473 research outputs found
Unifying moralityâs influence on non-moral judgments: The relevance of alternative possibilities
Past work has demonstrated that peopleâs moral judgments can influence their judgments in a number of domains that might seem to involve straightforward matters of fact, including judgments about freedom, causation, the doing/allowing distinction, and intentional action. The present studies explore whether the effect of morality in these four domains can be explained by changes in the relevance of alternative possibilities. More precisely, we propose that moral judgment influences the degree to which people regard certain alternative possibilities as relevant, which in turn impacts intuitions about freedom, causation, doing/allowing, and intentional action. Employing the stimuli used in previous research, Studies 1a, 2a, 3a, and 4a show that the relevance of alternatives is influenced by moral judgments and mediates the impact of morality on non-moral judgments. Studies 1b, 2b, 3b, and 4b then provide direct empirical evidence for the link between the relevance of alternatives and judgments in these four domains by manipulating (rather than measuring) the relevance of alternative possibilities. Lastly, Study 5 demonstrates that the critical mechanism is not whether alternative possibilities are considered, but whether they are regarded as relevant. These studies support a unified framework for understanding the impact of morality across these very different kinds of judgments
Neglecting plantâmicrobe symbioses leads to underestimation of modeled climate impacts
The extent to which terrestrial ecosystems slow climate change by sequestering carbon hinges in part on nutrient limitation. We used a coupled carbonâclimate model that accounts for the carbon cost to plants of supporting nitrogen-acquiring microbial symbionts to explore how nitrogen limitation affects global climate. To do this, we first calculated the reduction in net primary production due to the carbon cost of nitrogen acquisition. We then used a climate model to estimate the impacts of the resulting increase in atmospheric CO2 on temperature and precipitation regimes. The carbon costs of supporting symbiotic nitrogen uptake reduced net primary production by 8.1âPgâCâyrâ1, with the largest absolute effects occurring in tropical forest biomes and the largest relative changes occurring in boreal and alpine biomes. Globally, our model predicted relatively small changes in climate due to the carbon cost of nitrogen acquisition with temperature increasing by 0.1ââC and precipitation decreasing by 6âmmâyrâ1. However, there were strong regional impacts, with the largest impact occurring in boreal and alpine ecosystems, where such costs were estimated to increase temperature by 1.0ââC and precipitation by 9âmmâyrâ1. As such, our results suggest that carbon expenditures to support nitrogen-acquiring microbial symbionts have critical consequences for Earth\u27s climate, and that carbonâclimate models that omit these processes will overpredict the land carbon sink and underpredict climate change
Toxoplasma gondii AP2IX-4 Regulates Gene Expression during Bradyzoite Development
Toxoplasma gondii is a protozoan parasite of great importance to human and animal health. In the host, this obligate intracellular parasite persists as a tissue cyst that is imperceptible to the immune response and unaffected by current therapies. The tissue cysts facilitate transmission through predation and give rise to chronic cycles of toxoplasmosis in immunocompromised patients. Transcriptional changes accompany conversion of the rapidly replicating tachyzoites into the encysted bradyzoites, and yet the mechanisms underlying these alterations in gene expression are not well defined. Here we show that AP2IX-4 is a nuclear protein exclusively expressed in tachyzoites and bradyzoites undergoing division. Knockout of AP2IX-4 had no discernible effect on tachyzoite replication but resulted in a reduced frequency of tissue cyst formation following alkaline stress induction-a defect that is reversible by complementation. AP2IX-4 has a complex role in regulating bradyzoite gene expression, as the levels of many bradyzoite mRNAs dramatically increased beyond those seen under conditions of normal stress induction in AP2IX-4 knockout parasites exposed to alkaline media. The loss of AP2IX-4 also resulted in a modest virulence defect and reduced cyst burden in chronically infected mice, which was reversed by complementation. These findings illustrate that the transcriptional mechanisms responsible for tissue cyst development operate across the intermediate life cycle from the dividing tachyzoite to the dormant bradyzoite. IMPORTANCEToxoplasma gondii is a single-celled parasite that persists in its host as a transmissible tissue cyst. How the parasite converts from its replicative form to the bradyzoites housed in tissue cysts is not well understood, but the process clearly involves changes in gene expression. Here we report that parasites lacking a cell cycle-regulated transcription factor called AP2IX-4 display reduced frequencies of tissue cyst formation in culture and in a mouse model of infection. Parasites missing AP2IX-4 lose the ability to regulate bradyzoite genes during tissue cyst development. Expressed in developing bradyzoites still undergoing division, AP2IX-4 may serve as a useful marker in the study of transitional forms of the parasite
