bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebrospinal fluid tau fragment correlates with tau PET: a candidate biomarker for tangle pathology
Authors: Blennow Kaj , Chen Chun , Cicognola Claudia , Wildsmith Kristin R , Manser Paul T , Bohorquez Sandra M Sanabria , Zhang Zhentao , Xie Boer , Peng Junmin , Hansson Oskar , Kvartsberg Hlin , Portelius Erik , Zetterberg Henrik , Lashley Tammaryn , Brinkmalm Gunnar , Kerchner Geoffrey A , Weimer Robby M , Ye Keqiang , Höglund Kina
Published: October 2019

To date, there is no validated fluid biomarker for tau pathology in Alzheimer’s disease, with contradictory results from studies evaluating the correlation between phosphorylated tau in CSF with tau PET imaging. Tau protein is subjected to proteolytic processing into fragments before being secreted to the CSF. A recent study suggested that tau cleavage after amino acid 368 by asparagine endopeptidase (AEP) is upregulated in Alzheimer’s disease. We used immunoprecipitation followed by mass spectrometric analyses to evaluate the presence of tau368 species in CSF. A novel Simoa® assay for quantification of tau368 in CSF was developed, while total tau (t-tau) was measured by ELISA and the presence of tau368 in tangles was evaluated using immunohistochemistry. The diagnostic utility of tau368 was first evaluated in a pilot study (Alzheimer’s disease = 20, control = 20), then in a second cohort where the IWG-2 biomarker criteria were applied (Alzheimer’s disease = 37, control = 45), and finally in a third cohort where the correlation with 18F-GTP1 tau PET was evaluated (Alzheimer’s disease = 38, control = 11). The tau368/t-tau ratio was significantly decreased in Alzheimer’s disease (P < 0.001) in all cohorts. Immunohistochemical staining demonstrated that tau fragments ending at 368 are present in tangles. There was a strong negative correlation between the CSF tau368/t-tau ratio and 18F-GTP1 retention. Our data suggest that tau368 is a tangle-enriched fragment and that the CSF ratio tau368/t-tau reflects tangle pathology. This novel tau biomarker could be used to improve diagnosis of Alzheimer’s disease and to facilitate the development of drug candidates targeting tau pathology. Furthermore, future longitudinal studies will increase our understanding of tau pathophysiology in Alzheimer’s disease and other tauopathies.
Revisiting the concept of liquidity in liquidity preference
Authors: Culham James
Published: October 2019

This paper revisits Keynes’s theory of liquidity preference to emphasise its reliance on liquidity. By clarifying the meaning of ‘liquidity’ in the context of the theory, it is argued that liquidity preference is not based on the demand for money, the most tradable asset, or a theory of bearishness. Instead, liquidity preference represents a demand for price-protected (capital-safe) assets, most directly inside and outside money, but also cash-equivalent quasi-money such as self-liquidating assets and security repurchase agreements (repo). The theory of liquidity preference explains that the public is willing to forgo interest income to hold short-term price-protected assets due to the capital and price uncertainty associated with relying on market liquidity, or how easy it is to convert an asset into money. It follows that the rate of interest is a monetary phenomenon and is determined independently of saving and investment.
Deletion of IL-6 Exacerbates Colitis and Induces Systemic Inflammation in IL-10-Deficient Mice
Authors: Ye Mei , Joosse Maria E , Liu Ling , Sun Yu , Dong Ying , Cai Changchun , Song Zhenmei , Zhang Jennifer , Brant Steven R , Lazarev Mark , Li Xuhang
Published: October 2019

Background and Aims

Interleukin 6 [IL-6] or its receptor is currently a candidate for targeted biological therapy of inflammatory bowel disease [IBD]. Thus, a comprehensive understanding of the consequences of blocking IL-6 is imperative. We investigated this by evaluating the effects of IL-6 deletion on the spontaneous colitis of IL-10-deficient mice [IL-10−/−].

Methods

IL-6/IL-10 double-deficient mice [IL-6−/−/IL-10−/−] were generated and analysed for intestinal inflammation, general phenotypes and molecular/biochemical changes in the colonic mucosa compared with wild-type and IL-10−/− mice.

Results

Unexpectedly, the IL-6−/−/IL-10−/− mice showed more pronounced gut inflammation and earlier disease onset than IL-10−/− mice, both locally [colon and small bowel] and systemically [splenomegaly, ulcerative dermatitis, leukocytosis, neutrophilia and monocytosis]. IL-6−/−/IL-10−/− mice exhibited elevations of multiple cytokines [IL-1β, IL-4, IL-12, TNFα] and chemokines [MCP-1 and MIG], but not IFN-γ [Th1], IL-17A and IL-17G [Th17], or IL-22 [Th22]. FOXP3 and TGF-β, two key factors for regulatory T [Treg] cell differentiation, were significantly down-regulated in the colonic mucosa, but not in the thymus or mesenteric lymph nodes, of IL-6−/−/IL-10−/− mice. CTLA-4 was diminished while iNOS was up-regulated in the colonic mucosa of IL-6−/−/IL-10−/− mice.

