A fundamental feature of immune systems is the ability to distinguish pathogenic from self and commensal elements, and to attack the former but tolerate the latter. Prokaryotic CRISPR-Cas immune ...systems defend against phage infection by using Cas nucleases and small RNA guides that specify one or more target sites for cleavage of the viral genome. Temperate phages include viruses that can integrate into the bacterial chromosome, and they can carry genes that provide a fitness advantage to the lysogenic host. However, CRISPR-Cas targeting that relies strictly on DNA sequence recognition provides indiscriminate immunity both to lytic and lysogenic infection by temperate phages-compromising the genetic stability of these potentially beneficial elements altogether. Here we show that the Staphylococcus epidermidis CRISPR-Cas system can prevent lytic infection but tolerate lysogenization by temperate phages. Conditional tolerance is achieved through transcription-dependent DNA targeting, and ensures that targeting is resumed upon induction of the prophage lytic cycle. Our results provide evidence for the functional divergence of CRISPR-Cas systems and highlight the importance of targeting mechanism diversity. In addition, they extend the concept of 'tolerance to non-self' to the prokaryotic branch of adaptive immunity.
We construct the Green–Schwarz terms of six-dimensional supergravity theories on spacetimes with non-trivial topology and gauge bundle. We prove the cancellation of all global gauge and gravitational ...anomalies for theories with gauge groups given by products of
U
(
n
),
SU
(
n
) and
Sp
(
n
) factors, as well as for
E
8
. For other gauge groups, anomaly cancellation is equivalent to the triviality of a certain 7-dimensional spin topological field theory. We show in the case of a finite Abelian gauge group that there are residual global anomalies imposing constraints on the 6d supergravity. These constraints are compatible with the known F-theory models. Interestingly, our construction requires that the gravitational anomaly coefficient of the 6d supergravity theory is a characteristic element of the lattice of string charges, a fact true in six-dimensional F-theory compactifications but that until now was lacking a low-energy explanation. We also discover a new anomaly coefficient associated with a torsion characteristic class in theories with a disconnected gauge group.
Much is known about the serious neurological effects of gluten ingestion in coeliac disease patients, such as sporadic ataxia and peripheral neuropathy, although the causal links to gluten are still ...under debate. However, such disorders are observed in only a small percentage of coeliac patients. Much less is known about the transient cognitive impairments to memory, attention, executive function, and the speed of cognitive processing reported by the majority of patients with coeliac disease. These mild degradations of cognitive functions, referred to as “brain fog,” are yet to be formally recognized as a medical or psychological condition. However, subtle tests of cognitive function are measurable in untreated patients with coeliac disease and improve over the first 12 months' therapy with a gluten‐free diet. Such deficits also occur in patients with Crohn's disease, particularly in association with systemic inflammatory activity. Thus, cognitive impairments associated with brain fog are psychologically and neurologically real and improve with adherence to a gluten‐free diet. There is not yet sufficient evidence to provide a definitive account of the mechanism by which gluten ingestion causes the impairments to cognitive function associated with brain fog, but current evidence suggests that it is more likely that the causal factor is not directly related to exposure to gluten.
Comparative political economy (CPE) has robustly examined the political and institutional determinants of income inequality. However, the study of wealth, which is more unequally distributed than ...income, has been largely understudied within CPE. Using new data from the World Income Database (WID), this article examines how economic, political and institutional dynamics shape wealth-to-income ratios within Western European and OECD countries. It is found that the political and institutional determinants that affect income inequality have no short- or long-run effects on the wealth-to-income ratio. Rather, the rise in wealth-to-income ratios is driven by rising housing prices, as well as price changes in other financial assets, not home ownership or national saving rates. The article concludes by examining how the changing dynamics of housing prices and wealth inequality will increasingly shape intergenerational - and associated class-based - political conflict in Western Europe.
The threat associated with chemical warfare agents (CWAs) motivates the development of new materials to provide enhanced protection with a reduced burden. Metal–organic frame‐works (MOFs) have ...recently been shown as highly effective catalysts for detoxifying CWAs, but challenges still remain for integrating MOFs into functional filter media and/or protective garments. Herein, we report a series of MOF–nanofiber kebab structures for fast degradation of CWAs. We found TiO2 coatings deposited via atomic layer deposition (ALD) onto polyamide‐6 nanofibers enable the formation of conformal Zr‐based MOF thin films including UiO‐66, UiO‐66‐NH2, and UiO‐67. Cross‐sectional TEM images show that these MOF crystals nucleate and grow directly on and around the nanofibers, with strong attachment to the substrates. These MOF‐functionalized nanofibers exhibit excellent reactivity for detoxifying CWAs. The half‐lives of a CWA simulant compound and nerve agent soman (GD) are as short as 7.3 min and 2.3 min, respectively. These results therefore provide the earliest report of MOF–nanofiber textile composites capable of ultra‐fast degradation of CWAs.
Skewering nerve agents: Conformal metal–organic framework (MOF) kebab structures decorated on nanofibers that can degrade chemical warfare agents within minutes are described. These MOF–nanofiber composites show excellent reactivity towards both simulant and nerve agent soman (GD).
