bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of incidence and geographical distribution of Chagas disease in Mexico during a decade (2007–2016)
Authors: Ibáñez-Cervantes G. , León-García G. , Castro-Escarpulli G. , Mancilla-Ramírez J. , Victoria-Acosta G. , Cureño-Díaz M.A. , Sosa-Hernández O. , Bello-López J.M.
Published: November 2018

Chagas disease, whose aetiological agent is the protozoanTrypanosoma cruzi, mainly occurs in Latin America. In order to know the epidemiology and the geographical distribution of this disease in Mexico, the present work analyses the national surveillance data (10 years) for Chagas disease issued by the General Directorate of Epidemiology (GDE). An ecological analysis of Chagas disease (2007–2016) was performed in the annual reports issued by the GDE in Mexico. The cases and incidence were classified by year, state, age group, gender and seasons. A national distribution map showing Chagas disease incidence was generated. An increase of new cases was identified throughout the country (rates from 0.37 to 0.81 per 100 000 inhabitants). Of the total cases accumulated (7388), the major cases were attributed to the states of Veracruz, Chiapas, Quintana Roo, Oaxaca, Morelos and Yucatán. The analysis per age groups and gender revealed that, in most age groups, the incidence was higher in the male population. The most number of cases was identified in spring and summer; a direct relationship between the environmental temperature increase and the number of new cases was identified. The analysis showed that the rate of Chagas disease increased presumably due to state programmes; the search for new cases has expanded and we speculate that the disease is associated with occupational activities. These results summarise and recall how important it is to implement the monitoring of Chagas disease mainly in south states of the Mexican Republic in order to implement strategies to control this disease.
Does rescue in vitro maturation of germinal vesicle stage oocytes impair embryo morphokinetics development?
Authors: Faramarzi Azita , Khalili Mohammad Ali , Ashourzadeh Sareh , Palmerini Maria Grazia
Published: November 2018

Currently, rescue in vitro maturation (IVM) is not a routine method in assisted reproductive treatment (ART) programmes but is a promising procedure for ART to improve IVM. The aim of this study was to compare embryo morphokinetics of germinal vesicles (GV) with metaphase II (MII) oocytes from controlled ovarian hyperstimulation (COH) cycles by time-lapse photography monitoring (TLM). Morphokinetics of the same number of embryos derived from the in vivo (group I) and rescue of in vitro matured oocytes (group II) from 310 patients were analyzed and compared retrospectively. The time to form second PB extrusion (tPB2), time of pronuclei appearance (tPNa), time of pronuclei fading (tPNf) and time of two to eight discrete cells (t2–t8) were assessed. Abnormal cleavage patterns such as uneven blastomeres at the two-cell stage, cell fusion (Fu), trichotomous mitoses (TM), and the rates of embryo arrest were assessed. These data showed that tPB2, tPNa, tPNf, t2, t3 and t4 stages took place later in group II compared with group I (P<0.001, P=0.017, P<0.001, P<0.001, P<0.001, P<0.001, respectively). The rates of uneven blastomeres, Fu, TM, and embryo arrest were increased significantly in group II compared with group I (P=0.001, P<0.001, P=0.003, P<0.001, respectively). Based on the exact annotation of timing parameters and cleavage patterns, the present data agreed with the concept that rescue IVM of oocytes negatively influences embryo morphokinetics. Therefore, cautious use of embryos derived from rescue IVM of GV oocytes should be made.
Safety, Tolerability, and Efficacy of Desvenlafaxine in Children and Adolescents with Major Depressive Disorder: Results from Two Open-Label Extension Trials
Authors: Atkinson Sarah , Thurman Louise , Ramaker Sara , Buckley Gina , Jones Sarah Ruta , England Richard , Wajsbrot Dalia
Published: November 2018

Objective

Two similarly designed extension studies evaluated the long-term safety and tolerability of desvenlafaxine for the treatment of children and adolescents with major depressive disorder (MDD). Efficacy was evaluated as a secondary objective.

Methods

Both 6-month, open-label, flexible-dose extension studies enrolled children and adolescents who had completed one of two double-blind, placebo-controlled, lead-in studies. One lead-in study included a 1-week transition period prior to the extension study. Patients received 26-week treatment with flexible-dose desvenlafaxine (20–50 mg/d). Safety assessments included comprehensive psychiatric evaluations, vital sign assessments, laboratory evaluations, 12-lead electrocardiogram, physical examination with Tanner assessment, and Columbia-Suicide Severity Rating Scale. Adverse events (AEs) were collected throughout the studies. Efficacy was assessed using the Children’s Depression Rating Scale–Revised (CDRS-R).

Results

A total of 552 patients enrolled (completion rates: 66.4 and 69.1%). AEs were reported by 79.4 and 79.1% of patients in the two studies; 8.9 and 5.2% discontinued due to AEs. Treatment-emergent suicidal ideation or behavior was reported for 16.6 and 14.1% of patients in the two studies. Mean (SD) CDRS-R total score decreased from 33.83 (11.93) and 30.92 (10.20) at the extension study baseline to 24.31 (7.48) and 24.92 (8.45), respectively, at week 26.

