxies in TNG300
We identify the first quiescent galaxies in TNG300, the largest volume of the
IllustrisTNG cosmological simulation suite, and explore their quenching
processes and time evolution to z=0. We find that the first quiescent galaxies
with stellar masses M_* > 3 x 10^{10} M_sun and specific star formation rates
sSFR < 10^{-11} yr^{-1} emerge at z~4.2 in TNG300. Suppression of star
formation in these galaxies begins with a thermal mode of AGN feedback at z~6,
and a kinetic feedback mode acts in each galaxy by z~4.7 to complete the
quenching process, which occurs on a time-scale of ~0.35 Gyr. Surprisingly, we
find that the majority of these galaxies are not the main progenitors of their
z=0 descendants; instead, four of the five galaxies fall into more massive
galaxies in subsequent mergers at a range of redshifts 2.5 < z < 0.2. By z=0,
these descendants are the centres of galaxy clusters with average stellar
masses of 8 x 10^{11} M_sun. We make predictions for the first quenched
galaxies to be located by the James Webb Space Telescope (JWST).Comment: 6 pages, 4 figure
Analysis of bright bolides recorded between October and November 2022 by the Southwestern Europe Meteor Network
We present in this work the analysis of some of the bright fireballs spotted in the framework of the Southwestern
Europe Meteor Network (SWEMN) between October and November 2022. They have been observed from the
Iberian Peninsula and had a maximum brightness ranging from mag. â7 to mag. â15. Most meteors included in this
report were linked to the sporadic background and also to the Southern Taurids.Spanish Ministry of Science and Innovation (project PID2019-105797GB-I00). State Agency for Research of the Spanish MCIU through the âCenter of Excellence Severo Ochoaâ award to the Instituto de AstrofĂsica de AndalucĂa (SEV-2017-0709). Spanish grant AYA -RTI2018â098657âJ-I00 âLEO-SBNAFâ (MCIU / AEI / FEDER, UE)
Remarkable fireballs spotted in the framework of the Southwestern Europe Meteor Network along August and September 2022
Some of the bright bolides observed in the framework of the Southwestern Europe Meteor Network between August
and September 2022 are described in this work. These have been spotted from the Iberian Peninsula. Their maximum
luminosity ranges from mag. â7 to mag. â12. One of these bolides gave rise to a meteorite.Spanish Ministry of Science and Innovation (project PID2019-105797GB-I00). Spanish MCIU through the
âCenter of Excellence Severo Ochoaâ award to the Instituto
de AstrofĂsica de AndalucĂa (SEV-2017-0709).Spanish grant AYA
- RTI2018 â 098657 -J- I00 âLEO-SBNAFâ (MCIU / AEI
/ FEDER, UE)
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