We study precursors of failure in hierarchical random fuse network models which can be considered as idealizations of hierarchical (bio)materials where fibrous assemblies are held together by ...multi-level (hierarchical) cross-links. When such structures are loaded towards failure, the patterns of precursory avalanche activity exhibit generic scale invariance: irrespective of load, precursor activity is characterized by power-law avalanche size distributions without apparent cut-off, with power-law exponents that decrease continuously with increasing load. This failure behavior and the ensuing super-rough crack morphology differ significantly from the findings in non-hierarchical structures.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Despite its historic role in evolving our understanding of modern molecular genetics, the mechanism governing the bacteriophage T4
rII
exclusion (Rex) phenotype has remained a mystery for over six ...decades. The Rex system is thought...
The T4r
II
exclusion (Rex) phenotype is the inability of T4
rII
mutant bacteriophage to propagate in hosts (
Escherichia coli
) lysogenized by bacteriophage lambda (λ). The Rex phenotype, triggered by T4
rII
infection of a
rex
+
λ lysogen, results in rapid membrane depolarization imposing a harsh cellular environment that resembles stationary phase. Rex “activation” has been proposed as an altruistic cell death system to protect the λ prophage and its host from T4r
II
superinfection. Although well studied for over 60 years, the mechanism behind Rex still remains unclear. We have identified key nonessential genes involved in this enigmatic exclusion system by examining T4r
II
infection across a collection of
rex
+
single-gene knockouts. We further developed a system for rapid, one-step isolation of host mutations that could attenuate/abrogate the Rex phenotype. For the first time, we identified host mutations that influence Rex activity and
rex
+
host sensitivity to T4
rII
infection. Among others, notable genes include
tolA
,
ompA
,
ompF
,
ompW
,
ompX
,
ompT
,
lpp
,
mglC
, and
rpoS
. They are critical players in cellular osmotic balance and are part of the stationary phase and/or membrane distress regulons. Based on these findings, we propose a new model that connects Rex to the σ
S
, σ
E
regulons and key membrane proteins.
The population frequency of polymorphic alleles varies in time. This variation has a stochastic component, mainly determined by the size of the considered population,
N
e
: genetic drift...
Genetic ...drift is an important evolutionary force of strength inversely proportional to
N
e
, the effective population size. The impact of drift on genome diversity and evolution is known to vary among species, but quantifying this effect is a difficult task. Here we assess the magnitude of variation in drift power among species of animals via its effect on the mutation load – which implies also inferring the distribution of fitness effects of deleterious mutations. To this aim, we analyze the nonsynonymous (amino-acid changing) and synonymous (amino-acid conservative) allele frequency spectra in a large sample of metazoan species, with a focus on the primates
vs.
fruit flies contrast. We show that a Gamma model of the distribution of fitness effects is not suitable due to strong differences in estimated shape parameters among taxa, while adding a class of lethal mutations essentially solves the problem. Using the Gamma + lethal model and assuming that the mean deleterious effects of nonsynonymous mutations is shared among species, we estimate that the power of drift varies by a factor of at least 500 between large-
N
e
and small-
N
e
species of animals,
i.e.
, an order of magnitude more than the among-species variation in genetic diversity. Our results are relevant to Lewontin’s paradox while further questioning the meaning of the
N
e
parameter in population genomics.
Mistranslation, incorporating an amino acid not specified by the “standard” genetic code, has applications in research and synthetic biology. Since mistranslation is toxic, its level must be ...modulated. Using a serine tRNA with a proline anticodon, we identify...
Transfer RNAs (tRNAs) read the genetic code, translating nucleic acid sequence into protein. For tRNA
Ser
the anticodon does not specify its aminoacylation. For this reason, mutations in the tRNA
Ser
anticodon can result in amino acid substitutions, a process called mistranslation. Previously, we found that tRNA
Ser
with a proline anticodon was lethal to cells. However, by incorporating secondary mutations into the tRNA, mistranslation was dampened to a nonlethal level. The goal of this work was to identify second-site substitutions in tRNA
Ser
that modulate mistranslation to different levels. Targeted changes to putative identity elements led to total loss of tRNA function or significantly impaired cell growth. However, through genetic selection, we identified 22 substitutions that allow nontoxic mistranslation. These secondary mutations are primarily in single-stranded regions or substitute G:U base pairs for Watson–Crick pairs. Many of the variants are more toxic at low temperature and upon impairing the rapid tRNA decay pathway. We suggest that the majority of the secondary mutations affect the stability of the tRNA in cells. The temperature sensitivity of the tRNAs allows conditional mistranslation. Proteomic analysis demonstrated that tRNA
Ser
variants mistranslate to different extents with diminished growth correlating with increased mistranslation. When combined with a secondary mutation, other anticodon substitutions allow serine mistranslation at additional nonserine codons. These mistranslating tRNAs have applications in synthetic biology, by creating “statistical proteins,” which may display a wider range of activities or substrate specificities than the homogenous form.
