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Systematic Analysis of Ribophagy in Human Cells Reveals By-stander Flux During Selective Autophagy
Ribosomes are abundant cellular machines1,2 regulated by assembly, supernumerary subunit turnover, and nascent chain quality control mechanisms1â5. Moreover, nitrogen starvation in yeast has been reported to promote selective ribosome delivery to the vacuole in an autophagy conjugation system-dependent manner, a process called âribophagyâ6,7. However, whether ribophagy in mammals is selective or regulated is unclear. Using Ribo-Keima flux reporters, we find that starvation or mTOR inhibition promotes VPS34-dependent ribophagic flux, which unlike yeast, is largely ATG8 conjugation independent and occurs concomitantly with other cytosolic protein autophagic flux reporters8,9. Ribophagic flux was not induced upon inhibition of translational elongation or nascent chain uncoupling, but was induced in a comparatively selective manner upon proteotoxic stress via arsenite10 or chromosome mis-segregation11 dependent upon VPS34 and ATG8 conjugation. Unexpectedly, agents typically used to induce selective autophagy also promoted increased ribosome and cytosolic protein reporter flux, suggesting significant bulk or âby-standerâ autophagy during what is often considered selective autophagy12,13. These results emphasize the importance of monitoring non-specific cargo flux when assessing selective autophagy pathways
Using limb darkening to measure fundamental parameters of stars
Context. Limb darkening is an important tool for understanding stellar
atmospheres, but most observations measuring limb darkening assume various
parameterizations that yield no significant information about the structure of
stellar atmospheres. Aims. We use a specific limb-darkening relation to study
how the best-fit coefficients relate to fundamental stellar parameters from
spherically symmetric model stellar atmospheres. Methods. Using a grid of
spherically symmetric Atlas model atmospheres, we compute limb-darkening
coefficients, and develop a novel method to predict fundamental stellar
parameters. Results. We find our proposed method predicts the mass of stellar
atmosphere models given only the radius and limb-darkening coefficients,
suggesting that microlensing, interferometric, transit and eclipse observations
can constrain stellar masses. Conclusions. This novel method demonstrates that
limb-darkening parameterizations contain important information about the
structure of stellar atmospheres, with the potential to be a valuable tool for
measuring stellar masses.Comment: 8 pages, 6 figures, 2 tables, A&A accepte
Small-cell neuroendocrine carcinoma of the breast
A small-cell carcinoma is one of the histologic subtypes of primary neuroendocrine carcinomas of the breast. A small-cell carcinoma is a rare entity of the breast and exhibits similar morphologic features as neuroendocrine tumors of the gastrointestinal tract and lung. We present the imaging and pathologic findings of a primary small-cell neuroendocrine carcinoma of the breast. This is the first report of a primary small-cell carcinoma arising from the breast in Korea
The effect of rotation on the abundances of the chemical elements of the A-type stars in the Praesepe cluster
We study how chemical abundances of late B-, A- and early F-type stars evolve
with time, and we search for correlations between the abundance of chemical
elements and other stellar parameters, such as effective temperature and Vsini.
We have observed a large number of B-, A- and F-type stars belonging to open
clusters of different ages. In this paper we concentrate on the Praesepe
cluster (log t = 8.85), for which we have obtained high resolution, high
signal-to-noise ratio spectra of sixteen normal A- and F-type stars and one Am
star, using the SOPHIE spectrograph of the Observatoire de Haute-Provence. For
all the observed stars, we have derived fundamental parameters and chemical
abundances. In addition, we discuss another eight Am stars belonging to the
same cluster, for which the abundance analysis had been presented in a previous
paper. We find a strong correlation between peculiarity of Am stars and Vsini.