Conclusion

In IL-10−/− mice, complete IL-6 blockade significantly aggravates gut inflammation, at least in part by suppressing Treg/CTLA-4 and promoting the IL-1β/Th2 pathway. In addition, the double mutant exhibits signs of severe systemic inflammation. Our data define a new function of IL-6 and suggest that caution should be exercised when targeting IL-6 in IBD patients, particularly those with defects in IL-10 signalling.
Impact of orthodontic-surgical treatment on quality of life: a meta-analysis
Authors: de Araujo Cristiano Miranda , Schroder Angela Graciela Deliga , de Araujo Bianca Marques de Mattos , Cavalcante-Leão Bianca L , Stechman-Neto José , Zeigelboim Bianca Simone , Santos Rosane Sampaio , Guariza-Filho Odilon
Published: October 2019

Background

Orthognathic surgery involves a change in the patient’s functional and aesthetic aspects.

Objective

The objective was to answer the following focused question: what is the impact on quality of life (QoL; aesthetic, function, social, and psychological aspects) in patients undergoing orthodontic-surgical treatment?

Search methods

Appropriate word combinations and truncations were selected and tailored specifically for each electronic database: PubMed/Medline, Scopus, Web of Science, PsycInfo, and Latin American and Caribbean Health Sciences Literature and gray literature.

Selection criteria

Studies that met the following criteria was included: patients with dentofacial deformity (P); surgical correction through orthodontic-surgical treatment (E/I); before orthodontic-surgical treatment or patients with no dentofacial deformity (C); QoL (O); cross-sectional, cohort, case-control and randomized or non-randomized clinical trial (S).

Data collection and analysis

In phase 1, two reviewers independently reviewed the titles and abstracts of all references. All articles that did not meet the inclusion criteria were excluded. In phase 2, the same reviewers completely read the selected articles independently.

Results

A total of 2879 articles were retrieved during the final database search. Fifty-two articles were selected for full reading, of which 16 were excluded, resulting in 36 included articles. The meta-analysis was performed using 13 of the selected studies. When comparing the period before any treatment with the post-operative period of 4–8 weeks, there was an association only for facial aesthetics (mean difference = 3.00; 95 per cent confidence interval = 1.10–4.89; inconsistency index = 63 per cent). The comparison between the period before any treatment with the 6 month post-operative period showed an improved QoL in all of the domains evaluated and, when comparing data after the orthodontic-surgical preparation (before surgery) and after 5–12 months of surgery, there was also statistical significance with an increased QoL for all of the domains evaluated.

Conclusions

In conclusion, based on the results of this systematic review and meta-analysis, the evidence suggests an improvement in the QoL of patients undergoing orthodontic-surgical treatment regarding aesthetic, functional, social, and psychological aspects.

Registration

CRD42017069495
Authenticity and motivation: a writing for publication experience
Authors: Banegas Darío Luis , Roberts Grisel , Colucci Romina , Sarsa Betina Ana
Published: October 2019

Framed in exploratory action research, this article reports on an experience carried out at an initial English teacher education (IELTE) programme in Argentina. A group of four tutors noticed their student-teachers’ demotivation to complete written coursework. On exploring this issue, it was found that lack of authenticity of audience in writing tasks acted as a demotivation factor. The tutors adapted their teaching practices to engage the student-teachers in a writing for publication project organized by an Argentinian teacher association in 2018. To understand the effects of this experience on the student-teachers’ motivation, data were collected through individual interviews, in-class group discussions, pair-work tasks with the student-teachers, and through notes taken during tutors’ meetings. Findings show that while authenticity of audience acted as a motivating factor with more advanced student-teachers, most student-teachers and tutors engaged in motivational synergy triggered by a change in tutors’ teaching practices given the possibility of publishing.
Feasibility and acceptability of an intervention for enhancing reintegration in adults with experience of homelessness
Authors: Sundin Eva C , Mrowiec Aleksandra , Bowpitt Graham , Boatman Charlotte A , Williams A J , Sarkar Mustafa , Baguley Thom S
Published: October 2019

Background

Service centres for homeless adults are potential settings for implementation of reintegration interventions. This study aimed to evaluate (i) the acceptability of a group-based programme among individuals from the broad population of homeless people and (ii) if a future study of its feasibility and acceptability for re-housed homeless people is warranted.

Methods

Recruiting participants and intervention facilitators from partnering service centres was thought to improve recruitment and retention, cost-effectiveness and social interactions compared to professional-led interventions. Seven adults with experience of homelessness (three females, four males, mean age 39 years, range 18–63) were recruited to participate in the intervention. The research protocol comprised completion pre/post of scales [Recovering Quality of Life questionnaire; Working Alliance Inventory-short form revised (WAI-SR)] and focus groups, and WAI-SR and focus groups after sessions 3 and 6.

Results

The intervention and research protocols were feasible, with all participants engaging in all sessions, completing all scales and attending all focus groups. The quantitative data demonstrated the feasibility of obtaining practically useful measures of relevant outcomes. In the four focus groups, the intervention received very favourable feedback.

Conclusions

This study demonstrated initial feasibility and acceptability of an intervention that places minimal burden on infrastructure and promotes user autonomy. This is an important advance as there is increasing recognition that the challenge of reintegration is as much a psychological and social problem as a housing problem. If effective, this style of intervention may serve as a template for future interventions with similar populations.
Impact of Plasmid-Encoded H-NS–like Protein on blaNDM-1-Bearing IncX3 Plasmid in Escherichia coli
Authors: Liu Baomo , Shui Lili , Zhou Kai , Jiang Ying , Li Xiaoyu , Guan Jing , Li Qi , Zhuo Chao
Published: October 2019

Background

This study was performed to assess the role of the histone-like nucleoid-structuring (H-NS)–like protein, carried by blaNDM-1-encoding IncX3-type plasmids, in the dissemination of IncX3 plasmids.

