Objective
This study aims to accurately evaluate the cardiac structure and function of the frail population in elderly patients with normal ejection fraction (EF) using the 3D volume quantification ...and speckle tracking of echocardiography, to explore the correlation between frailty and cardiac structure and function.
Methods
A total of 350 elderly aged 65 and above in-patients, excluding those with congenital heart disease, cardiomyopathy, and severe valvular heart disease, were included in the study. Patients were divided into non-frail, pre-frail, and frail group. Echocardiography techniques including speckle tracking and 3D volume quantification, were used to analyze the cardiac structure and function of the study subjects. Comparative analysis was statistically significant if
P
< 0.05.
Results
The cardiac structure of the frail group was different compared with non-frail patients, the frail group demonstrated increased left ventricular myocardial mass index (LVMI), but decreased stroke volume. Cardiac function was also impaired in the frail group: reservoir strain and conduit strain of left atrium, strain of right ventricular (RV) free wall, strain of RV septum, 3D EF of RV, and global longitudinal strain of LV were significantly decreased. Frailty was significantly and independently associated with LV hypertrophy (OR 1.889; 95% CI 1.240,2.880;
P
= 0.003), LV diastolic dysfunction (OR 1.496; 95% CI 1.016,2.203;
P
= 0.041), left ventricular global longitudinal strain (LVGLS) reduction (OR 1.697; 95% CI 1.192, 2.416;
P
= 0.003), and reduced RV systolic function (OR 2.200; 95% CI 1.017, 4.759;
P
= 0.045).
Conclusion
Frailty is closely associated with several heart structural and functional alterations, which not only manifested as LV hypertrophy and reduced LV systolic function, but also decreased LV diastolic function, RV systolic function, and left atrial systolic function. Frailty is an independent risk factor for LV hypertrophy, LV diastolic dysfunction, LVGLS reduction, and reduced RV systolic function.
Trial registration number
ChiCTR2000033419. Date of registration: May 31, 2020.
Alzheimer's disease is characterized by the accumulation of amyloid beta (Aβ) and the formation of neurofibrillary tangles. Aβ is the main constituent of senile plaques and is largely involved in ...neuronal death and neuroinflammation. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is one of the main transcriptional coactivator and has been related to many fields such as energy metabolism, cardiovascular disease, neurodegenerative disorders, and so on.
Treatment with Aβ1-42 reduced the expression of PGC-1α in both protein and RNA levels of neuroblastoma N2a cells. Aβ1-42 induced a robust activation of cleaved caspase-3 while PGC-1α suppressed this activation and protected N2a cells from Aβ-induced cell death. Overexpression of PGC-1α significantly reduced the level of main proinflammatory cytokines. In addition, PGC-1α inhibited the transportation of NF-κB p65 from cytoplasm to nucleus and IκBα degradation induced by Aβ1-42.
Our results have demonstrated that PGC-1α can protect neuroblastoma cells against Aβ-induced neuronal death and neuroinflammation. Moreover, this neuroprotective effect of PGC-1α is regulated through NF-κB pathway. Taken together, our work provides evidence that PGC-1α could be beneficial in targeting Aβ neurotoxicity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The frequency, duration, and magnitude of heatwaves and droughts are expected to increase in a warming climate, which can have profound impacts on the environment, society, and public health, and ...these may be severely affected specifically by compound droughts and heatwaves (CDHWs). On the basis of daily maximum temperature data and the one-month standardized precipitation evapotranspiration index (SPEI) from 1961 to 2018, the Gan River Basin (GRB) was taken as a case here to construct CDHW identification indicators and quantify the population exposure to CDHWs. We found that ERA5 reanalysis data performed well in overall simulating temperature, precipitation, one-month SPEI, heatwaves, and CDHWs in the GRB from 1961 to 2018. CDHWs during the period from 1997 to 2018 were slightly higher than that in 1961–1997. CDHWs were more likely to occur in the southern parts of the basin due to the relatively high values of drought–heatwave dependence indices. Atmospheric circulation analysis of the 2003 CDHW in the GRB showed a relatively long-lasting anomalous high pressure and anticyclonic circulation system, accompanied by the positive convective inhibition and surface net solar radiation anomalies. These circulating background fields eventually led to the exceptional 2003 CDHW occurrence in the GRB. The population exposure to CDHWs basically increased, especially for the moderate CDHWs in ERA5. The change in total exposure was mainly due to climate change. Compared with the period from 1989 to 1998, the contributions of the population change effect in 2009–2018 gradually increased with the increase in the CDHW magnitude both in the observations and ERA5 reanalysis data.