The abundance of the elements underabundant in Am stars increases with Vsini,
while it decreases for the overabundant elements. Chemical abundances of
various elements appear correlated with the iron abundance.Comment: Accepted for publication on A&
Identification and expression of equine MER-derived miRNAs
MicroRNAs (miRNAs) are single-stranded, small RNAs (21-23 nucleotides) that function in gene silencing and translational inhibition via the RNA interference mechanism. Most miRNAs originate from host genomic regions, such as intergenic regions, introns, exons, and transposable elements (TEs). Here, we focused on the palindromic structure of medium reiteration frequencies (MERs), which are similar to precursor miRNAs. Five MER consensus sequences (MER5A1, MER53, MER81, MER91C, and MER117) were matched with paralogous transcripts predicted to be precursor miRNAs in the horse genome (equCab2) and located in either intergenic regions or introns. The MER5A1, MER53, and MER91C sequences obtained from RepeatMasker were matched with the eca-miR-544b, eca-miR-1302, and eca-miR-652 precursor sequences derived from Ensembl transcript database, respectively. Each precursor form was anticipated to yield two mature forms, and we confirmed miRNA expression in six different tissues (cerebrum, cerebellum, lung, spleen, adrenal gland, and duodenum) of one thoroughbred horse. MER5A1-derived miRNAs generally showed significantly higher expression in the lung than in other tissues. MER91C-derived miRNA-5p also showed significantly higher expression in the duodenum than in other tissues (cerebellum, lung, spleen, and adrenal gland). The MER117-overlapped expressed sequence tag generated polycistronic miRNAs, which showed higher expression in the duodenum than other tissues. These data indicate that horse MER transposons encode miRNAs that are expressed in several tissues and are thought to have biological functions
The next detectors for gravitational wave astronomy
This paper focuses on the next detectors for gravitational wave astronomy
which will be required after the current ground based detectors have completed
their initial observations, and probably achieved the first direct detection of
gravitational waves. The next detectors will need to have greater sensitivity,
while also enabling the world array of detectors to have improved angular
resolution to allow localisation of signal sources. Sect. 1 of this paper
begins by reviewing proposals for the next ground based detectors, and presents
an analysis of the sensitivity of an 8 km armlength detector, which is proposed
as a safe and cost-effective means to attain a 4-fold improvement in
sensitivity. The scientific benefits of creating a pair of such detectors in
China and Australia is emphasised. Sect. 2 of this paper discusses the high
performance suspension systems for test masses that will be an essential
component for future detectors, while sect. 3 discusses solutions to the
problem of Newtonian noise which arise from fluctuations in gravity gradient
forces acting on test masses. Such gravitational perturbations cannot be
shielded, and set limits to low frequency sensitivity unless measured and
suppressed. Sects. 4 and 5 address critical operational technologies that will
be ongoing issues in future detectors. Sect. 4 addresses the design of thermal
compensation systems needed in all high optical power interferometers operating
at room temperature. Parametric instability control is addressed in sect. 5.
Only recently proven to occur in Advanced LIGO, parametric instability
phenomenon brings both risks and opportunities for future detectors. The path
to future enhancements of detectors will come from quantum measurement
technologies. Sect. 6 focuses on the use of optomechanical devices for
obtaining enhanced sensitivity, while sect. 7 reviews a range of quantum
measurement options
In vivo measurement of bending stiffness in fracture healing
BACKGROUND: Measurement of the bending stiffness a healing fracture represents a valid variable in the assessment of fracture healing. However, currently available methods typically have high measurement errors, even for mild pin loosening. Furthermore, these methods cannot provide actual values of bending stiffness, which precludes comparisons among individual fractures. Thus, even today, little information is available with regards to the fracture healing pattern with respect to actual values of bending stiffness. Our goals were, therefore: to develop a measurement device that would allow accurate and sensitive measurement of bending stiffness, even in the presence of mild pin loosening; to describe the course of healing in individual fractures; and help to evaluate whether the individual pattern of bending stiffness can be predicted at an early stage of healing. METHODS: A new measurement device has been developed to precisely measure the bending stiffness of the healing fracture by simulating four-point-bending. The system was calibrated on aluminum models and intact tibiae. The influence of pin loosening on measurement error was evaluated. The system was tested at weekly intervals in an animal experiment to determine the actual bending stiffness of the fracture. Transverse fractures were created in the right tibia of twelve sheep, and then stabilized with an external fixator. At ten weeks, bending stiffness of the tibiae were determined in a four-point-bending test device to validate the in-vivo-measurement data. RESULTS: In-vivo bending stiffness can be measured accurately and sensitive, even in the early phase of callus