Methods

The blaNDM-1-encoding IncX3 plasmids were analyzed using southern blot, conjugation, and competition assays. Virulence was evaluated with a Galleria mellonella infection model. An hns-knockout IncX3 plasmid was also constructed to identify the functions of plasmid-borne H-NS–like protein in Escherichia coli.

Results

The assasys detected blaNDM-1-encoding IncX3-type plasmids with similar fingerprint patterns in all New Delhi metallo-β-lactamase (NDM) 1–producing carbapenem-resistant Enterobacteriaceae. The IncX3 plasmid conferred a fitness advantage to E. coli J53 but had no effect on host virulence. Moreover, the transconjugation frequency of the hns-null IncX3 plasmid pHN330-△hns was increased by 2.5-fold compared with the wild type. This was caused by up-regulation of conjugation-related plasmid-borne genes and the partition-related gene, in the J330-pHN330-△hns strain. In addition, decreased virulence was detected with this variant.

Conclusions

Our results highlight the important role of IncX3 plasmids in the dissemination of blaNDM-1 in south China. Plasmid-encoded H-NS–like protein can inhibit plasmid conjugation, partition, and the expression of related genes, in addition to promoting virulence in the host.
Effects of nest boxes in natural mating colony cages on fear, stress, and feather damage for layer breeders123
Authors: Shi Haipeng , Tong Qin , Zheng Weichao , Tu Jiang , Li Baoming
Published: October 2019

Colony cages are commonly used in China for the natural mating of layer breeders. However, feather pecking (FP) is a major problem in this system, and feather damage mainly due to FP needs to be alleviated. The objective of this study was to investigate the effects of nest boxes provided in colony cages. Each colony cage confined 10 roosters and 90 laying hens. The use of nest boxes as it relates to age, feather damage, sexual behavior, fertility, and fearfulness was evaluated. Thyroid hormones, which are considered to be physiological indicators of various forms of stress in poultry and may be correlated with the quality of feather coverage, were also tested. The control group and the nest box group each had 12 replicates, totaling 24 identical cages. Analyses were conducted using the linear mixed models procedure of SPSS Statistics 22.0. The results showed that the control group had a significantly higher proportion of hens with feather damage to 4 specific body regions (back, rump, tail, and belly) compared to the nest box group (P < 0.05). Increasing the use of the nest boxes took place from weeks 41 to 47 and at 53 wk of age, as seen by the percentage of eggs and number of sitting events in the nests, number of hens using the nests, and frequency of visits. There were no significant differences in fertility, the occurrence of mounting, or full copulation behavior between the 2 groups. Hens in the control group showed a significantly longer duration of tonic immobility at 43, 49, and 55 wk of age (P < 0.05). No significant differences were found between groups for the concentration of triiodothyronine or thyroxine, but a significantly higher concentration of corticosterone was measured in the control group than in the nest box group (P < 0.05). In conclusion, hens with access to nest boxes during the laying period had a decreased FP frequency, fewer damaged feathers, lower plasma corticosterone secretion, and were less fearful. This information contributes to the understanding of the FP behavior and stress sensitivity of layer breeders, which will provide a basis for the development and optimization of the colony cage equipment.
Absence of a microbiome in the midgut trunk of six representative Crustacea
Authors: Martin Gary G , Natha Zain , Henderson Nicola , Bang Sabi , Hendry Hope , Loera Yeraldi
Published: October 2019

It has become a common expectation for an animal’s guts to be a site for bacterial symbiosis, which may play a role in influencing various aspects of physiology including digestion and immune responses. The presence of a microbiome in the digestive tracts of crustaceans has been demonstrated in the past using molecular techniques and has encouraged manipulations including probiotics to enhance growth rates in cultured species. We suggest, however, that bacteria are restricted to the lumen of the gut and separated from the epithelium by the peritrophic matrix, which prevents their establishment as a permanent component of the gut. The peritrophic matrix, found in most arthropods, is a chitinous sheet containing accessory molecules, and is continuously formed by delamination from the epithelium of the midgut such that the actual surface is constantly being cleaned. The lifted layer then surrounds ingested materials, including microbes, in an impenetrable wrapper compartmentalizing digestive and immune functions. The ectoperitrophic space, lying between the peritrophic matrix and the epithelium, was examined in six species representatives of six groups of crustaceans (Branchiopoda, Amphipoda, Copepoda, and Decapoda) for the presence of microbes using light and transmission electron microscopy as well as fluorescent probes for bacteria. The results suggest that a microbiome is lacking in several common groups of crustaceans.
Comprehensive geriatric assessment is correlated to overall survival among gynaecologic oncology patients
Authors: Michaan Nadav , Park Sang Yoon , Lim Myong Cheol
Published: October 2019

Objective

To investigate the correlation of comprehensive geriatric assessment to overall survival among older gynaecologic oncology patients.