Conclusion

Desvenlafaxine 20 to 50 mg/d was generally safe and well tolerated with no new safety signals identified in children and adolescents with MDD who received up to 6 months of treatment in these studies. Patients maintained the reduction in severity of depressive symptoms observed in all treatment groups at the end of the lead-in study.
Caring for Esteem and Intellectual Reputation: Some Epistemic Benefits and Harms
Authors: Tanesini Alessandra
Published: November 2018

This paper has five aims: it clarifies the nature of esteem and of the related notions of admiration and reputation (sect. 1); it argues that communities that possess practices of esteeming individuals for their intellectual qualities are epistemically superior to otherwise identical communities lacking this practice (sect. 2) and that a concern for one's own intellectual reputation, and a motivation to seek the esteem and admiration of other members of one's community, can be epistemically virtuous (sect. 3); it explains two vices regarding these concerns for one's own intellectual reputation and desire for esteem: intellectual vanity and intellectual timidity (sect. 4); finally (sect. 5), it offers an account of some of the epistemic harms caused by these vices.
Understanding Epistemic Trust Injustices and Their Harms
Authors: Grasswick Heidi
Published: November 2018

Much of the literature concerning epistemic injustice has focused on the variety of harms done to socially marginalized persons in their capacities as potentialcontributorsto knowledge projects. However, in order to understand the full implications of the social nature of knowing, we must confront the circulation of knowledge and the capacity of epistemic agents to take up knowledge produced by others and make use of it. I argue that members of socially marginalized lay communities can sufferepistemic trust injusticeswhen potentially powerful forms of knowing such as scientific understandings are generated in isolation from them, and when the social conditions required for aresponsibly-placed trustto be formed relative to the relevant epistemic institutions fail to transpire.
Phrasal compounds can have adjectival heads: evidence from English
Authors: GÜNTHER CHRISTINE , KOTOWSKI SVEN , PLAG INGO
Published: November 2018

Phrasal compounds are taken to be word-level structures that combine a lexical head with a phrasal non-head. Several claims have emerged from the pertinent literature: phrasal compounds allegedly only have nominal heads, can host a variety of syntactic structures in non-head position, are determinative, and are instances of expressive morphology. The existence of adjectival phrasal compounds is either explicitly denied in the literature, or considered a marginal phenomenon at best. This article presents data from theCorpus of Contemporary American English(COCA; Davies 2008) that show that adjectival phrasal compounds do exist in English. We demonstrate that they are similar to non-phrasal adjectival compounds and to nominal phrasal compounds. At the same time, they crucially differ from nominal compounds in the prototypical semantic relations between head and non-head: adjectival phrasal compounds are mostly similative-intensifying as opposed to determinative. We argue that this property is also found in noun–adjective compounds and follows naturally from the semantics of the head category in question, viz. adjectives as mostly gradable predicates. In turn, the majority of adjectival phrasal compounds in our data feature a strong expressive component, a characteristic they share with other phrasal compounds.
WRESTLING WITH THE SHADOW: THE PANLOGISM CONTROVERSY IN HEGEL'S FRENCH RECEPTION (1897–1927)
Authors: TERZI PIETRO
Published: November 2018

This article widens the scope of the history of Hegel's reception in turn-of-the-century French philosophy by thematizing an often neglected moment, namely the years 1897 to 1927. Before the so-called “Hegel renaissance,” in fact, the Hegelian dialectics was generally understood as a “panlogist” doctrine aimed at dissolving the concrete individual in the abstract dimension of the concept or in the all-encompassing realm of Absolute Spirit. However, even at the beginning of the century, attempts were made to provide a more positive assessment of Hegelian philosophy. The author reconstructs this panlogist controversy by analyzing the points of view of some prominent philosophers of the time, namely Charles Renouvier, René Berthelot, Émile Boutroux, Émile Meyerson and Léon Brunschvicg. The aim of the article is to provide a deeper understanding of the historical continuities and discontinuities characterizing Hegel's reception in France.
Persistent organic pollutants (PAH, PCB, TPH) in freshwater, urban tributary and estuarine surface sediments of the River Clyde, Scotland, UK
Authors: Vane Christopher H. , Lopes dos Santos Raquel A. , Kim Alexander W. , Moss-Hayes Vicky , Fordyce Fiona M. , Bearcock Jenny M.
Published: November 2018

Surface sediments from a 160-km stretch of the River Clyde, Scotland, were analysed for persistent organic pollutants to investigate distribution, source and environmental effect. Glasgow's urban tributaries polyaromatic hydrocarbons (PAH) ranged from 2.3 to 4226mgkg–1, total petroleum hydrocarbons (TPH) 72 to 37879mgkg–1 and polychlorinated biphenyls (PCB) 3 to 809μgkg–1, which were more polluted than the upper River Clyde PAH that ranged from 0.1 to 42mgkg–1, TPH 3 to 260mgkg–1 and PCB 2 to 147μgkg–1. Intermediate values of the inner Clyde estuary PAH ranging from 0.6 to 30mgkg–1, and PCB ranging from 5 to 130μgkg–1, were attributed to point sources and sediment transfer from the urban tributaries. Comparison with sediment quality criteria suggested possible adverse effects on aquatic biota. PAH isomeric ratios confirmed a pyrolytic source throughout the Clyde and benzo[a]pyrene/benzo[g,h,i]perylene ratios >0.6 confirmed that upper, urban and estuarine domains all to a lesser or greater extent accumulated PAH from traffic emissions. The degree of chlorination determined from PCB homologues differed in each of the three domains, suggesting variable source or that the process aerobic/anaerobic degradation varied in each of the three domains. The anthropogenic impact of the city of Glasgow can be quantified in that the urban tributary sediment mean values were 60 (PAH), 33 (TPH) and 11 (PCB) times higher than the rural upper Clyde counterpart.
Polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) in urban soils of Glasgow, UK
Authors: Kim Alexander W. , Vane Christopher H. , Moss-Hayes Vicky L. , Beriro Darren J. , Nathanail C. Paul , Fordyce Fiona M. , Everett Paul A.
Published: November 2018

