1,168 research outputs found
Shaped Laser Pulses for Microsecond Time-Resolved Cryo-EM: Outrunning Crystallization During Flash Melting
Water vitrifies if cooled at rates above K/s. Surprisingly,
this process cannot simply be reversed by heating the resulting amorphous ice
at a similar rate. Instead, we have recently shown that the sample transiently
crystallizes even if the heating rate is more than one order of magnitude
higher. This may present an issue for microsecond time-resolved cryo-electron
microscopy experiments, in which vitreous ice samples are briefly flash melted
with a laser pulse, since transient crystallization could potentially alter the
dynamics of the embedded proteins. Here, we demonstrate how shaped microsecond
laser pulses can be used to increase the heating rate and outrun
crystallization during flash melting of amorphous solid water (ASW) samples. We
use time-resolved electron diffraction experiments to determine that the
critical heating rate is about K/s, more than two orders of magnitude
higher than the critical cooling rate. Our experiments add to the toolbox of
the emerging field of microsecond time-resolved cryo-electron microscopy by
demonstrating a straightforward approach for avoiding crystallization during
laser melting and for achieving significantly higher heating rates, which paves
the way for nanosecond time-resolved experiments
Nuclear RNP complex assembly initiates cytoplasmic RNA localization
Cytoplasmic localization of mRNAs is a widespread mechanism for generating cell polarity and can provide the basis for patterning during embryonic development. A prominent example of this is localization of maternal mRNAs in Xenopus oocytes, a process requiring recognition of essential RNA sequences by protein components of the localization machinery. However, it is not yet clear how and when such protein factors associate with localized RNAs to carry out RNA transport. To trace the RNA–protein interactions that mediate RNA localization, we analyzed RNP complexes from the nucleus and cytoplasm. We find that an early step in the localization pathway is recognition of localized RNAs by specific RNA-binding proteins in the nucleus. After transport into the cytoplasm, the RNP complex is remodeled and additional transport factors are recruited. These results suggest that cytoplasmic RNA localization initiates in the nucleus and that binding of specific RNA-binding proteins in the nucleus may act to target RNAs to their appropriate destinations in the cytoplasm
Flash Melting Amorphous Ice
Water can be vitrified if it is cooled at rates exceeding K/s. This
makes it possible to outrun crystallization in so-called no man's land, a range
of deeply supercooled temperatures where water crystallizes rapidly. One would
naively assume that the process can simply be reversed by heating the resulting
amorphous ice at a similar rate. We demonstrate that this is not the case. When
amorphous ice samples are flash melted with a microsecond laser pulse,
time-resolved electron diffraction reveals that the sample transiently
crystallizes despite a heating rate of more than K/s, demonstrating
that the critical heating rate for outrunning crystallization is significantly
higher than the critical cooling rate during vitrification. Moreover, we
observe different crystallization kinetics for amorphous solid water (ASW) and
hyperquenched glassy water (HGW), which suggests that the supercooled liquids
formed during laser heating transiently retain distinct non-equilibrium
structures that are associated with different nucleation rates. These
experiments open up new avenues for elucidating the crystallization mechanism
of water and studying its dynamics in no man's land. They also add important
mechanistic details to the laser melting and revitrification process that is
integral to the emerging field of microsecond time-resolved cryo-electron
microscopy.Comment: arXiv admin note: text overlap with arXiv:2211.0441
Susceptibility locus on chromosome 1q23-25 for a schizophrenia subtype resembling deficit schizophrenia identified by latent class analysis
Context: Identifying susceptibility genes for schizophrenia may be complicated by phenotypic heterogeneity, with some evidence suggesting that phenotypic heterogeneity reflects genetic heterogeneity. Objective: To evaluate the heritability and conduct genetic linkage analyses of empirically derived, clinically homogeneous schizophrenia subtypes. Design: Latent class and linkage analysis. Setting: Taiwanese field research centers. Participants: The latent class analysis included 1236 Han Chinese individuals with DSM-IV schizophrenia. These individuals were members of a large affected-sibling-pair sample of schizophrenia (606 ascertained families), original linkage analyses of which detected a maximum logarithm of odds (LOD) of 1.8 (z = 2.88) on chromosome 10q22.3. Main Outcome Measures: Multipoint exponential LOD scores by latent class assignment and parametric heterogeneity LOD scores. Results: Latent class analyses identified 4 classes, with 