Hydrogen sulfide (H
2
S) is an endogenously produced signaling molecule that can be cytoprotective, especially in conditions of ischemia/reperfusion injury. However, H
2
S is also toxic, and ...unregulated accumulation or exposure to environmental H
2
S can be lethal. In
Caenorhabditis elegans
, the hypoxia inducible factor (
hif-1
) coordinates the initial transcriptional response to H
2
S, and is essential to survive exposure to low concentrations of H
2
S. We performed a forward genetic screen to identify mutations that suppress the lethality of
hif-1
mutant animals in H
2
S. The mutations we recovered are specific for H
2
S, as they do not suppress embryonic lethality or reproductive arrest of
hif-1
mutant animals in hypoxia, nor can they prevent the death of
hif-1
mutant animals exposed to hydrogen cyanide. The majority of
hif-1
suppressor mutations we recovered activate the
skn-1
/Nrf2 transcription factor. Activation of SKN-1 by
hif-1
suppressor mutations increased the expression of a subset of H
2
S-responsive genes, consistent with previous findings that
skn-1
plays a role in the transcriptional response to H
2
S. Using transgenic rescue, we show that overexpression of a single gene,
rhy-1
, is sufficient to protect
hif-1
mutant animals in H
2
S. The
rhy-1
gene encodes a predicated O-acyltransferase enzyme that has previously been shown to negatively regulate HIF-1 activity. Our data indicate that RHY-1 has novel,
hif-1
independent, function that promotes survival in H
2
S.
F
ST
is a statistic that is frequently used to analyze population structure. Recent work has shown that
F
ST
depends strongly on the underlying genetic diversity of a locus from which it is ...computed...
The population-genetic statistic
F
S
T
is used widely to describe allele frequency distributions in subdivided populations. The increasing availability of DNA sequence data has recently enabled computations of
F
S
T
from sequence-based “haplotype loci.” At the same time, theoretical work has revealed that
F
S
T
has a strong dependence on the underlying genetic diversity of a locus from which it is computed, with high diversity constraining values of
F
S
T
to be low. In the case of haplotype loci, for which two haplotypes that are distinct over a specified length along a chromosome are treated as distinct alleles, genetic diversity is influenced by haplotype length: longer haplotype loci have the potential for greater genetic diversity. Here, we study the dependence of
F
S
T
on haplotype length. Using a model in which a haplotype locus is sequentially incremented by one biallelic locus at a time, we show that increasing the length of the haplotype locus can either increase or decrease the value of
F
S
T
, and usually decreases it. We compute
F
S
T
on haplotype loci in human populations, finding a close correspondence between the observed values and our theoretical predictions. We conclude that effects of haplotype length are valuable to consider when interpreting
F
S
T
calculated on haplotypic data.
Introduction To investigate the prevalence of OSA among civil servants undergoing annual physical examination, active CPAP intervention was performed in diagnosed OSA patients,provide experience for ...OSA population control. Methods The method of cluster sampling is adopted, investigate a government official in guangdong province who underwent an annual health check-up between July and December 2017. The survey includes general information, clinical history, living habits (smoking, alcohol consumption, exercise frequency), sleep specific questionnaire, physical examination, OSA screening and diagnosis. Patients diagnosed with OSA were given free CPAP treatment. Results 1036 subjects (799 males and 237 females) completed the investigation and were included in the analysis. 22.0% (228/1036) were regarded as high-risk OSA (HR-OSA), 72 rejected home sleep test(HST), while 156 received, and 103 diagnosed as OSA. The prevalence of OSA in HR-OSA was 66.0% (103/156), of which mild, moderate, and severe was 40.2% (41/103), 33.3% (35/103), 26.5% (27/103) respectively. The prevalence of OSA was 9.9% (103/1036). 99.1% (226/228) patient in HR-OSA group have never been diagnosed. Free auto CPAP treatment was given to all OSA. Only 55.3% (57/103) patients received initial treatment. 29.8% (17/57) patients gave up in 1 week, the mainly reasons of rejecting further therapy were nose discomfort, insomnia and suffocating feeling. Conclusion There is a high risk of OSA and a high prevalence of OSA in the annual physical examination of civil servants. Most people have never been diagnosed with OSA, even with free CPAP treatment, the treatment rate was low and compliance was gradually reduced. Support (If Any) 1.National Natural Science Foundation of China(NSFC81870077) 2.Public Welfare Research and Capacity Building of Guangdong Province(2016A020216030)
Abstract
Natural and experimental systems have failed to universally demonstrate a trade-off between generalism and specialism. When a trade-off does occur it is difficult to attribute its cause to ...antagonistic pleiotropy without dissecting the genetic basis of adaptation, and few previous experiments provide these genetic data. Here we investigate the evolution of expanded host range (generalism) in the RNA virus Φ6, an experimental model system allowing adaptive mutations to be readily identified. We isolated 10 spontaneous host range mutants on each of three novel Pseudomonas hosts and determined whether these mutations imposed fitness costs on the standard laboratory host. Sequencing revealed that each mutant had one of nine nonsynonymous mutations in the Φ6 gene P3, important in host attachment. Seven of these nine mutations were costly on the original host, confirming the existence of antagonistic pleiotropy. In addition to this genetically imposed cost, we identified an epigenetic cost of generalism that occurs when phage transition between host types. Our results confirm the existence in Φ6 of two costs of generalism, genetic and environmental, but they also indicate that the cost is not always large. The possibility for cost-free niche expansion implies that varied ecological conditions may favor host shifts in RNA viruses.
Reinterpreting what Bigfoot researchers commonly call "class B" reports (i.e., reports of events consistent with alleged Bigfoot behavior but lacking an actual sighting) as potential poltergeist ...phenomena, Cutchin produces a laundry list of ostensible similarities, including "thrown stones, raps, disembodied voices, anomalous odors, frightened pets, apports, electrical interference, and anomalous lights" (p.10). ...in place of the standard rock-throwing, a behavior both reported in numerous Bigfoot eyewitness accounts and also consistent with known primate behavior, certain witnesses reported being showered instead with tiny pebbles. Rather than shrug our shoulders at where the potential line, if any, may be drawn between possible Bigfoot and poltergeist experiences, I encourage parapsychological focus on cases fitting this particular profile, which is almost certainly not reconcilable with any conceivably natural Bigfoot species.
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