Concentrations of total organic carbon (TOC), total petroleum hydrocarbons, polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) were determined in 84 near-surface soils (5–20cm depth) taken from a 255km2 area of Glasgow in the Clyde Basin, UK, during July 2011. Total petroleum hydrocarbon range was 79–2,505mgkg–1 (mean 388mgkg–1; median 272mgkg–1) of which the aromatic fraction was 13–74 % (mean 44 %, median 43 %) and saturates were 28–87 % (mean 56 %, median 57 %). ∑16 PAH varied from 2–653mgkg–1 (mean 32.4mgkg–1; median 12.5mgkg–1) and ∑31 PAH range was 2.47–852mgkg–1 (mean 45.4mgkg–1; median 19.0mgkg–1). ∑PCBtri-hepta range was 2.2–1052μgkg–1 (mean 32.4μgkg–1; median 12.7μgkg–1) and the ∑PCB7 range was 0.3–344μgkg–1 (mean 9.8μgkg–1; median 2.7μgkg–1). The concentration, distribution and source of the persistent organic pollutants were compared with those found in urban soils from other cities and to human health assessment criteria for chronic exposure to chemicals in soil. Total concentrations encountered were generally similar to other urban areas that had a similar industrial history. Benzo[a]pyrene concentrations were assessed against four different land use scenarios (irrespective of current land use) using generic assessment criteria resulting in six of 84 samples exceeding the residential criteria. Isomeric PAH ratios and relative abundance of perylene suggest multiple and environmentally modified pyrogenic PAH sources, inferred to be representative of diffuse pollution. ∑PCB7 concentrations were exceeded in 10 % of sites using the Dutch target value of 20μgkg–1. PCB congener profiles were environmentally attenuated and generally dominated by penta-, hexa- and hepta-chlorinated congeners.
Linkage between solid-phase apportionment and bioaccessible arsenic, chromium and lead in soil from Glasgow, Scotland, UK
Authors: Wragg Joanna , Broadway Andrew , Cave Mark R. , Fordyce Fiona M. , Palumbo-Roe Barbara , Beriro Darren J. , Farmer John G. , Graham Margaret C. , Ngwenya Bryne T. , Bewley Richard J. F.
Published: November 2018

The chemical composition of soil from the Glasgow (UK) urban area was used to identify the controls on the availability of potentially harmful elements (PHEs) in soil to humans. Total and bioaccessible concentrations of arsenic (As), chromium (Cr) and lead (Pb) in 27 soil samples, collected from different land uses, were coupled to information on their solid-phase partitioning derived from sequential extraction data. The total element concentrations in the soils were in the range <0.1–135mgkg–1 for As; 65–3680mgkg–1 for Cr and 126–2160mgkg–1 for Pb, with bioaccessible concentrations averaging 27, 5 and 27% of the total values, respectively. Land use does not appear to be a predictor of contamination; however, the history of the contamination is critically important. The Chemometric Identification of Substrates and Element Distribution (CISED) sequential chemical extraction and associated self-modelling mixture resolution analysis identified three sample groupings and 16 geochemically distinct phases (substrates). These were related to iron (n=3), aluminium–silicon (Al–Si; n=2), calcium (n=3), phosphorus (n=1), magnesium (Mg; n=3), manganese (n=1) and easily extractable (n=3), which was predominantly made up of sodium and sulphur. As, Cr and Pb were respectively found in 9, 10 and 12 of the identified phases, with bioaccessible As predominantly associated with easily extractable phases, bioaccessible Cr with the Mg-dominated phases and bioaccessible Pb with both the Mg-dominated and Al–Si phases. Using a combination of the Unified Barge Method to measure the bioaccessibility of PHEs and CISED to identify the geochemical sources has allowed a much better understanding of the complexity of PHE mobility in the Glasgow urban environment. This approach can be applied to other urban environments and cases of soil contamination, and made part of land-use planning.
Impact of economic crises on mental health care: a systematic review
Authors: Silva M. , Resurrección D. M. , Antunes A. , Frasquilho D. , Cardoso G.
Published: November 2018

Aims

Unmet needs for mental health treatment are large and widespread, and periods of economic crisis may increase the need for care and the treatment gap, with serious consequences for individuals and society. The aim of this systematic review was to summarise the empirical evidence on the association between periods of economic crisis and the use of mental health care.

Methods

Following the PRISMA statement, MEDLINE, Embase, Scopus, Open Grey and Cochrane Database were searched for relevant publications, published between 1990 and 2018, from inception to June 2018. Search terms included (1) economic crisis, (2) use of mental health services and (3) mental health problems. Study selection, data extraction and the assessment of study quality were performed in duplicate.

Results

Seventeen studies from different countries met the inclusion criteria. The results from the included articles suggest that periods of economic crisis might be linked to an increase of general help sought for mental health problems, with conflicting results regarding the changes in the use of specialised psychiatric care. The evidence on the use of mental health care specifically due to suicide behaviour is mixed. The results also suggest that economic crises might be associated with a higher use of prescription drugs and an increase in hospital admissions for mental disorders.