2 demonstrating familial aggregation. The first (LC2) described a group with severe negative symptoms, disorganization, and pronounced functional impairment, resembling "deficit schizophrenia." The second (LC3) described a group with minimal functional impairment, mild or absent negative symptoms, and low disorganization. Using the negative/deficit subtype, we detected genome-wide significant linkage to 1q23-25 (LOD = 3.78, empiric genome-wide P = .01). This region was not detected using the DSM-IV schizophrenia diagnosis, but has been strongly implicated in schizophrenia pathogenesis by previous linkage and association studies.Variants in the 1q region may specifically increase risk for a negative/deficit schizophrenia subtype. Alternatively, these results may reflect increased familiality/heritability of the negative class, the presence of multiple 1q schizophrenia risk genes, or a pleiotropic 1q risk locus or loci, with stronger genotype-phenotype correlation with negative/deficit symptoms. Using the second familial latent class, we identified nominally significant linkage to the original 10q peak region. Conclusion: Genetic analyses of heritable, homogeneous phenotypes may improve the power of linkage and association studies of schizophrenia and thus have relevance to the design and analysis of genome-wide association studies
Electron Diffraction of Water in No Man's Land
A generally accepted understanding of the anomalous properties of water will
only emerge if it becomes possible to systematically characterize water in the
deeply supercooled regime, from where the anomalies appear to emanate. This has
largely remained elusive because water crystallizes rapidly between 160 K and
232 K. Here, we present an experimental approach to rapidly prepare deeply
supercooled water at a well-defined temperature and probe it with electron
diffraction before crystallization occurs. We show that as water is cooled from
room temperature to cryogenic temperature, its structure evolves smoothly,
approaching that of amorphous ice just below 200 K. Our experiments narrow down
the range of possible explanations of the origin for the water anomalies and
open up new avenues for studying supercooled water
Dextran Penetration Through Nonkeratinized and Keratinized Epithelia in Monkeys
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142019/1/jper0424.pd
Genetic influences on cost-efficient organization of human cortical functional networks
The human cerebral cortex is a complex network of functionally specialized regions interconnected by axonal fibers, but the organizational principles underlying cortical connectivity remain unknown. Here, we report evidence that one such principle for functional cortical networks involves finding a balance between maximizing communication efficiency and minimizing connection cost, referred to as optimization of network cost-efficiency. We measured spontaneous fluctuations of the blood oxygenation level-dependent signal using functional magnetic resonance imaging in healthy monozygotic (16 pairs) and dizygotic (13 pairs) twins and characterized cost-efficient properties of brain network functional connectivity between 1041 distinct cortical regions. At the global network level, 60% of the interindividual variance in cost-efficiency of cortical functional networks was attributable to additive genetic effects. Regionally, significant genetic effects were observed throughout the cortex in a largely bilateral pattern, including bilateral posterior cingulate and medial prefrontal cortices, dorsolateral prefrontal and superior parietal cortices, and lateral temporal and inferomedial occipital regions. Genetic effects were stronger for cost-efficiency than for other metrics considered, and were more clearly significant in functional networks operating in the 0.09–0.18 Hz frequency interval than at higher or lower frequencies. These findings are consistent with the hypothesis that brain networks evolved to satisfy competitive selection criteria of maximizing efficiency and minimizing cost, and that optimization of network cost-efficiency represents an important principle for the brain's functional organization
The Lantern Vol. 18, No. 1, Fall 1949
• Want, an Old Freedom Unused • Is History Bunk? • How Things Grow • A Real Gone Poem • Hish Proves Himself • Death? Not Yet! • On the Neglect of Victorian Literature • The Tradition Lives On • To the Other Side • Autumn\u27s Panorama • Autumn Treasure • A Walk • Leaves • The Moment • Dawn • Sentiments • Dustinghttps://digitalcommons.ursinus.edu/lantern/1049/thumbnail.jp
The Lantern Vol. 18, No. 1, Fall 1949
• Want, an Old Freedom Unused • Is History Bunk? • How Things Grow • A Real Gone Poem • Hish Proves Himself • Death? Not Yet! • On the Neglect of Victorian Literature • The Tradition Lives On • To the Other Side • Autumn\u27s Panorama • Autumn Treasure • A Walk • Leaves • The Moment • Dawn • Sentiments • Dustinghttps://digitalcommons.ursinus.edu/lantern/1049/thumbnail.jp
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