The Routledge Companion to Media and Race serves as a comprehensive guide for scholars, students, and media professionals who seek to understand the key debates about the impact of media messages on ...racial attitudes and understanding. Broad in scope and richly presented from a diversity of perspectives, the book is divided into three sections: first, it summarizes the theoretical approaches that scholars have adopted to analyze the complexities of media messages about race and ethnicity, from the notion of "representation" to more recent concepts like Critical Race Theory. Second, the book reviews studies related to a variety of media, including film, television, print media, social media, music, and video games. Finally, contributors present a broad summary of media issues related to specific races and ethnicities and describe the relationship of the study of race to the study of gender and sexuality.
The use of nanoparticles as formulation components of topical drug delivery systems for the skin has been widely investigated in the literature. Because of the conflicting conclusions resulting from ...these studies concerning the ultimate disposition of the nanoparticles employed, the research presented in this paper has been designed to evaluate objectively the fate of such structures when administered to mammalian skin. Confocal microscopy images of skin exposed to nanoparticles have therefore been assessed by quantitative statistical analysis. Sebum on the skin surface was naturally fluorescent and clearly defined the outermost part of the cutaneous barrier. Fluorescent polystyrene nanoparticles applied in aqueous suspension could infiltrate only the stratum disjunctum, i.e., skin layers in the final stages of desquamation. This minimal uptake was independent of contact time (up to 16h) and of nanoparticle size tested (20–200nm). When skin barrier function was modestly compromised, the nanoparticles remained incapable of penetration beyond the most superficial layers, corresponding to a depth of 2–3μm, of the stratum corneum (the outermost, 15–20μm skin layer). Overall, these results demonstrate objectively and semi-quantitatively that nanoparticles contacting intact, and even partially damaged, skin cannot penetrate beyond the superficial layers of the barrier, and are highly unlikely, therefore, to reach the viable cells of the epidermis or beyond. It follows that nanoparticulate-based, topical delivery systems may prove useful as skin surface reservoirs from which controlled drug release over time may be achieved.
Disposition of fluorescent nanoparticles on skin surface close to a hair emerging from its follicle. Particles are green, skin autofluorescence is red, sebum coating hair shaft is blue. Display omitted
DNA mismatch repair (MMR) increases replication fidelity by eliminating mispaired bases resulting from replication errors. In Saccharomyces cerevisiae, mispairs are primarily detected by the ...Msh2-Msh6 complex and corrected following recruitment of the Mlh1-Pms1 complex. Here, we visualized functional fluorescent versions of Msh2-Msh6 and Mlh1-Pms1 in living cells. We found that the Msh2-Msh6 complex is an S phase component of replication centers independent of mispaired bases; this localized pool accounted for 10%–15% of MMR in wild-type cells but was essential for MMR in the absence of Exo1. Unexpectedly, Mlh1-Pms1 formed nuclear foci that, although dependent on Msh2-Msh6 for formation, rarely colocalized with Msh2-Msh6 replication-associated foci. Mlh1-Pms1 foci increased when the number of mispaired bases was increased; in contrast, Msh2-Msh6 foci were unaffected. These findings suggest the presence of replication machinery-coupled and -independent pathways for mispair recognition by Msh2-Msh6, which direct formation of superstoichiometric Mlh1-Pms1 foci that represent sites of active MMR.
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► S. cerevisiae Msh2-Msh6 is present in DNA replication factory foci ► Lagging-strand DNA mismatch repair (MMR) preferentially requires Exo1 ► Msh2-Msh6 foci-independent MMR is preferentially dependent on Exo1 ► Pms1 foci are active in MMR and contain substoichiometric amounts of Msh2-Msh6
In vivo imaging reveals that two mismatch repair protein complexes involved in mismatch repair have distinct functions, as one recognizes mispaired bases and one mediates active repair. The recognition complex is coupled to the DNA replication machinery, facilitating the detection of mismatches occurring during DNA synthesis.
In humans, males have lower recombination rates than females over the majority of the genome, but the opposite is usually true near the telomeres. These broad-scale differences have been known for ...decades, yet little is known about differences at the fine scale. By combining data sets, we have collected recombination events from over 100,000 meioses and have constructed sex-specific genetic maps at a previously unachievable resolution. Here we show that, although a substantial fraction of the genome shows some degree of sexually dimorphic recombination, the vast majority of hotspots are shared between the sexes, with only a small number of putative sex-specific hotspots. Wavelet analysis indicates that most of the differences can be attributed to the fine scale, and that variation in rate between the sexes can mostly be explained by differences in hotspot magnitude, rather than location. Nonetheless, known recombination-associated genomic features, such as THE1B repeat elements, show systematic differences between the sexes.