Engineered neural tissue made using hydrogels derived from decellularised tissues for the regeneration of peripheral nerves
Engineered neural tissue (EngNT) promotes in vivo axonal regeneration. Decellularised materials (dECM) are complex biologic scaffolds that can improve the cellular environment and also encourage positive tissue remodelling in vivo. We hypothesised that we could incorporate a hydrogel derived from a decellularised tissue (dECMh) into EngNT, thereby providing an alternative to the currently used purified collagen I hydrogel for the first time. Decellularisation was carried out on bone (B-ECM), liver (LIV-ECM), and small intestinal (SIS-ECM) tissues and the resultant dECM was biochemically and mechanically characterised. dECMh differed in mechanical and biochemical properties that likely had an effect on Schwann cell behaviour observed in metabolic activity and contraction profiles. Cellular alignment was observed in tethered moulds within the B-ECM and SIS-ECM derived hydrogels only. No difference was observed in dorsal root ganglia (DRG) neurite extension between the dECMh groups and collagen I groups when applied as a coverslip coating, however, when DRG were seeded atop EngNT constructs, only the B-ECM derived EngNT performed similarly to collagen I derived EngNT. B-ECM EngNT further exhibited similar axonal regeneration to collagen I EngNT in a 10 mm gap rat sciatic nerve injury model after 4 weeks. Our results have shown that various dECMh can be utilised to produce EngNT that can promote neurite extension in vitro and axonal regeneration in vivo
Zoledronate treatment duration is linked to bisphosphonateârelated osteonecrosis of the jaw prevalence in rice rats with generalized periodontitis
ObjectivesTo determine the extent that zoledronate (ZOL) dose and duration is associated with bisphosphonateârelated osteonecrosis of the jaw (BRONJ) prevalence in rice rats with generalized periodontitis (PD), characterize structural and tissueâlevel features of BRONJâlike lesions in this model, and examine the specific antiâresorptive role of ZOL in BRONJ.Materials and MethodsRice rats (n = 228) consumed high sucroseâcasein diet to enhance generalized PD. Groups of rats received 0, 8, 20, 50 or 125 ”g/kg IV ZOL/4 weeks encompassing osteoporosis and oncology ZOL doses. Rats from each dose group (n = 9â16) were necropsied after 12, 18, 24 and 30 weeks of treatment. BRONJâlike lesion prevalence and tissueâlevel features were assessed grossly, histopathologically and by MicroCT. ZOL bone turnover effects were assessed by femoral peripheral quantitative computed tomography, serum bone turnover marker ELISAs and osteoclast immunolabelling.ResultsPrevalence of BRONJâlike lesions was significantly associated with (a) ZOL treatment duration, but plateaued at the lowest oncologic dose, and (b) there was a similar doseârelated plateau in the systemic antiâresorptive effect of ZOL. ZOL and BRONJâlike lesions also altered the structural and tissueâlevel features of the jaw.ConclusionThe relationship between BRONJâlike lesion prevalence and ZOL dose and duration varies depending on the coâ or preâexisting oral risk factor. At clinically relevant doses of ZOL, BRONJâlike lesions are associated with antiâresorptive activity.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149302/1/odi13052.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149302/2/odi13052_am.pd
Diverse Roles of Mitochondria in Immune Responses: Novel Insights Into Immuno-Metabolism