Conclusions

Research on the impact of economic crises on the use of mental health care is scarce, and methodologies of the included papers are prone to substantial bias. More empirical and long-term studies on this topic are needed, in order to adapt mental health care systems to the specific needs of the population in times of economic crisis.
Is the future of agriculture perennial? Imperatives and opportunities to reinvent agriculture by shifting from annual monocultures to perennial polycultures
Authors: Crews Timothy E. , Carton Wim , Olsson Lennart
Published: November 2018

Non-technical summary

Modern agriculture is associated with numerous environmental predicaments, such as land degradation, water pollution, and greenhouse gas emission. Socio-economically, it is characterized by a treadmill of technological change, increased mechanization, and economic consolidation, while depressing economic returns to farmers. A root cause is the dominance of annual plants cultivated in monocultures. Annual crops require the yearly clearing of vegetation resulting in soil erosion and other forms of ecosystem degradation. Monocultures are susceptible to agricultural pests and weeds. By contrast, perennial polycultures informed by natural ecosystems, promise more sustainable agroecosystems with the potential to also revitalize the economic foundation of farming and hence rural societies.
Cultivation and Reduced-Rate Herbicides Weed Control in Sugarbeet Grown for Biofuel
Authors: Johnson W. Carroll , Webster Theodore M. , Grey Timothy L. , Luo Xuelin
Published: November 2018

Sugarbeet, grown for biofuel, is being considered as an alternate cool-season crop in the southeastern United States. Previous research identified ethofumesate PRE and phenmedipham + desmedipham POST as herbicides that controlled troublesome cool-season weeds in the region, specifically cutleaf evening-primrose. Research trials were conducted from 2014 through 2016 to evaluate an integrated system of sweep cultivation and reduced rates of ethofumesate PRE and/or phenmedipham+desmedipham POST for weed control in sugarbeet grown for biofuel. There were no interactions between the main effects of cultivation and herbicides for control of cutleaf evening-primrose and other cool-season species in two out of three years. Cultivation improved control of cool-season weeds, but the effect was largely independent of control provided by herbicides. Of the herbicide combinations evaluated, the best overall cool-season weed control was from systems that included either a 1/2X or 1X rate of phenmedipham+desmedipham POST. Either rate of ethofumesate PRE was less effective than phenmedipham+desmedipham POST. Despite improved cool-season weed control, sugarbeet yield was not affected by cultivation each year of the study. Sugarbeet yields were greater when treated with any herbicide combination that included either a 1/2X or 1X rate of phenmedipham+desmedipham POST compared with either rate of ethofumesate PRE alone or the nontreated control. These results indicate that cultivation has a very limited role in sugarbeet grown for biofuel. The premise of effective weed control based on an integration of cultivation and reduced herbicide rates does not appear to be viable for sugarbeet grown for biofuel.
Polypharmazie in der Anwendung von Psychopharmaka in der deutschen Kinder- und Jugendpsychiatrie – häufiger Regel als Ausnahme
Authors: Vloet Timo D. , Egberts Karin , Taurines Regina , Wewetzer Christoph , Mehler-Wex Claudia , Plener Paul L. , Romanos Marcel , Gerlach Manfred
Published: November 2018

Zusammenfassung. Hintergrund: Die gleichzeitige Einnahme verschiedener Arzneimittel erhöht die Wahrscheinlichkeit von Wechselwirkungen und unerwünschten Arzneimittelwirkungen (UAWs). In der Kinder- und Jugendpsychiatrie wird versucht, Polypharmazie zu vermeiden, wobei allerdings kaum Daten zur Häufigkeit vorliegen. Ziel der Studie war die Untersuchung der Häufigkeit von Polypharmazie bei der Behandlung mit verschiedenen Antidepressiva und Antipsychotika sowie der fraglichen Assoziation mit einem erhöhten Auftreten von UAWs im Vergleich zur Monotherapie. Methodik: 940 Datensätze von Kindern und Jugendlichen unter Psychopharmakotherapie aus 10 Studien zum Therapeutischen Drug Monitoring (TDM) in Deutschland wurden retrospektiv-deskriptiv ausgewertet. Ergebnis: Polypharmazie war in bis zu 72.1 % der Fälle bei primärer Therapie mit Olanzapin und in bis zu 45.6 % der Fälle bei Escitalopram zu beobachten. In bis zu 17.4 % der Fälle wurden vier und mehr Neuro-/Psychopharmaka gleichzeitig eingesetzt. Bei Antipsychotika wurde keine erhöhte Häufigkeit von UAWs unter Polypharmazie dokumentiert. Bei den Antidepressiva wurden bei Sertralin signifikant mehr UAWs unter Polypharmazie beobachtet. Diskussion und Fazit: Polypharmazie wird relativ häufig angewandt. Rückschlüsse zum UAW-Risiko sollten aufgrund der geringen Fallgröße der untersuchten Subpopulationen, der Limitationen naturalistischer Studien sowie möglicher Doppelauswertungen unter Vorbehalt gezogen werden. Weiterführende Studien mit größeren und im Hinblick auf z. B. Alter und komorbide Störungen homogeneren Gruppen sind notwendig.
Wada Receives 2018 Hydrologic Sciences Early Career Award
Authors:   AGU
Published: November 2018

Yoshihide Wada will receive the 2018 Hydrologic Sciences Early Career Award at AGU’s Fall Meeting 2018, to be held 10–14 December in Washington, D. C. The award “acknowledges early career prominence and promise of continued contributions to hydrologic science.”
Why Is the Gulf of Maine Warming Faster Than 99% of the Ocean?
Authors: Poppick Laura
Published: November 2018

The Gulf of Maine’s location at the meeting point of two major currents, as well as its shallow depth and shape, makes it especially susceptible to warming.
Earthquake Catalog‐Based Machine Learning Identification of Laboratory Fault States and the Effects of Magnitude of Completeness
Authors: Lubbers Nicholas , Bolton David C. , Mohd‐Yusof Jamaludin , Marone Chris , Barros Kipton , Johnson Paul A.
Published: November 2018