Elongator is a six subunit protein complex, conserved from yeast to humans. Mutations in the human Elongator homologue, hELP1, are associated with the neurological disease familial dysautonomia. ...However, how Elongator functions in metazoans, and how the human mutations affect neural functions is incompletely understood. Here we show that in Caenorhabditis elegans, ELPC-1 and ELPC-3, components of the Elongator complex, are required for the formation of the 5-carbamoylmethyl and 5-methylcarboxymethyl side chains of wobble uridines in tRNA. The lack of these modifications leads to defects in translation in C. elegans. ELPC-1::GFP and ELPC-3::GFP reporters are strongly expressed in a subset of chemosensory neurons required for salt chemotaxis learning. elpc-1 or elpc-3 gene inactivation causes a defect in this process, associated with a posttranscriptional reduction of neuropeptide and a decreased accumulation of acetylcholine in the synaptic cleft. elpc-1 and elpc-3 mutations are synthetic lethal together with those in tuc-1, which is required for thiolation of tRNAs having the 5'methylcarboxymethyl side chain. elpc-1; tuc-1 and elpc-3; tuc-1 double mutants display developmental defects. Our results suggest that, by its effect on tRNA modification, Elongator promotes both neural function and development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Neuropeptides are ubiquitous modulators of behavior and physiology. They are packaged in specialized secretory organelles called dense core vesicles (DCVs) that are released upon neural stimulation. ...Unlike synaptic vesicles, which can be recycled and refilled close to release sites, DCVs must be replenished by de novo synthesis in the cell body. Here, we dissect DCV cell biology in vivo in a Caenorhabditis elegans sensory neuron whose tonic activity we can control using a natural stimulus. We express fluorescently tagged neuropeptides in the neuron and define parameters that describe their subcellular distribution. We measure these parameters at high and low neural activity in 187 mutants defective in proteins implicated in membrane traffic, neuroendocrine secretion, and neuronal or synaptic activity. Using unsupervised hierarchical clustering methods, we analyze these data and identify 62 groups of genes with similar mutant phenotypes. We explore the function of a subset of these groups. We recapitulate many previous findings, validating our paradigm. We uncover a large battery of proteins involved in recycling DCV membrane proteins, something hitherto poorly explored. We show that the unfolded protein response promotes DCV production, which may contribute to intertissue communication of stress. We also find evidence that different mechanisms of priming and exocytosis may operate at high and low neural activity. Our work provides a defined framework to study DCV biology at different neural activity levels.
Nowadays, extra heavy oil reservoirs in the Orinoco Heavy-Oil-Belt in Venezuela are exploited via cold production process, which present different production performance in well productivity and ...primary recovery factor. The purpose of this study is to investigate the causes for such differences with the aspect of foamy oil mechanism. Two typical oil samples were adopted from a shallow reservoir in western Junìn region and a middepth reservoir in eastern Carabobo region in the Belt, respectively. A depletion test was conducted using 1D sand-pack with a visualized microscopic flow observation installation for each of the oil samples under simulated reservoir conditions. The production performance, the foamy oil behaviour, and the oil and gas morphology were recorded in real time during the tests. The results indicated that the shallow heavy oil reservoir in the Belt presents a weaker foamy oil phenomenon when compared with the middepth one; its foamy oil behaviour lasts a shorter duration with a smaller scope, with bigger bubble size and less bubble density. The difference in foamy oil behaviour for those two types of heavy oil reservoir is caused by the difference in reservoir pressure, solution GOR, asphaltene content, etc. Cold production presents obvious features of three stages under the action of strong foamy oil displacement mechanism for the middepth heavy oil reservoir, which could achieve a more favourable production performance. In the contrary, no such obvious production characteristics for the shallow heavy oil reservoir are observed due to weaker foamy oil behaviour, and its primary recovery factor is 9.38 percent point lower than which of the middle heavy oil reservoirs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
G protein-coupled receptors (GPCRs) mediate responses to various extracellular and intracellular cues. However, the large number of GPCR genes and their substantial functional redundancy make it ...challenging to systematically dissect GPCR functions in vivo. Here, we employ a CRISPR/Cas9-based approach, disrupting 1654 GPCR-encoding genes in 284 strains and mutating 152 neuropeptide-encoding genes in 38 strains in C. elegans. These two mutant libraries enable effective deorphanization of chemoreceptors, and characterization of receptors for neuropeptides in various cellular processes. Mutating a set of closely related GPCRs in a single strain permits the assignment of functions to GPCRs with functional redundancy. Our analyses identify a neuropeptide that interacts with three receptors in hypoxia-evoked locomotory responses, unveil a collection of regulators in pathogen-induced immune responses, and define receptors for the volatile food-related odorants. These results establish our GPCR and neuropeptide mutant libraries as valuable resources for the C. elegans community to expedite studies of GPCR signaling in multiple contexts.