Mitochondrial transcription factor A (mtTFA, mtTF1, TFAM) is an essential protein that binds mitochondrial DNA (mtDNA) with and without sequence specificity to regulate both mitochondrial ...transcription initiation and mtDNA copy number. The abundance of mtDNA generally reflects TFAM protein levels; however, the precise mechanism(s) by which this occurs remains a matter of debate. Data suggest that the usage of mitochondrial promoters is regulated by TFAM dosage, allowing TFAM to affect both gene expression and RNA priming for first strand mtDNA replication. Additionally, TFAM has a non-specific DNA binding activity that is both cooperative and high affinity. TFAM can compact plasmid DNA in vitro, suggesting a structural role for the non-specific DNA binding activity in genome packaging. This review summarizes TFAM-mtDNA interactions and describes an emerging view of TFAM as a multipurpose coordinator of mtDNA transactions, with direct consequences for the maintenance of gene expression and genome copy number. This article is part of a Special Issue entitled: Mitochondrial Gene Expression.
► We review TFAM–DNA interactions, including specificity, affinity, bending, and cooperativity. ► We review proposed mechanisms of TFAM regulation of mtDNA copy number. ► We propose a model in which TFAM dimerization, DNA looping, and cooperativity impact mtDNA packaging and promoter activity.
Accurate segregation of the replicated genome requires chromosome biorientation on the spindle. Biorientation is ensured by Aurora B kinase (Ipl1), a member of the four-subunit chromosomal passenger ...complex (CPC). Localization of the CPC to the inner centromere is central to the current model for how tension ensures chromosome biorientation: kinetochore-spindle attachments that are not under tension remain close to the inner centromere and are destabilized by Aurora B phosphorylation, whereas kinetochores under tension are pulled away from the influence of Aurora B, stabilizing their microtubule attachments. Here we show that an engineered truncation of the Sli15 (known as INCENP in humans) subunit of budding yeast CPC that eliminates association with the inner centromere nevertheless supports proper chromosome segregation during both mitosis and meiosis. Truncated Sli15 suppresses the deletion phenotypes of the inner-centromere-targeting proteins survivin (Bir1), borealin (Nbl1), Bub1 and Sgo1 (ref. 6). Unlike wild-type Sli15, truncated Sli15 localizes to pre-anaphase spindle microtubules. Premature targeting of full-length Sli15 to microtubules by preventing Cdk1 (also known as Cdc28) phosphorylation also suppresses the inviability of Bir1 deletion. These results suggest that activation of Aurora B kinase by clustering either on chromatin or on microtubules is sufficient for chromosome biorientation.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•Amelanchier, Malacomeles and Peraphyllulm constitute a strongly supported clade.•Great incongruences are detected in the plastid and nuclear phylogenies.•Chloroplast capture was ...inferred in the origin of Malacomeles and Peraphyllulm.•Separate generic status of Amelanchier, Malacomeles and Peraphyllulm is supported.
The Amelanchier-Malacomeles-Peraphyllum (AMP) clade consists of ca. 26 species distributed in North and Central America, Europe, Asia, and northwestern Africa. While molecular and morphological data strongly support this clade, relationships of its genera are uncertain. Support for the monophyly of Amelanchier and for the phylogenetic positions of Malacomeles and Peraphyllum has varied between studies. Our goals were to reconstruct a robust phylogeny of the AMP clade in the framework of Maleae and clarify the phylogenetic placements of Malacomeles and Peraphyllum. This study employs sequences of the whole plastome and nuclear ribosomal DNA (nrDNA) repeats assembled using genome skimming with 131 samples representing 115 species in 31 genera of Rosaceae, especially Maleae. Maximum likelihood (ML) and Bayesian analysis (BI) of whole plastome datasets strongly supported Amelanchier as not monophyletic, with Peraphyllum sister to eastern North American Amelanchier and Malacomeles sister to the western North American-Eurasian Amelanchier. In contrast, nrDNA recovered the monophyly of Amelanchier, with Peraphyllum sister to Amelanchier and Malacomeles sister to the Amelanchier-Peraphyllum clade. The strong topological conflicts between plastome and nrDNA phylogenies of Peraphyllum and of Malacomeles are best explained by ancient chloroplast capture that occurred in SW North America.
Background:
Although heparin has previously been the anticoagulant of choice during mechanical circulatory support (MCS), there is a lack of consistency in dose-response in pediatric patients. ...Bivalirudin offers more consistent dose-response in adults; however, there are limited data for pediatrics use.