Methods

Between 2011 and 2017, patients >70 years had geriatric assessment before treatment. Geriatric assessment included the following tests: Old American resource and services, instrumental activities of daily living, modified Barthels index, mini-mental state examination, geriatric depression scale, mini-nutritional assessment, risk of falling and medication use. Overall survival was calculated for patients’ groups below and above median tests scores. Univariate as well as multivariate analysis was done to evaluate the association between each variable and survival.

Results

About 120 patients had geriatric assessment. Mean patients’ age was 76.4 ± 5. A total of 78 Patients had ovarian cancer, 16 uterine cancer, 17 cervical cancer and 9 had other gynaecologic malignancies. No correlation was found between age, BMI (body mass index) and cancer type to overall survival. Patients with scores below cut-off values of modified Barthels index, instrumental activities of daily living, mini-nutritional assessment and mini-nutritional assessment had significantly shorter overall survival (P = 0.004, 0.031, 0.046 and 0.004, respectively). This remained significant in both univariate and multivariate analysis.

Conclusions

Gynaecologic oncology patients with lower geriatric assessment scores have significantly lower overall survival, irrespective of cancer type. Geriatric assessment tests allow objective assessment of older patients with worst prognosis before treatment planning.
Unraveling Triple-Negative Breast Cancer Tumor Microenvironment Heterogeneity: Towards an Optimized Treatment Approach
Authors: Bareche Yacine , Buisseret Laurence , Gruosso Tina , Girard Edwina , Venet David , Dupont Floriane , Desmedt Christine , Larsimont Denis , Park Morag , Rothé Françoise , Stagg John , Sotiriou Christos
Published: October 2019

Background

Recent efforts of gene expression profiling analyses recognized at least four different triple-negative breast cancer (TNBC) molecular subtypes. However, little is known regarding their tumor microenvironment (TME) heterogeneity.

Methods

Here, we investigated TME heterogeneity within each TNBC molecular subtype, including immune infiltrate localization and composition together with expression of targetable immune pathways, using publicly available transcriptomic and genomic datasets from a large TNBC series totaling 1512 samples. Associations between molecular subtypes and specific features were assessed using logistic regression models. All statistical tests were two-sided.

Results

We demonstrated that each TNBC molecular subtype exhibits distinct TME profiles associated with specific immune, vascularization, stroma, and metabolism biological processes together with specific immune composition and localization. The immunomodulatory subtype was associated with the highest expression of adaptive immune-related gene signatures and a fully inflamed spatial pattern appearing to be the optimal candidate for immune check point inhibitors. In contrast, most mesenchymal stem-like and luminal androgen receptor tumors showed an immunosuppressive phenotype as witnessed by high expression levels of stromal signatures. Basal-like, luminal androgen receptor, and mesenchymal subtypes exhibited an immune cold phenotype associated with stromal and metabolism TME signatures and enriched in margin-restricted spatial pattern. Tumors with high chromosomal instability and copy number loss in the chromosome 5q and 15q regions, including genomic loss of major histocompatibility complex related genes, showed reduced cytotoxic activity as a plausible immune escape mechanism.

Conclusions

Our results demonstrate that each TNBC subtype is associated with specific TME profiles, setting the ground for a rationale tailoring of immunotherapy in TNBC patients.
The Social Context of Media Trust: A Network Influence Model
Authors: Ognyanova Katherine
Published: October 2019

Concerns about the low public trust in U.S. media institutions have recently deepened amid increasing partisan polarization, large-scale digital disinformation campaigns, and frequent attacks on the press from political elites. This study explored the social factors that shape our trust in mainstream news sources. An examination of longitudinal network data from 13 residential student communities highlighted the importance of interpersonal influence on views about the media. The results show that the media trust of participants was predicted by the trust scores of their online and offline social contacts. The most robust and consistent effect comes from face-to-face interactions with politically like-minded conversation partners. Among online social ties, the analysis found effects from contact with others who distrust the media, but not from communication with people who reported high levels of media trust.
RPK1 and BAK1 sequentially form complexes with OST1 to regulate ABA-induced stomatal closure
Authors: Shang Yun , Yang Dami , Ha Yunmi , Shin Hyun-young , Nam Kyoung Hee
Published: October 2019

Regulation of plant water status occurs via abscisic acid (ABA)-induced stomatal closure. Open Stomata 1 (OST1) is a critical ABA signaling component regulating this process in guard cells. We previously reported that BRI1-associated receptor kinase 1 (BAK1) positively regulates ABA-induced stomatal closure by interacting with, and phosphorylating OST1. Here, we show that the Receptor-like Protein Kinase 1 (RPK1), previously known to be induced by ABA, is a positive ABA-signaling component in guard cell movement, and interacts with OST1. ABA-inducible expression patterns were observed in RPK1 and OST1, but not in BAK1. We investigated the underlying mechanisms by which the RPK1/OST1 and BAK1/OST1 complexes interact in stomatal guard cells by monitoring the complex formation continuously using FRET analyses. We found that the BAK1/OST1 complex was formed earlier than the RPK1/OST1 complex in response to ABA. In vitro and semi-in vivo kinase assays revealed that a trans-phosphorylation event occurred in the RPK1/OST1 complex, which differs from that in the BAK1/OST1 complex, wherein only OST1 phosphorylation occurred via BAK1. ABA Insensitive 1 (ABI1) only dephosphorylated OST1 in the BAK1/OST1 complex, but dephosphorylated both RPK1 and OST1 proteins in the RPK1/OST1 complex. Our results suggest that there are multiple coordinated ABA signaling systems to regulate stomatal movement.
OsCYP71D8L as a key regulator involved in growth and stress response by mediating gibberellins homeostasis in rice
Authors: Zhou Jiahao , Li Zeyu , Xiao Guiqing , Zhai Mingjuan , Pan Xiaowu , Huang Rongfeng , Zhang Haiwen
Published: October 2019