Machine learning regression can predict macroscopic fault properties such as shear stress, friction, and time to failure using continuous records of fault zone acoustic emissions. Here we show that a similar approach is successful using event catalogs derived from the continuous data. Our methods are applicable to catalogs of arbitrary scale and magnitude of completeness. We investigate how machine learning regression from an event catalog of laboratory earthquakes performs as a function of the catalog magnitude of completeness. We find that strong model performance requires a sufficiently low magnitude of completeness, and below this magnitude of completeness, model performance saturates.
Evaluation of a MetOp ASCAT‐Derived Surface Soil Moisture Product in Tundra Environments
Authors: Högström Elin , Heim Birgit , Bartsch Annett , Bergstedt Helena , Pointner Georg
Published: November 2018

Satellite‐derived surface soil moisture data are available for the Arctic, but detailed validation is still lacking. Previous studies have shown low correlations between in situ and modeled data. It is hypothesized that soil temperature variations after soil thaw impact MetOp ASCAT satellite‐derived surface soil moisture (SSM) measurements in wet tundra environments, as C band backscatter is sensitive to changes in dielectric properties. We compare in situ measurements of water content within the active layer at four sites across the Arctic in Alaska (Barrow, Sagwon, Toolik) and Siberia (Tiksi), taken in the spring after thawing and in autumn prior to freezing. In addition to the long‐term measurement fields, where sensors are installed deeper in the ground, we designed a monitoring setup for measuring moisture very close to the surface in the Lena River Delta, Siberia. The volumetric water content (VWC) and soil temperature sensors were placed in the moss organic layer in order to account for the limited penetration depth of the radar signal. ASCAT SSM variations are generally very small, in line with the low variability of in situ VWC. Short‐term changes after complete thawing of the upper organic layer, however, seem to be mostly influenced by soil temperature. Correlations between SSM and in situ VWC are generally very low, or even negative. Mean standard deviation matching results in a comparably high root‐mean‐square error (on average 11%) for predictions of VWC. Further investigations and measurement networks are needed to clarify factors causing temporal variation of C band backscatter in tundra regions.
TGFβ1 signaling sustains aryl hydrocarbon receptor (AHR) expression and restrains the pathogenic potential of TH17 cells by an AHR-independent mechanism
Authors: de Lima Kalil Alves , Donate Paula Barbim , Talbot Jhimmy , Davoli-Ferreira Marcela , Peres Raphael Sanches , Cunha Thiago Mattar , Alves-Filho José Carlos , Cunha Fernando Queiroz
Published: November 2018

The aryl hydrocarbon receptor (AHR) is a transcription factor activated by ligand highly expressed on TH17 cells, and AHR-deficient CD4+ T cells have impaired production of IL-17A and IL-22. Although AHR activation can exacerbate in vivo TH17 cell-mediated autoimmunity, accumulating data indicate that AHR is a nonpathogenic TH17 marker. Thus it remains unclear how AHR activation is regulated and impacts on the generation of TH17 subsets. Here we demonstrated that AHR pathway is activated during in vitro pathogenic TH17 polarization, but it is quickly downregulated. Under these conditions, additional AHR activation promoted IL-22 but not IL-17A. Interestingly, AHR high sustained expression and IL-17A promotion were only achieved when TGFβ1 was present in the culture. In addition to the effect on AHR regulation, TGFβ1 presented a dual role by simultaneously suppressing the TH17 pathogenic phenotype acquisition. This latter effect was independent of AHR stimulation, since its activation did not confer a TH17 anti-inflammatory profile and Ahr−/− cells did not upregulate any TH17 pathogenic marker. Through the use of EAE model, we demonstrated that AHR is still functional in encephalitogenic CD4+ T cells and the adoptive transfer of Ahr−/− TH17 cells to recipient mice resulted in milder EAE development when compared to their WT counterparts. Altogether, our data demonstrated that although AHR is highly expressed on in vitro-generated nonpathogenic TH17 cells, its ligation does not shift TH17 cells to an anti-inflammatory phenotype. Further studies investigating the role of AHR beyond TH17 differentiation may provide a useful understanding of the physiopathology of autoimmune diseases.
Renal tubular epithelial cells: the neglected mediator of tubulointerstitial fibrosis after injury
Authors: Qi Ruochen , Yang Cheng
Published: November 2018

Renal fibrosis, especially tubulointerstitial fibrosis, is the inevitable outcome of all progressive chronic kidney diseases (CKDs) and exerts a great health burden worldwide. For a long time, interests in renal fibrosis have been concentrated on fibroblasts and myofibroblasts. However, in recent years, growing numbers of studies have focused on the role of tubular epithelial cells (TECs). TECs, rather than a victim or bystander, are probably a neglected mediator in renal fibrosis, responding to a variety of injuries. The maladaptive repair mechanisms of TECs may be the key point in this process. In this review, we will focus on the role of TECs in tubulointerstitial fibrosis. We will follow the fate of a tubular cell and depict the intracellular changes after injury. We will then discuss how the repair mechanism of tubular cells becomes maladaptive, and we will finally discuss the intercellular crosstalk in the interstitium that ultimately proceeds tubulointerstitial fibrosis.
TBX2 is a neuroblastoma core regulatory circuitry component enhancing MYCN/FOXM1 reactivation of DREAM targets
Authors: Decaesteker Bieke , Denecker Geertrui , Van Neste Christophe , Dolman Emmy M. , Van Loocke Wouter , Gartlgruber Moritz , Nunes Carolina , De Vloed Fanny , Depuydt Pauline , Verboom Karen , Rombaut Dries , Loontiens Siebe , De Wyn Jolien , Kholosy Waleed M. , Koopmans Bianca , Essing Anke H. W. , Herrmann Carl , Dreidax Daniel , Durinck Kaat , Deforce Dieter , Van Nieuwerburgh Filip , Henssen Anton , Versteeg Rogier , Boeva Valentina , Schleiermacher Gudrun , van Nes Johan , Mestdagh Pieter , Vanhauwaert Suzanne , Schulte Johannes H. , Westermann Frank , Molenaar Jan J. , De Preter Katleen , Speleman Frank
Published: November 2018