Objective:
The purpose was to characterize the usage, dosage, and safety profile of bivalirudin when used for pediatric MCS in a tertiary care pediatric hospital.
Methods:
A retrospective review of pediatric patients receiving bivalirudin for extracorporeal membrane oxygenation/ventricular assist device (ECMO/VAD) anticoagulation was conducted. The primary outcome was the average dose of bivalirudin. Additional outcomes included initial and maximum bivalirudin dose, time to first therapeutic activated partial thromboplastin time (aPTT), time within goal aPTT range, bleeding and clotting complications, and cost. Data were compared between ECMO and VAD patients.
Results:
Thirty-four patients were included. The median dose of bivalirudin was 0.37 mg/kg/h (interquartile range IQR = 0.21-0.56), with a maximum dose of 0.62 mg/kg/h (IQR = 0.33-0.91). VAD patients had a higher median and maximum dose as compared with ECMO patients. Patients achieved their therapeutic goal in a median of 6.1 hours and averaged 61.9% time within therapeutic aPTT. One patient had significant hemorrhage, whereas 3 patients had clotting requiring a circuit change. Bivalirudin acquisition cost was higher than heparin.
Conclusion and Relevance:
Bivalirudin dosing in ECMO and VAD patients is consistent with dosing seen in previous reports but may be higher in VAD patients. Comparative studies between heparin and bivalirudin are necessary to compare cost-effective outcomes for pediatric patients.
Genetic evidence has implicated multiple pathways in eukaryotic DNA mismatch repair (MMR) downstream of mispair recognition and Mlh1-Pms1 recruitment, including Exonuclease 1 (Exo1)-dependent and ...-independent pathways. We identified 14 mutations in POL30, which encodes PCNA in Saccharomyces cerevisiae, specific to Exo1-independent MMR. The mutations identified affected amino acids at three distinct sites on the PCNA structure. Multiple mutant PCNA proteins had defects either in trimerization and Msh2-Msh6 binding or in activation of the Mlh1-Pms1 endonuclease that initiates excision during MMR. The latter class of mutations led to hyperaccumulation of repair intermediate Mlh1-Pms1 foci and were enhanced by an msh6 mutation that disrupted the Msh2-Msh6 interaction with PCNA. These results reveal a central role for PCNA in the Exo1-independent MMR pathway and suggest that Msh2-Msh6 localizes PCNA to repair sites after mispair recognition to activate the Mlh1-Pms1 endonuclease for initiating Exo1-dependent repair or for driving progressive excision in Exo1-independent repair.
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•PCNA mutants disrupt Exo1-independent MMR by two mechanisms•Mutants either poorly bind Msh2-Msh6 or poorly activate the Mlh1-Pms1 endonuclease•Activation mutations are enhanced by loss of the interaction with Msh2-Msh6•Msh2-Msh6 promotes excision by localizing PCNA for Mlh1-Pms1 activation
DNA mismatch repair (MMR) involves Exo1-dependent and -independent pathways for excision of the mispair. Using S. cerevisiae, Goellner et al. identified mutations in the gene encoding PCNA specific to the Exo1-independent pathway and show that PCNA binding to Msh2-Msh6 and activation of the Mlh1-Pms1 endonuclease are critical to Exo1-independent MMR.
More than a quarter of a century after the first metal template synthesis of a 2catenane in Strasbourg, there now exists a plethora of strategies available for the construction of mechanically bonded ...and entwined molecular level structures. Catenanes, rotaxanes, knots and Borromean rings have all been successfully accessed by methods in which metal ions play a pivotal role. Originally metal ions were used solely for their coordination chemistry; acting either to gather and position the building blocks such that subsequent reactions generated the interlocked products or by being an integral part of the rings or “stoppers” of the interlocked assembly. Recently the role of the metal has evolved to encompass catalysis: the metal ions not only organize the building blocks in an entwined or threaded arrangement but also actively promote the reaction that covalently captures the interlocked structure. This Review outlines the diverse strategies that currently exist for forming mechanically bonded molecular structures with metal ions and details the tactics that the chemist can utilize for creating cross‐over points, maximizing the yield of interlocked over non‐interlocked products, and the reactions‐of‐choice for the covalent capture of threaded and entwined intermediates.
Knots and crossings: Metal ions have been employed in diverse ways in the assembly of mechanically interlocked architectures (see scheme). The range of product topologies spans from catenanes and rotaxanes to trefoil knots, Solomon links, and Borromean rings.
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