Phytohormones are pivotal in the regulation of plant growth and development, and acclimation to adverse environments. Multiple cytochrome P450 monooxygenases (CYP450s) are involved in the biosynthesis and catabolism of phytohormones. Here, we reported that a CYP450 member of CYP71 clan, OsCYP71D8L, participated in the control of multiple agronomic traits and abiotic stress responses by affecting gibberellin (GA) and cytokinin (CK) homeostasis in rice. We found that its gain-of-function mutant (cyp71d8l) and transgenic plants overexpressing OsCYP71D8L (OsCYP71D8L-OE) displayed similar phenotypes including dwarfed plant, reduced panicle length and grain number per panicle, and their endogenous GAs levels were notably decreased as compared to wild type (WT), respectively. Moreover, the dwarfed plant and less developed root of OsCYP71D8L-OE and cyp71d8l seedlings could be rescued by exogenous GA3 and lovastatin, but exacerbated by exogenous 6-BA. Importantly, OsCYP71D8L-OE and cyp71d8l seedlings maintained high chlorophyll contents and low reactive oxygen species level, and showed the enhanced tolerance to drought and salt stress compared with WT. Thus, our results suggest that OsCYP71D8L plays important roles in regulating rice growth and stress responses by coordinating GAs and CKs homeostasis, and it is useful to engineer stress-tolerant rice.
Chinua Achebe’sThere was a Countryand the digital publics of African literature
Authors: Yeku James
Published: October 2019

A growing body of critical works on the digital expressions of African literature confirms the importance of digital literary studies in Africa. Examples of this growing scholarship include those of Shola Adenekan (2012) and Stephanie Santana (2018). Adenekan’s work focuses on ‘the Internetting of African literature’, while Santana's essay uses digital fiction from South Africa to offer a brilliant treatment of the connections between national spaces and digital networks. Several questions emerge, though, in considering how digital technologies reformulate the form, function, and audience of African literature. How are we, for instance, to understand the role of digital publics? What kind of ideological terrains emerge in online literary representations? What mediations do digital technologies bring to the changing forms and publics of contemporary writing in Africa? How does the ontology of the digital reconfigure the behaviour of the audience in the interpretation of literary meaning and how might previous scholarship such as those of Karin Barber’s on publics and audiences be read in the context of digitality? This article aims to answer these questions by examining some articulations of reader agency to Chinua Achebe’s There was a Country on digital avenues such as Facebook. Aside from an exploration of the intersection of digital culture and African literary forms, I hope to use online responses to Achebe’s memoir to track the trajectories of the new publics of African literature, showing how the ethnopolitics that greeted the publication of Achebe’s wartime narrative explicates the nature of digital publics
More Than Just Torsion: An Unusual Case of Testicular Pain
Authors: Martin Clyde Donald , Sulava Eric , Bloom Adam
Published: October 2019

Testicular pain has a wide differential and the nonspecific presentation should be triaged rapidly for urgent diagnosis and treatment. Scrotal pyoceles are uncommon collections of purulent fluid between the visceral and parietal tunica vaginalis, usually secondary to acute epididymo-orchitis, intra-abdominal infection, or trauma. Epididymitis and epididymo-orchitis are generally secondary to sexually transmitted infections or urinary tract pathogens. Epidymo-orchitis can compromise the testicular blood supply, leading to a microinfarction and rupture through the tunica albuginea; inflammatory and infectious material then translocate into the tunica vaginalis leading to the formation of a pyocele. Ultrasonography is the preferred method of diagnostic imaging, which can show a classic “falling snow” sign, loculations, or gas. The treatment for a scrotal pyocele is pain control, fluid resuscitation, broad-spectrum antibiotics, and early urology/general surgery consultation. In such cases, Fournier gangrene (FG) should be clinically ruled out and the presence of signs of Fournier gangrene should be met with an urgent surgical consult.
The histone variant H2A.Z in yeast is almost exclusively incorporated into the +1 nucleosome in the direction of transcription
Authors: Bagchi Dia N , Battenhouse Anna M , Park Daechan , Iyer Vishwanath R
Published: October 2019

Transcription start sites (TSS) in eukaryotes are characterized by a nucleosome-depleted region (NDR), which appears to be flanked upstream and downstream by strongly positioned nucleosomes incorporating the histone variant H2A.Z. H2A.Z associates with both active and repressed TSS and is important for priming genes for rapid transcriptional activation. However, the determinants of H2A.Z occupancy at specific nucleosomes and its relationship to transcription initiation remain unclear. To further elucidate the specificity of H2A.Z, we determined its genomic localization at single nucleosome resolution, as well as the localization of its chromatin remodelers Swr1 and Ino80. By analyzing H2A.Z occupancy in conjunction with RNA expression data that captures promoter-derived antisense initiation, we find that H2A.Z’s bimodal incorporation on either side of the NDR is not a general feature of TSS, but is specifically a marker for bidirectional transcription, such that the upstream flanking −1 H2A.Z-containing nucleosome is more appropriately considered as a +1 H2A.Z nucleosome for antisense transcription. The localization of H2A.Z almost exclusively at the +1 nucleosome suggests that a transcription-initiation dependent process could contribute to its specific incorporation.
Immune biology of glioma associated macrophages and microglia: Functional and therapeutic implications
Authors: Wei Jun , Chen Peiwen , Gupta Pravesh , Ott Martina , Zamler Daniel , Kassab Cynthia , Bhat Krishna P , Curran Michael A , de Groot John F , Heimberger Amy B
Published: October 2019