healing. Up to a bending stiffness of 10 Nm/degree, measurement error was below 3.4% for one pin loose, and below 29.3% for four pins loose, respectively. Measurement of stiffness data over time revealed a significant logarithmic increase between the third and seventh weeks, whereby the logarithmic rate of change among sheep was similar, but started from different levels. Comparative measurements showed that early individual changes between the third and fourth weeks can be used as a predictor of bending stiffness at seven weeks (r = 0.928) and at ten weeks (r = 0.710). CONCLUSION: Bending stiffness can be measured precisely, with less error in the case of pin loosening. Prediction of the future healing course of the individual fracture can be assessed by changes from the third to the fourth week, with differences in stiffness levels. Therefore, the initial status of the fracture seems to have a high impact on the individual healing course
Investigation of the synthesis, activation, and isosteric heats of COâ adsorption of the isostructural series of metal-organic frameworks Mâ(BTC)â (M = Cr, Fe, Ni, Cu, Mo, Ru)
The synthesis, activation, and heats of COâ adsorption for the known members of the Mâ(BTC)â (HKUST-1) isostructural series (M = Cr, Fe, Ni, Zn, Ni, Cu, Mo) were investigated to gain insight into the impact of COââmetal interactions for COâ storage/separation applications. With the use of modified syntheses and activation procedures, improved BET surface areas were obtained for M = Ni, Mo, and Ru. The zero-coverage isosteric heats of COâ adsorption were measured for the Cu, Cr, Ni, Mo, and Ru analogues and gave values consistent with those reported for MOFs containing coordinatively unsaturated metal sites, but lower than for amine functionalized materials. Notably, the Ni and Ru congeners exhibited the highest COâ affinities in the studied series. These behaviors were attributed to the presence of residual guest molecules in the case of Niâ(BTC)â(MeâNH)â(HâO) and the increased charge of the dimetal secondary building unit in [Ruâ(BTC)â][BTC].Massachusetts Institute of Technology. Energy Initiative (Seed Fund
The DeepMIP contribution to PMIP4: methodologies for selection, compilation and analysis of latest Paleocene and early Eocene climate proxy data, incorporating version 0.1 of the DeepMIP database
This is the final version of the article. Available from European Geosciences Union via the DOI in this record.Data availability.
The data referenced in this manuscript are provided as Supplement Data Files 1 to 8. In the final version, these files will form DeepMIP database version 0.1 and will be accessible online via a citable DOI reference.The early Eocene (56 to 48 million years ago) is inferred to have been the most recent time that Earth's atmospheric CO2 concentrations exceeded 1000âppm. Global mean temperatures were also substantially warmer than those of the present day. As such, the study of early Eocene climate provides insight into how a super-warm Earth system behaves and offers an opportunity to evaluate climate models under conditions of high greenhouse gas forcing. The Deep Time Model Intercomparison Project (DeepMIP) is a systematic modelâmodel and modelâdata intercomparison of three early Paleogene time slices: latest Paleocene, PaleoceneâEocene thermal maximum (PETM) and early Eocene climatic optimum (EECO). A previous article outlined the model experimental design for climate model simulations. In this article, we outline the methodologies to be used for the compilation and analysis of climate proxy data, primarily proxies for temperature and CO2. This paper establishes the protocols for a concerted and coordinated effort to compile the climate proxy records across a wide geographic range. The resulting climate âatlasâ will be used to constrain and evaluate climate models for the three selected time intervals and provide insights into the mechanisms that control these warm climate states. We provide version 0.1 of this database, in anticipation that this will be expanded in subsequent publications.Natural Environment Research Council (NERC)GNS Science Global Change through Time ProgrammeNational Science Foundation (NSF)KU Leuve
Plant-Symbiotic Fungi as Chemical Engineers: Multi-Genome Analysis of the Clavicipitaceae Reveals Dynamics of Alkaloid Loci
The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids. The family includes grass symbionts in the epichloae clade (EpichloĂŤ and Neotyphodium species), which are extraordinarily diverse both in their host interactions and in their alkaloid profiles. Epichloae produce alkaloids of four distinct classes, all of which deter insects, and someâincluding the infamous ergot alkaloidsâhave potent effects on mammals. The exceptional chemotypic diversity of the epichloae may relate to their broad range of host interactions, whereby some are pathogenic and contagious, others are mutualistic and vertically transmitted (seed-borne), and still others vary in pathogenic or mutualistic behavior. We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids. Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci. The organization and dynamics of alkaloid loci and abundant repeat blocks in the epichloae suggested that these fungi are under selection for alkaloid diversification. We suggest that such selection is related to the variable life histories of the epichloae, their protective roles as symbionts, and their associations with the highly speciose and ecologically diverse cool-season grasses
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