Chromosome 17q gains are almost invariably present in high-risk neuroblastoma cases. Here, we perform an integrative epigenomics search for dosage-sensitive transcription factors on 17q marked by H3K27ac defined super-enhancers and identify TBX2 as top candidate gene. We show that TBX2 is a constituent of the recently established core regulatory circuitry in neuroblastoma with features of a cell identity transcription factor, driving proliferation through activation of p21-DREAM repressed FOXM1 target genes. Combined MYCN/TBX2 knockdown enforces cell growth arrest suggesting that TBX2 enhances MYCN sustained activation of FOXM1 targets. Targeting transcriptional addiction by combined CDK7 and BET bromodomain inhibition shows synergistic effects on cell viability with strong repressive effects on CRC gene expression and p53 pathway response as well as several genes implicated in transcriptional regulation. In conclusion, we provide insight into the role of the TBX2 CRC gene in transcriptional dependency of neuroblastoma cells warranting clinical trials using BET and CDK7 inhibitors.
Nutrient supply controls particulate elemental concentrations and ratios in the low latitude eastern Indian Ocean
Authors: Garcia Catherine A. , Baer Steven E. , Garcia Nathan S. , Rauschenberg Sara , Twining Benjamin S. , Lomas Michael W. , Martiny Adam C.
Published: November 2018

Variation in ocean C:N:P of particulate organic matter (POM) has led to competing hypotheses for the underlying drivers. Each hypothesis predicts C:N:P equally well due to regional co-variance in environmental conditions and biodiversity. The Indian Ocean offers a unique positive temperature and nutrient supply relationship to test these hypotheses. Here we show how elemental concentrations and ratios vary over daily and regional scales. POM concentrations were lowest in the southern gyre, elevated across the equator, and peaked in the Bay of Bengal. Elemental ratios were highest in the gyre, but approached Redfield proportions northwards. AsProchlorococcusdominated the phytoplankton community, biodiversity changes could not explain the elemental variation. Instead, our data supports the nutrient supply hypothesis. Finally, gyre dissolved iron concentrations suggest extensive iron stress, leading to depressed ratios compared to other gyres. We propose a model whereby differences in iron supply and N2-fixation influence C:N:P levels across ocean gyres.
Rapid and robust restoration of breathing long after spinal cord injury
Authors: Warren Philippa M. , Steiger Stephanie C. , Dick Thomas E. , MacFarlane Peter M. , Alilain Warren J. , Silver Jerry
Published: November 2018

There exists an abundance of barriers that hinder functional recovery following spinal cord injury, especially at chronic stages. Here, we examine the rescue of breathing up to 1.5 years following cervical hemisection in the rat. In spite of complete hemidiaphragm paralysis, a single injection of chondroitinase ABC in the phrenic motor pool restored robust and persistent diaphragm function while improving neuromuscular junction anatomy. This treatment strategy was more effective when applied chronically than when assessed acutely after injury. The addition of intermittent hypoxia conditioning further strengthened the ventilatory response. However, in a sub-population of animals, this combination treatment caused excess serotonergic (5HT) axon sprouting leading to aberrant tonic activity in the diaphragm that could be mitigated via 5HT2 receptor blockade. Through unmasking of the continuing neuroplasticity that develops after injury, our treatment strategy ensured rapid and robust patterned respiratory recovery after a near lifetime of paralysis.
Synthetic RNA-based logic computation in mammalian cells
Authors: Matsuura Satoshi , Ono Hiroki , Kawasaki Shunsuke , Kuang Yi , Fujita Yoshihiko , Saito Hirohide
Published: November 2018

Synthetic biological circuits are designed to regulate gene expressions to control cell function. To date, these circuits often use DNA-delivery methods, which may lead to random genomic integration. To lower this risk, an all RNA system, in which the circuit and delivery method are constituted of RNA components, is preferred. However, the construction of complexed circuits using RNA-delivered devices in living cells has remained a challenge. Here we show synthetic mRNA-delivered circuits with RNA-binding proteins for logic computation in mammalian cells. We create a set of logic circuits (AND, OR, NAND, NOR, and XOR gates) using microRNA (miRNA)- and protein-responsive mRNAs as decision-making controllers that are used to express transgenes in response to intracellular inputs. Importantly, we demonstrate that an apoptosis-regulatory AND gate that senses two miRNAs can selectively eliminate target cells. Thus, our synthetic RNA circuits with logic operation could provide a powerful tool for future therapeutic applications.
Sumoylation of RORγt regulates TH17 differentiation and thymocyte development
Authors: He Zhiheng , Zhang Jing , Huang Zhaofeng , Du Qian , Li Ning , Zhang Qiang , Chen Yuan , Sun Zuoming
Published: November 2018