CNS immune defenses are marshalled and dominated by brain resident macrophages and microglia, which are the innate immune sentinels and frontline host immune barriers against various pathogenic insults. These myeloid lineage cells are the predominant immune population in gliomas, and can constitute up to 30–50% of the total cellular composition. Parenchymal microglial cells and recruited monocyte-derived macrophages from the periphery exhibit disease specific phenotypic characteristics with spatial and temporal distinctions and are heterogeneous subpopulations based on their molecular signatures. A preponderance of myeloid over lymphoid lineage cells during CNS inflammation, including gliomas, is a contrasting feature of brain immunity relative to peripheral immunity. Herein we discuss glioma associated macrophage and microglia immune biology in the context of their identity, molecular drivers of recruitment, nomenclature and functional paradoxes, therapeutic reprogramming and polarization strategies, relevant challenges, and our perspectives on therapeutic modulation.
Ultrasound Ablation in Neurosurgery: Current Clinical Applications and Future Perspectives
Authors: Franzini Andrea , Moosa Shayan , Prada Francesco , Elias W Jeffrey
Published: October 2019

The concept of focusing high-intensity ultrasound beams for the purpose of cerebral ablation has interested neurosurgeons for more than 70 yr. However, the need for a craniectomy or a cranial acoustic window hindered the clinical diffusion of this technique. Recent technological advances, including the development of phased-array transducers and magnetic resonance imaging technology, have rekindled the interest in ultrasound for ablative brain surgery and have led to the development of the transcranial magnetic resonance-guided focused ultrasound (MRgFUS) thermal ablation procedure. In the last decade, this method has become increasingly popular, and its clinical applications are broadening. Despite the demonstrated efficacy of MRgFUS, transcranial thermal ablation using ultrasound is limited in that it can target exclusively the central region of the brain where the multiple acoustic beams are most optimally focused. On the contrary, lesioning of the cortex, the superficial subcortical areas, and regions close to the skull base is not possible with the limited treatment envelope of current phased-array transducers. Therefore, new ultrasound ablative techniques, which are not based on thermal mechanisms, have been developed and tested in experimental settings. This review describes the mechanisms by which these novel, nonthermal ablative techniques are based and also presents the current clinical applications of MRgFUS thermal ablation.
Y-Stent-Assisted Coiling With Low-Profile Neuroform Atlas Stents for Endovascular Treatment of Wide-Necked Complex Intracranial Bifurcation Aneurysms
Authors: Aydin Kubilay , Balci Sinan , Sencer Serra , Barburoglu Mehmet , Umutlu Muzaffer Reha , Arat Anil
Published: October 2019

BACKGROUND

Y-stent-assisted coiling is one of the eligible techniques for the treatment of complex bifurcation aneurysms. In majority of previous literature, Y-stenting has been performed using stents that could be delivered through large profile microcatheters that are often difficult to manipulate during navigation through sharply angled side branches. Attempts to navigate with these large profile catheters might cause serious complications during Y-stenting procedure.

OBJECTIVE

To investigate the safety, feasibility, and efficacy of Y-stent-assisted coiling procedure with Neuroform Atlas stents for the treatment of complex bifurcation aneurysms; Neuroform Atlas is a recently introduced open-cell stent that can be delivered though low-profile microcatheters.

METHODS

We identified the patients with intracranial bifurcation aneurysms treated by Y-stent-assisted coiling procedure with Neuroform Atlas stents. We assessed the immediate postoperative and follow-up clinical and angiographic outcomes. We also investigated the periprocedural and delayed complications.

RESULTS

A total of 30 aneurysms in 30 patients were included in the study. Y-stenting was successfully performed without any technical complications in all cases (100%). Immediate postprocedural angiography revealed total aneurysm occlusion in 83.3% of patients. The mean angiographic follow-up time was 11.8 mo. The last follow-ups showed complete occlusion in 93.3% of patients. There was no mortality in this study. A procedure-related complication developed in 6.7% and resulted in permanent morbidity in 3.3% of patients.