Besides pro-inflammatory roles, the ancient cytokine interleukin-17 (IL-17) modulates neural circuit function. We investigate IL-17 signaling in neurons, and the extent it can alter organismal ...phenotypes. We combine immunoprecipitation and mass spectrometry to biochemically characterize endogenous signaling complexes that function downstream of IL-17 receptors in C. elegans neurons. We identify the paracaspase MALT-1 as a critical output of the pathway. MALT1 mediates signaling from many immune receptors in mammals, but was not previously implicated in IL-17 signaling or nervous system function. C. elegans MALT-1 forms a complex with homologs of Act1 and IRAK and appears to function both as a scaffold and a protease. MALT-1 is expressed broadly in the C. elegans nervous system, and neuronal IL-17-MALT-1 signaling regulates multiple phenotypes, including escape behavior, associative learning, immunity and longevity. Our data suggest MALT1 has an ancient role modulating neural circuit function downstream of IL-17 to remodel physiology and behavior.
Elongator complex is required for formation of the side chains at position 5 of modified nucleosides 5-carbamoylmethyluridine (ncm⁵U₃₄), 5-methoxycarbonylmethyluridine (mcm⁵U₃₄), and ...5-methoxycarbonylmethyl-2-thiouridine (mcm⁵s²U₃₄) at wobble position in tRNA. These modified nucleosides are important for efficient decoding during translation. In a recent publication, Elongator complex was implicated to participate in telomeric gene silencing and DNA damage response by interacting with proliferating cell nuclear antigen (PCNA). Here we show that elevated levels of tRNA(Lys)(s²UUU), tRNA(Gln)(s²UUG), and tRNA(Glu)(s²UUC), which in a wild-type background contain the mcm⁵s²U nucleoside at position 34, suppress the defects in telomeric gene silencing and DNA damage response observed in the Elongator mutants. We also found that the reported differences in telomeric gene silencing and DNA damage response of various elp3 alleles correlated with the levels of modified nucleosides at U₃₄. Defects in telomeric gene silencing and DNA damage response are also observed in strains with the tuc2Δ mutation, which abolish the formation of the 2-thio group of the mcm⁵s²U nucleoside in tRNA(Lys)(mcm⁵s²UUU), tRNA(Gln)(mcm⁵s²UUG), and tRNA(Glu)(mcm⁵s²UUC). These observations show that Elongator complex does not directly participate in telomeric gene silencing and DNA damage response, but rather that modified nucleosides at U₃₄ are important for efficient expression of gene products involved in these processes. Consistent with this notion, we found that expression of Sir4, a silent information regulator required for assembly of silent chromatin at telomeres, was decreased in the elp3Δ mutants.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
1T-type TiS2 has been recognized as a promising environmentally friendly thermoelectric material with a record ZT of around 0.4 so far. We hereby report the high thermoelectric performance of a ...series of TiS2–xAgSnSe2 composites with nano-AgSnSe2 as an ionized impurity for electron scattering. Electrical conductivities (σ) in the composites increased possibly due to intercalation; moreover, they showed an exceptional power law decay of σ ∝ Tm with m much increased in the temperature range of 400–580 K due to a significant contribution of ionized impurity scattering. Correspondingly, Seebeck coefficients (S) experience a much faster growth from ∼450 K to approach and even surpass that in pristine TiS2. The simultaneous enhancement of σ and S enabled a high power factor of ∼1.55 mW m−1 K−1 at 700 K. Besides, the lattice thermal conductivity was effectively reduced due to enhanced phonon scattering and intercalations, almost by half from 1.9 W m−1 K−1 to 1.0 W m−1 K−1 at 700 K. These synergistic effects renewed the record of ZT for TiS2-based thermoelectrics by almost doubling it to ∼0.8 at 700 K in the TiS2–4%AgSnSe2 composite.
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