The capacity of the Gaussian wiretap channel model is analyzed when there are multiple antennas at the sender, intended receiver and eavesdropper. The associated channel matrices are fixed and known ...to all the terminals. A computable characterization of the secrecy capacity is established as the saddle point solution to a minimax problem. The converse is based on a Sato-type argument used in other broadcast settings, and the coding theorem is based on Gaussian wiretap codebooks. At high signal-to-noise ratio (SNR), the secrecy capacity is shown to be attained by simultaneously diagonalizing the channel matrices via the generalized singular value decomposition, and independently coding across the resulting parallel channels. The associated capacity is expressed in terms of the corresponding generalized singular values. It is shown that a semi-blind "masked" multi-input multi-output (MIMO) transmission strategy that sends information along directions in which there is gain to the intended receiver, and synthetic noise along directions in which there is not, can be arbitrarily far from capacity in this regime. Necessary and sufficient conditions for the secrecy capacity to be zero are provided, which simplify in the limit of many antennas when the entries of the channel matrices are independent and identically distributed. The resulting scaling laws establish that to prevent secure communication, the eavesdropper needs three times as many antennas as the sender and intended receiver have jointly, and that the optimum division of antennas between sender and intended receiver is in the ratio of 2:1.
Promotion of physical activity is a priority for health agencies. We searched for reviews of physical activity interventions, published between 2000 and 2011, and identified effective, promising, or ...emerging interventions from around the world. The informational approaches of community-wide and mass media campaigns, and short physical activity messages targeting key community sites are recommended. Behavioural and social approaches are effective, introducing social support for physical activity within communities and worksites, and school-based strategies that encompass physical education, classroom activities, after-school sports, and active transport. Recommended environmental and policy approaches include creation and improvement of access to places for physical activity with informational outreach activities, community-scale and street-scale urban design and land use, active transport policy and practices, and community-wide policies and planning. Thus, many approaches lead to acceptable increases in physical activity among people of various ages, and from different social groups, countries, and communities.
Virtually all well-documented remains of early domestic dog (Canis familiaris) come from the late Glacial and early Holocene periods (ca. 14,000-9000 calendar years ago, cal BP), with few putative ...dogs found prior to the Last Glacial Maximum (LGM, ca. 26,500-19,000 cal BP). The dearth of pre-LGM dog-like canids and incomplete state of their preservation has until now prevented an understanding of the morphological features of transitional forms between wild wolves and domesticated dogs in temporal perspective.
We describe the well-preserved remains of a dog-like canid from the Razboinichya Cave (Altai Mountains of southern Siberia). Because of the extraordinary preservation of the material, including skull, mandibles (both sides) and teeth, it was possible to conduct a complete morphological description and comparison with representative examples of pre-LGM wild wolves, modern wolves, prehistoric domesticated dogs, and early dog-like canids, using morphological criteria to distinguish between wolves and dogs. It was found that the Razboinichya Cave individual is most similar to fully domesticated dogs from Greenland (about 1000 years old), and unlike ancient and modern wolves, and putative dogs from Eliseevichi I site in central Russia. Direct AMS radiocarbon dating of the skull and mandible of the Razboinichya canid conducted in three independent laboratories resulted in highly compatible ages, with average value of ca. 33,000 cal BP.
The Razboinichya Cave specimen appears to be an incipient dog that did not give rise to late Glacial-early Holocene lineages and probably represents wolf domestication disrupted by the climatic and cultural changes associated with the LGM. The two earliest incipient dogs from Western Europe (Goyet, Belguim) and Siberia (Razboinichya), separated by thousands of kilometers, show that dog domestication was multiregional, and thus had no single place of origin (as some DNA data have suggested) and subsequent spread.
The ability to maintain quiescence is critical for the long-term maintenance of a functional stem cell pool. To date, the epigenetic and transcriptional characteristics of quiescent stem cells and ...how they change with age remain largely unknown. In this study, we explore the chromatin features of adult skeletal muscle stem cells, or satellite cells (SCs), which reside predominantly in a quiescent state in fully developed limb muscles of both young and aged mice. Using a ChIP-seq approach to obtain global epigenetic profiles of quiescent SCs (QSCs), we show that QSCs possess a permissive chromatin state in which few genes are epigenetically repressed by Polycomb group (PcG)-mediated histone 3 lysine 27 trimethylation (H3K27me3), and a large number of genes encoding regulators that specify nonmyogenic lineages are demarcated by bivalent domains at their transcription start sites (TSSs). By comparing epigenetic profiles of QSCs from young and old mice, we also provide direct evidence that, with age, epigenetic changes accumulate and may lead to a functional decline in quiescent stem cells. These findings highlight the importance of chromatin mapping in understanding unique features of stem cell identity and stem cell aging.
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•Chromatin modification pattern on myogenic regulatory factor genes in QSCs•Chromatin modification pattern on myogenic regulatory factor genes in QSCs•Increase in H3K27me3 across the genome in adult QSCs with age•Decrease of histone expression in adult QSCs with age
The comprehensive transcriptional and chromatin modification profile of an adult quiescent stem cell population, skeletal muscle satellite cells, is now examined by Rando and colleagues. The authors characterize changes associated with satellite cell activation and aging, providing direct evidence for global changes in histone modifications in adult stem cells with age.
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