CONCLUSION

Neuroform Atlas stent combines the advantages of low-profile deployment microcatheters with an open-cell structure to achieve a successful Y-stenting procedure. Y-stent-assisted coiling with Neuroform Atlas stents provides a safe and effective endovascular treatment for wide-necked complex bifurcation aneurysms.
Bishops, 1550–1700
Authors: Fletcher Stella
Published: October 2019

The church “thinks in centuries,” meaning that the role and significance of the episcopate remained the same in the period from 1550 to 1700 as it had in the time period covered in Oxford Bibliographies in Renaissance and Reformation article “Bishops, 1400–1550.”The same Reference Works can be consulted for both the earlier and the later period, though for the purposes of the current article they are subdivided between those of a General nature, spanning the whole of Catholic Christendom, and those with a Geographically Specific remit. Similarly, Journals specializing in ecclesiastical history publish articles about bishops of any and every century. When one turns to Overviews and Collections of Papers relating specifically to episcopacy in the early modern period, it becomes apparent that bishops have been historiographically unfashionable, for there are noticeably fewer publications relating to this period than there are for 1400–1550. Even though Lutheran and Calvinist reformers rejected episcopacy to varying degrees, the ecclesiastical geography of Europe changed little. In Germany the tradition of prince-bishops was so strong that some princes turned Lutheran but retained their episcopal titles, while the succession of Catholic bishops continued without any such confusion. In Scandinavia and the British Isles, that succession was simultaneously broken and maintained: bishops ceased to be appointed through a combination of secular and papal patronage but were retained because they were useful to the secular authorities; a hybrid of Protestantism and episcopacy was created, Lutheran or Anglican bishops sitting on the thrones of their Catholic predecessors. All the while, the bishoprics of southeastern Europe remained in the hands of the Ottoman Turks, but new dioceses were being created in Asia and the Americas. Confessional divisions and the diminished significance of bishops are reflected in the fact that Germany and the Low Countries are grouped together in this article. European Christendom’s retreat westward is apparent in the section devoted to Italy and the Eastern Mediterranean, in which Venetian bishops dominate. Much of Italy was ruled by Spanish kings and their viceroys, so Spain and Its Empire is treated next. From 1581 to 1640 the Spanish monarchs also ruled Portugal and Its Empire. Europe’s political center of gravity moved toward France, which not only incorporated bishoprics that had previously been outside its borders, but has also been the subject of the most important studies of early modern bishops. The shift toward the Atlantic is completed in the British Isles, where confessional divisions account for subsections on Catholics and Anglicans. In all these sections, no separation is made between primary and secondary sources. To conclude, diverse parts of Europe are united in Bishops in Early Modern Culture.
From "National Culture" to the "National Popular" and the Andean Novel (1889-1950)
Authors: Sanjinés C. Javier
Published: October 2019

Given the ideological relationship between literature—as practice and as discipline—and the organization of the Spanish-American nation states, it is surprising that—with notable exceptions—literary criticism dedicated to the study of Peru, Ecuador, and Bolivia, did not place sufficient emphasis on the conflict around the construction of the “national culture” and the conflicts created by the “national-popular.” The concept of “national culture” is close to the idea of the “civic” nation, and the “national-popular,” a modernizing proposal, seeks to move beyond the national culture proposed by the criollo elites of the first two decades of the 20th century. Thus, the “national-popular” is of a different political-ideological cast: the drive to create a national democratic subject that was no longer able to continue circulating smoothly within the bourgeois liberal discourse that produced the “national culture.”
Children, Young People, and Architecture
Authors: Parnell Rosie , Patsarika Maria
Published: October 2019

Defining the scope of children, young people, and architecture as a field is an interesting challenge, since architecture draws on the theories and knowledge of a wide range of disciplines to inform its own understandings. Scale also comes into question: architecture can be understood to be strategic as well as haptic; sociocultural and political as well as experiential and material. This article focuses primarily on architecture as design and social process, with a spatial product. Work in this field, as delimited, can be grouped into five areas: children’s spaces as product, the impact of built environment on children, design participation process, appropriation of space, and children’s architectural education. However, architecture as a discipline has not yet created a substantial scholarly body of work on any topic within this field, except perhaps for school design. Work related to children, young people, and architecture exists within Oxford Bibliographies at the scale of the city, neighborhood, and landscape—including school grounds (see the separate Oxford Bibliographies articles in Childhood Studies “Children and the Environment”; “Children’s Geographies”; “Geographies of Children and Childhood”; and “The Spaces of Childhood”. A selection of work addressing the city scale is included here as a context essential to the critical development and understanding of the spatial designer and architectural researcher. The work of historians—primarily centering on schools—is followed by sources that provide An Overview of Children’s Spaces, before moving on to specific Typologies of Space (see also the separate Oxford Bibliographies article in Childhood Studies “Children’s Museums”. The Participation in the Design Process section broadly considers spatial design process with children, where researcher-practitioners from a range of disciplines have made significant contributions. The Impact of the Built Environment on children as occupiers, or “users,” is considered in two separate realms: Health and Well-Being and Academic Performance and Student Behavior. Since the process of creating architecture is here understood to continue beyond design, into inhabitation, children’s creation of space through Appropriation of Space is given separate attention. Finally, the growing subfield of Children’s Architecture Education—or, more broadly, built environment education—is scoped through the few scholarly articles and book chapters that have emerged in recent years. In summary, this is a young field, as reflected in the lack of textbooks, anthologies, and journals dedicated specifically to children, young people, and architecture. There is great potential for architecture, including its design- and practice-based research methods, to make further contributions to understandings of childhood and its relationship to space.
Pacific Lithosphere Evolution Inferred from Aitutaki Mantle Xenoliths
Authors: Snortum Eric , Day James M D , Jackson Matthew G
Published: October 2019