RORγt controls the differentiation of TH17 cells, which are mediators of autoimmune conditions such as experimental autoimmune encephalomyelitis (EAE). RORγt also regulates thymocyte development and lymph node genesis. Here we show that the function of RORγt is regulated by its sumoylation. Loss of Sumo3, but not Sumo1, dampens TH17 differentiation and delays the progression of thymic CD8+ immature single-positive cells (ISPs). RORγt is SUMO3-modified by E3 ligase PIAS4 at lysine 31 (K31), and the mutation of K31 to arginine in mice prevents RORγt sumoylation, leading to impaired TH17 differentiation, resistance to TH17-mediated EAE, accumulation of thymic ISPs, and a lack of Peyer’s patches. Mechanistically, sumoylation of RORγt-K31 recruits histone acetyltransferase KAT2A, which stabilizes the binding of SRC1 to enhance RORγt transcription factor activity. This study thus demonstrates that sumoylation is a critical mechanism for regulating RORγt function, and reveals new drug targets for preventing TH17-mediated autoimmunity.
Cell metabolism regulates integrin mechanosensing via an SLC3A2-dependent sphingolipid biosynthesis pathway
Authors: Boulter Etienne , Estrach Soline , Tissot Floriane S. , Hennrich Marco L. , Tosello Lionel , Cailleteau Laurence , de la Ballina Laura R. , Pisano Sabrina , Gavin Anne-Claude , Féral Chloé C.
Published: November 2018

Mechanical and metabolic cues independently contribute to the regulation of cell and tissue homeostasis. However, how they cross-regulate each other during this process remains largely unknown. Here, we show that cellular metabolism can regulate integrin rigidity-sensing via the sphingolipid metabolic pathway controlled by the amino acid transporter and integrin coreceptor CD98hc (SLC3A2). Genetic invalidation of CD98hc in dermal cells and tissue impairs rigidity sensing and mechanical signaling downstream of integrins, including RhoA activation, resulting in aberrant tissue mechanical homeostasis. Unexpectedly, we found that this regulation does not occur directly through regulation of integrins by CD98hc but indirectly, via the regulation of sphingolipid synthesis and the delta-4-desaturase DES2. Loss of CD98hc decreases sphingolipid availability preventing proper membrane recruitment, shuttling and activation of upstream regulators of RhoA including Src kinases and GEF-H1. Altogether, our results unravel a novel cross-talk regulation between integrin mechanosensing and cellular metabolism which may constitute an important new regulatory framework contributing to mechanical homeostasis.
Molecular basis of maintaining an oxidizing environment under anaerobiosis by soluble fumarate reductase
Authors: Kim Sunghwan , Kim Chang Min , Son Young-Jin , Choi Jae Young , Siegenthaler Rahel K. , Lee Younho , Jang Tae-Ho , Song Jaeyoung , Kang Hara , Kaiser Chris A. , Park Hyun Ho
Published: November 2018

Osm1 and Frd1 are soluble fumarate reductases from yeast that are critical for allowing survival under anaerobic conditions. Although they maintain redox balance during anaerobiosis, the underlying mechanism is not understood. Here, we report the crystal structure of a eukaryotic soluble fumarate reductase, which is unique among soluble fumarate reductases as it lacks a heme domain. Structural and enzymatic analyses indicate that Osm1 has a specific binding pocket for flavin molecules, including FAD, FMN, and riboflavin, catalyzing their oxidation while reducing fumarate to succinate. Moreover, ER-resident Osm1 can transfer electrons from the Ero1 FAD cofactor to fumarate either by free FAD or by a direct interaction, allowing de novo disulfide bond formation in the absence of oxygen. We conclude that soluble eukaryotic fumarate reductases can maintain an oxidizing environment under anaerobic conditions, either by oxidizing cellular flavin cofactors or by a direct interaction with flavoenzymes such as Ero1.
Wnt/β-catenin signaling regulates VE-cadherin-mediated anastomosis of brain capillaries by counteracting S1pr1 signaling
Authors: Hübner Kathleen , Cabochette Pauline , Diéguez-Hurtado Rodrigo , Wiesner Cora , Wakayama Yuki , Grassme Kathrin S. , Hubert Marvin , Guenther Stefan , Belting Heinz-Georg , Affolter Markus , Adams Ralf H. , Vanhollebeke Benoit , Herzog Wiebke
Published: November 2018

Canonical Wnt signaling is crucial for vascularization of the central nervous system and blood-brain barrier (BBB) formation. BBB formation and modulation are not only important for development, but also relevant for vascular and neurodegenerative diseases. However, there is little understanding of how Wnt signaling contributes to brain angiogenesis and BBB formation. Here we show, using high resolution in vivo imaging and temporal and spatial manipulation of Wnt signaling, different requirements for Wnt signaling during brain angiogenesis and BBB formation. In the absence of Wnt signaling, premature Sphingosine-1-phosphate receptor (S1pr) signaling reduces VE-cadherin and Esama at cell-cell junctions. We suggest that Wnt signaling suppresses S1pr signaling during angiogenesis to enable the dynamic junction formation during anastomosis, whereas later S1pr signaling regulates BBB maturation and VE-cadherin stabilization. Our data provides a link between brain angiogenesis and BBB formation and identifies Wnt signaling as coordinator of the timing and as regulator of anastomosis.
Flow of cerebrospinal fluid is driven by arterial pulsations and is reduced in hypertension
Authors: Mestre Humberto , Tithof Jeffrey , Du Ting , Song Wei , Peng Weiguo , Sweeney Amanda M. , Olveda Genaro , Thomas John H. , Nedergaard Maiken , Kelley Douglas H.
Published: November 2018