Lack of immune system cells or impairment in differentiation of immune cells is the basis for many chronic diseases. Metabolic changes could be the root cause for this immune cell impairment. These changes could be a result of altered transcription, cytokine production from surrounding cells, and changes in metabolic pathways. Immunity and mitochondria are interlinked with each other. An important feature of mitochondria is it can regulate activation, differentiation, and survival of immune cells. In addition, it can also release signals such as mitochondrial DNA (mtDNA) and mitochondrial ROS (mtROS) to regulate transcription of immune cells. From current literature, we found that mitochondria can regulate immunity in different ways. First, alterations in metabolic pathways (TCA cycle, oxidative phosphorylation, and FAO) and mitochondria induced transcriptional changes can lead to entirely different outcomes in immune cells. For example, M1 macrophages exhibit a broken TCA cycle and have a pro-inflammatory role. By contrast, M2 macrophages undergo ÎČ-oxidation to produce anti-inflammatory responses. In addition, amino acid metabolism, especially arginine, glutamine, serine, glycine, and tryptophan, is critical for T cell differentiation and macrophage polarization. Second, mitochondria can activate the inflammatory response. For instance, mitochondrial antiviral signaling and NLRP3 can be activated by mitochondria. Third, mitochondrial mass and mobility can be influenced by fission and fusion. Fission and fusion can influence immune functions. Finally, mitochondria are placed near the endoplasmic reticulum (ER) in immune cells. Therefore, mitochondria and ER junction signaling can also influence immune cell metabolism. Mitochondrial machinery such as metabolic pathways, amino acid metabolism, antioxidant systems, mitochondrial dynamics, mtDNA, mitophagy, and mtROS are crucial for immune functions. Here, we have demonstrated how mitochondria coordinate to alter immune responses and how changes in mitochondrial machinery contribute to alterations in immune responses. A better understanding of the molecular components of mitochondria is necessary. This can help in the development of safe and effective immune therapy or prevention of chronic diseases. In this review, we have presented an updated prospective of the mitochondrial machinery that drives various immune responses
Diagnostics for COVID-19: A case for field-deployable, rapid molecular tests for community surveillance
Across the globe, the outbreak of the COVID-19 pandemic is causing distress with governments doing everything in their power to contain the spread of the novel coronavirus (SARS-CoV-2) to prevent morbidity and mortality. Actions are being implemented to keep health care systems from being overstretched and to curb the outbreak. Any policy responses aimed at slowing down the spread of the virus and mitigating its immediate effects on health care systems require a firm basis of information about the absolute number of currently infected people, growth rates, and locations/hotspots of infections. The only way to obtain this base of information is by conducting numerous tests in a targeted way. Currently, in Ghana, there is a centralized testing approach, that takes 4-5 days for samples to be shipped and tested at central reference laboratories with results communicated to the district, regional and nationalstakeholders. This delay in diagnosis increases the risk of ongoing transmission in communities and vulnerable institutions. We have validated, evaluated and deployed an innovative diagnostic tool on a mobile laboratory platform to accelerate the COVID-19 testing. A preliminary result of 74 samples from COVID-19 suspected cases has a positivity rate of 12% with a turn-around time of fewer than 3 hours from sample taking to reporting of results, significantly reducing the waiting time from days to hours, enabling expedient response by the health system for contact tracing to reduce transmission and additionally improving case management
On-sky speckle nulling through a single-mode fiber with the Keck Planet Imager and Characterizer
The Keck Planet Imager and Characterizer (KPIC) is an instrument at the Keck
II telescope that enables high-resolution spectroscopy of directly imaged
exoplanets and substellar companions. KPIC uses single-mode fibers to couple
the adaptive optics system to Keck's near-infrared spectrometer (NIRSPEC).
However, KPIC's sensitivity at small separations is limited by the leakage of
stellar light into the fiber. Speckle nulling uses a deformable mirror to
destructively interfere starlight with itself, a technique typically used to
reduce stellar signal on a focal-plane imaging detector. We present the first
on-sky demonstration of speckle nulling through an optical fiber with KPIC,
using NIRSPEC to collect exposures that measure speckle phase for
quasi-real-time wavefront control while also serving as science data. We repeat
iterations of measurement and correction, each using at least 5 exposures. We
show a decrease in the on-sky leaked starlight by a factor of 2.6 to 2.8 in the
targeted spectral order, at a spatial separation of 2.0 {\lambda}/D in K-band.
This corresponds to an estimated factor of 2.6 to 2.8 decrease in the required
exposure time to reach a given SNR, relative to conventional KPIC observations.