Highly siderophile element (HSE: Os, Ir, Ru, Pt, Pd, Re), major and trace element abundances, and 187Re–187Os systematics are reported for xenoliths and lavas from Aitutaki (Cook Islands), to investigate the composition of Pacific lithosphere. The xenolith suite comprises spinel-bearing lherzolites, dunite, and harzburgite, along with olivine websterite and pyroxenite. The xenoliths are hosted within nephelinite and alkali basalt volcanic rocks (187Os/188Os ∼0·1363 ± 13; 2SD; ΣHSE = 3–4 ppb). The volcanic host rocks are low-degree (2–5%) partial melts from the garnet stability field and an enriched mantle (EM) source. Pyroxenites have similar HSE abundances and Os isotope compositions (Al2O3 = 5·7–8·3 wt %; ΣHSE = 2–4 ppb; 187Os/187Os = 0·1263–0·1469) to the lavas. The pyroxenite and olivine websterite xenoliths directly formed from—or experienced extensive melt–rock interaction with—melts similar in composition to the volcanic rocks that host the xenoliths. Conversely, the Aitutaki lherzolites, harzburgites and dunites are similar in composition to abyssal peridotites with respect to their 187Os/188Os ratios (0·1264 ± 82), total HSE abundances (ΣHSE = 8–28 ppb) and major element abundances, forsterite contents (Fo89·9±1·2), and estimated extents of melt depletion (<10 to >15%). These peridotites are interpreted to sample relatively shallow Pacific mantle lithosphere that experienced limited melt–rock reaction and melting during ridge processes at ∼90 Ma. A survey of maximum time of rhenium depletion ages of Pacific mantle lithosphere from the Cook (Aitutaki ∼1·5 Ga), Austral (Tubuai’i ∼1·8 Ga), Samoan (Savai’i ∼1·5 Ga) and Hawaiian (Oa’hu ∼2 Ga) island groups shows that Mesoproterozoic to Neoproterozoic depletion ages are preserved in the xenolith suites. The variable timing and extent of mantle depletion preserved by the peridotites is, in some instances, superimposed by extensive and recent melt depletion as well as melt refertilization. Collectively, Pacific Ocean island mantle xenolith suites have similar distributions and variations of 187Os/188Os and HSE abundances to global abyssal peridotites. These observations indicate that Pacific mantle lithosphere is typical of oceanic lithosphere in general, and that this lithosphere is composed of peridotites that have experienced both recent melt depletion at ridges and prior and sometimes extensive melt depletion across several Wilson cycles spanning periods in excess of two billion years.
Fracture prevention: a population-based intervention delivered in primary care
Authors: Hoggard K , Hart S , Birchall J , Kirk S , Goff I , Grove M , Newton J
Published: October 2019

Background

Osteoporosis is common, increasing as the population ages and has significant consequences including fracture. Effective treatments are available.

Aim

To support proactive fracture risk assessment (FRAX) and optimizing treatment for high-risk patients in primary care.

Design

Clinical cohort

Setting

November 2017 to November 2018, support was provided to 71 practices comprising 69 of 90 practices within two National Health Service Clinical Commissioning Groups areas. Total population 579 508 (207 263 aged over 50 years).

Participants

FRAX (National Institute for Care and Clinical Excellence, NICE CG146) in (i) males aged 75 years and over, (ii) females aged 65 years and over, (iii) females aged under 65 years and males aged under 75 years with risk factors and (iv) under 50 years with major risk factors.

Results

A total of 158 946 met NICE CG146, 11 961 were coded with an osteoporosis diagnosis (7.5%), of those, 42% were prescribed treatment with a bone sparing agent (BSA). In total, 6942 were assessed to initiate BSA. Thirty percent of untreated osteoporosis diagnosis patients had never been prescribed BSA. Even when prescribed, 1700 people (35%) were for less than minimum recommended duration. Of the total 9784 patients within the FRAX recommended to treat threshold, 3197 (33%) were currently treated with BSA and 3684 (37%) had no history of ever receiving BSA. From untreated patients, expected incidence of 875 fractures over a 3-year period (approximately £3.4 million). Treatment would prevent 274 fractures (cost reduction: £1 274 045, with prescribing costs: saving £805 145 after 3 years of treatment).

Conclusion

Underdiagnosis and suboptimal treatment of osteoporosis was identified. Results suggest that implementing NICE guidance and optimizing treatment options in practice is possible and could prevent significant fractures.
IgA vasculitis and anti-GBM disease: two ends of a spectrum of immune complex vasculitis
Authors: Salama Alan D
Published: October 2019

Two immune complex vasculitides, IgA vasculitis (IgAV) and anti-GBM disease, represent polar extremes with regard to our understanding of disease pathogenesis, standardized management protocols and outcomes. This report compares our current approach to these uncommon entities in adults. Both diseases demonstrate degrees of small vessel necrosis and glomerular crescent formation. IgAV has an antibody response directed against unknown antigens, is often treated conservatively and has poorly studied long term renal outcomes. By contrast, anti-GBM disease presents with rapidly progressive glomerulonephritis and often results in end stage renal failure, despite intensive immunosuppression. Rarely, some cases of anti-GBM disease may be IgA predominant and bind other α-chains present in the GBM, but their clinical course is as for other anti-GBM disease patients but not IgAV, suggesting that the antigenic target rather than the antibody subclass is the critical factor in determining disease outcome. However, both conditions are associated with increased mortality in adults and result in significant chronic kidney disease and hypertension.