Flow of cerebrospinal fluid (CSF) through perivascular spaces (PVSs) in the brain is important for clearance of metabolic waste. Arterial pulsations are thought to drive flow, but this has never been quantitatively shown. We used particle tracking to quantify CSF flow velocities in PVSs of live mice. CSF flow is pulsatile and driven primarily by the cardiac cycle. The speed of the arterial wall matches that of the CSF, suggesting arterial wall motion is the principal driving mechanism, via a process known as perivascular pumping. Increasing blood pressure leaves the artery diameter unchanged but changes the pulsations of the arterial wall, increasing backflow and thereby reducing net flow in the PVS. Perfusion-fixation alters the normal flow direction and causes a 10-fold reduction in PVS size. We conclude that particle tracking velocimetry enables the study of CSF flow in unprecedented detail and that studying the PVS in vivo avoids fixation artifacts.
Two-dimensional tessellation by molecular tiles constructed from halogen–halogen and halogen–metal networks
Authors: Cheng Fang , Wu Xue-Jun , Hu Zhixin , Lu Xuefeng , Ding Zijing , Shao Yan , Xu Hai , Ji Wei , Wu Jishan , Loh Kian Ping
Published: November 2018

Molecular tessellations are often discovered serendipitously, and the mechanisms by which specific molecules can be tiled seamlessly to form periodic tessellation remain unclear. Fabrication of molecular tessellation with higher symmetry compared with traditional Bravais lattices promises potential applications as photonic crystals. Here, we demonstrate that highly complex tessellation can be constructed on Au(111) from a single molecular building block, hexakis(4-iodophenyl)benzene (HPBI). HPBI gives rise to two self-assembly phases on Au(111) that possess the same geometric symmetry but different packing densities, on account of the presence of halogen-bonded and halogen–metal coordinated networks. Sub-domains of these phases with self-similarity serve as tiles in the periodic tessellations to express polygons consisting of parallelograms and two types of triangles. Our work highlights the important principle of constructing multiple phases with self-similarity from a single building block, which may constitute a new route to construct complex tessellations.
Effective connectivity of the anterior hippocampus predicts recollection confidence during natural memory retrieval
Authors: Ren Yudan , Nguyen Vinh T. , Sonkusare Saurabh , Lv Jinglei , Pang Tianji , Guo Lei , Eickhoff Simon B. , Breakspear Michael , Guo Christine C.
Published: November 2018

Human interactions with the world are influenced by memories of recent events. This effect, often triggered by perceptual cues, occurs naturally and without conscious effort. However, the neuroscience of involuntary memory in a dynamic milieu has received much less attention than the mechanisms of voluntary retrieval with deliberate purpose. Here, we investigate the neural processes driven by naturalistic cues that relate to, and presumably trigger the retrieval of recent experiences. Viewing the continuation of recently viewed clips evokes greater bilateral activation in anterior hippocampus, precuneus and angular gyrus than naïve clips. While these regions manifest reciprocal connectivity, continued viewing specifically modulates the effective connectivity from the anterior hippocampus to the precuneus. The strength of this modulation predicts participants’ confidence in later voluntary recall of news details. Our study reveals network mechanisms of dynamic, involuntary memory retrieval and its relevance to metacognition in a rich context resembling everyday life.
Publisher Correction: Complex virome in feces from Amerindian children in isolated Amazonian villages
Authors: Siqueira Juliana D. , Dominguez-Bello Maria Gloria , Contreras Monica , Lander Orlana , Caballero-Arias Hortensia , Xutao Deng , Noya-Alarcon Oscar , Delwart Eric
Published: November 2018

In the original version of this Article, the affiliation details for Eric Delwart were incorrectly given as ‘Blood Systems Research Institute, San Francisco, CA 94118, USA and Amazonic Center for Research and Control of Tropical Diseases (CAICET), Puerto Ayacucho 7101, Venezuela’. The correct affiliations are ‘Blood Systems Research Institute, San Francisco, CA 94118, USA and Department of Laboratory Medicine, University of California at San Francisco, San Francisco, CA 94118, USA’. This has been corrected in both the PDF and HTML versions of the Article.
Vimentin deficiency in macrophages induces increased oxidative stress and vascular inflammation but attenuates atherosclerosis in mice
Authors: Håversen Liliana , Sundelin Jeanna Perman , Mardinoglu Adil , Rutberg Mikael , Ståhlman Marcus , Wilhelmsson Ulrika , Hultén Lillemor Mattsson , Pekny Milos , Fogelstrand Per , Bentzon Jacob Fog , Levin Malin , Borén Jan
Published: November 2018

The aim was to clarify the role of vimentin, an intermediate filament protein abundantly expressed in activated macrophages and foam cells, in macrophages during atherogenesis. Global gene expression, lipid uptake, ROS, and inflammation were analyzed in bone-marrow derived macrophages from vimentin-deficient (Vim−/−) and wild-type (Vim+/+) mice. Atherosclerosis was induced in Ldlr−/− mice transplanted with Vim−/− and Vim+/+ bone marrow, and in Vim−/− and Vim+/+ mice injected with a PCSK9 gain-of-function virus. The mice were fed an atherogenic diet for 12–15 weeks. We observed impaired uptake of native LDL but increased uptake of oxLDL in Vim−/− macrophages. FACS analysis revealed increased surface expression of the scavenger receptor CD36 on Vim−/− macrophages. Vim−/− macrophages also displayed increased markers of oxidative stress, activity of the transcription factor NF-κB, secretion of proinflammatory cytokines and GLUT1-mediated glucose uptake. Vim−/− mice displayed decreased atherogenesis despite increased vascular inflammation and increased CD36 expression on macrophages in two mouse models of atherosclerosis. We demonstrate that vimentin has a strong suppressive effect on oxidative stress and that Vim−/− mice display increased vascular inflammation with increased CD36 expression on macrophages despite decreased subendothelial lipid accumulation. Thus, vimentin has a key role in regulating inflammation in macrophages during atherogenesis.