The performance of speckle nulling is limited by instability in the speckle
phase: when the loop is opened, the null-depth degrades by a factor of 2 on the
timescale of a single phase measurement, which would limit the suppression that
can be achieved. Future work includes exploring gradient-descent methods, which
may be faster and thereby able to achieve deeper nulls. In the meantime, the
speckle nulling algorithm demonstrated in this work can be used to decrease
stellar leakage and improve the signal-to-noise of science observations.Comment: 18 pages, 4 figure
SN 2009bb: a Peculiar Broad-Lined Type Ic Supernova
Ultraviolet, optical, and near-infrared photometry and optical spectroscopy
of the broad-lined Type Ic supernova (SN) 2009bb are presented, following the
flux evolution from -10 to +285 days past B-band maximum. Thanks to the very
early discovery, it is possible to place tight constraints on the SN explosion
epoch. The expansion velocities measured from near maximum spectra are found to
be only slightly smaller than those measured from spectra of the prototype
broad-lined SN 1998bw associated with GRB 980425. Fitting an analytical model
to the pseudo-bolometric light curve of SN 2009bb suggests that 4.1+-1.9 Msun
of material was ejected with 0.22 +-0.06 Msun of it being 56Ni. The resulting
kinetic energy is 1.8+-0.7x10^52 erg. This, together with an absolute peak
magnitude of MB=-18.36+-0.44, places SN 2009bb on the energetic and luminous
end of the broad-lined Type Ic (SN Ic) sequence. Detection of helium in the
early time optical spectra accompanied with strong radio emission, and high
metallicity of its environment makes SN 2009bb a peculiar object. Similar to
the case for GRBs, we find that the bulk explosion parameters of SN 2009bb
cannot account for the copious energy coupled to relativistic ejecta, and
conclude that another energy reservoir (a central engine) is required to power
the radio emission. Nevertheless, the analysis of the SN 2009bb nebular
spectrum suggests that the failed GRB detection is not imputable to a large
angle between the line-of-sight and the GRB beamed radiation. Therefore, if a
GRB was produced during the SN 2009bb explosion, it was below the threshold of
the current generation of gamma-ray instruments.Comment: Accepted for publication in Ap
The Carnegie Supernova Project: First Near-Infrared Hubble Diagram to z~0.7
The Carnegie Supernova Project (CSP) is designed to measure the luminosity
distance for Type Ia supernovae (SNe Ia) as a function of redshift, and to set
observational constraints on the dark energy contribution to the total energy
content of the Universe. The CSP differs from other projects to date in its
goal of providing an I-band {rest-frame} Hubble diagram. Here we present the
first results from near-infrared (NIR) observations obtained using the Magellan
Baade telescope for SNe Ia with 0.1 < z < 0.7. We combine these results with
those from the low-redshift CSP at z <0.1 (Folatelli et al. 2009). We present
light curves and an I-band Hubble diagram for this first sample of 35 SNe Ia
and we compare these data to 21 new SNe Ia at low redshift. These data support
the conclusion that the expansion of the Universe is accelerating. When
combined with independent results from baryon acoustic oscillations (Eisenstein
et al. 2005), these data yield Omega_m = 0.27 +/- 0.0 (statistical), and
Omega_DE = 0.76 +/- 0.13 (statistical) +/- 0.09 (systematic), for the matter
and dark energy densities, respectively. If we parameterize the data in terms
of an equation of state, w, assume a flat geometry, and combine with baryon
acoustic oscillations, we find that w = -1.05 +/- 0.13 (statistical) +/- 0.09
(systematic). The largest source of systematic uncertainty on w arises from
uncertainties in the photometric calibration, signaling the importance of
securing more accurate photometric calibrations for future supernova cosmology
programs. Finally, we conclude that either the dust affecting the luminosities
of SNe Ia has a different extinction law (R_V = 1.8) than that in the Milky Way
(where R_V = 3.1), or that there is an additional intrinsic color term with
luminosity for SNe Ia independent of the decline rate.Comment: 44 pages, 23 figures, 9 tables; Accepted for publication in the
Astrophysical Journa
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