bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromosome-scale assembly of theSparassis latifoliagenome obtained using long-read and Hi-C sequencing
Authors: Yang Chi , Ma Lu , Xiao Donglai , Liu Xiaoyu , Jiang Xiaoling , Ying Zhenghe , Lin Yanquan
Published: January 2021

Sparassis latifoliais a valuable edible mushroom cultivated in China. In 2018, our research group reported an incomplete and low quality genome ofS. latifoliawas obtained by Illumina HiSeq 2500 sequencing. These limitations in the available genome have constrained genetic and genomic studies in this mushroom resource. Herein, an updated draft genome sequence ofS. latifoliawas generated by Oxford Nanopore sequencing and the Hi-C technique. A total of 8.24 Gb of Oxford Nanopore long reads representing ~198.08X coverage of theS. latifoliagenome were generated. Subsequently, a high-quality genome of 41.41 Mb, with scaffold and contig N50 sizes of 3.31 Mb and 1.51 Mb, respectively, was assembled. Hi-C scaffolding of the genome resulted in 12 pseudochromosomes containing 93.56% of the bases in the assembled genome. Genome annotation further revealed that 17.47% of the genome was composed of repetitive sequences. In addition, 13,103 protein-coding genes were predicted, among which 98.72% were functionally annotated. BUSCO assay results further revealed that there were 92.07% complete BUSCOs. The improved chromosome-scale assembly and genome features described here will aid further molecular elucidation of various traits, breeding ofS. latifolia, and evolutionary studies with related taxa.

Importance

Sparassis latifoliaY.C. Dai et Z. Wang (Sparassidaceae, Polyporales, Agaricomycetes), collections from AsianSparassis(Dai et al., 2006) exhibits diverse biological and pharmacologic activities. To date, total fresh fruit production in Chinese factories is over 20 tons/d. Despite the significant economic and medical value ofS. latifolia, the assembly level of genome was under chromosome-scale. This study assembles a high-quality chromosome-scale reference genome ofS. latifoliausing Oxford Nanopore sequencing combined with Hi-C (High-through chromosome conformation capture) scaffolding. The improved reference genome will facilitate molecular breeding ofS. latifoliaand advance our understanding of its genetics and evolution.
Epstein-Barr Virus Induced Cytidine Metabolism Roles in Transformed B-cell Growth and Survival
Authors: Liang Jin-Hua , Wang Chong , Tung Yiu Stephanie Pei , Zhao Bo , Guo Rui , Gewurz Benjamin E.
Published: January 2021

Epstein-Barr virus (EBV) is associated with 200,000 cancers annually, including B-cell lymphomas in immunosuppressed hosts. Hypomorphic mutations of thede novopyrimidine synthesis pathway enzyme cytidine 5’ triphosphate synthase 1 (CTPS1) suppress cell mediated immunity, resulting in fulminant EBV infection and EBV+ central nervous system (CNS) lymphomas. Since CTP is a critical precursor for DNA, RNA and phospholipid synthesis, this observation raises the question of whether the isozyme CTPS2 or cytidine salvage pathways help meet CTP demand in EBV-infected B-cells. Here, we found that EBV upregulated CTPS1 and CTPS2 with distinct kinetics in newly infected B-cells. While CRISPR CTPS1 knockout caused DNA damage and proliferation defects in lymphoblastoid cell lines (LCL), which express the EBV latency III program observed in CNS lymphomas, double CTPS1/2 knockout caused stronger phenotypes. EBNA2, MYC and non-canonical NF-□B positively regulated CTPS1 expression. CTPS1 depletion impaired EBV lytic DNA synthesis, suggesting that latent EBV may drive pathogenesis with CTPS1 deficiency. Cytidine rescued CTPS1/2 deficiency phenotypes in EBV-transformed LCL and Burkitt B-cells, highlighting CTPS1/2 as a potential therapeutic target for EBV-driven lymphoproliferative disorders. Collectively, our results suggest that CTPS1 and CTPS2 have partially redundant roles in EBV-transformed B-cells and provide insights into EBV pathogenesis with CTPS1 deficiency.
Chikungunya virus ECSA lineage reintroduction in the northeasternmost region of Brazil
Authors: Xavier Joilson , Fonseca Vagner , Bezerra Joao Felipe , do Monte Alves Manoella , Mares-Guia Maria Angélica , Claro Ingra Morales , de Jesus Ronaldo , Adelino Talita , Araújo Emerson , Jardim Cavalcante Karina Ribeiro Leite , Tosta Stephane , de Souza Themis Rocha , da Cruz Flavia Emanuelle Moreira , de Araújo Fabri Allison , de Oliveira Elaine Cristina , de Moura Noely Fabiana Oliveira , do Carmo Said Rodrigo Fabiano , de Albuquerque Carlos Frederico Campelo , Azevedo Vasco , de Oliveira Tulio , de Filippis Ana Maria Bispo , da Cunha Rivaldo Venâncio , Luz Kleber Giovanni , Giovanetti Marta , Junior Alcantara Luiz Carlos
Published: January 2021

The Northeast region of Brazil registered the second highest incidence proportion of chikungunya fever in 2019. In that year an outbreak consisting of patients presented with febrile disease associated with joint pain were reported by the public primary health care service in the city of Natal, Rio Grande do Norte state, in March 2019. At first, the aetiological agent of the disease was undetermined. Since much is still unknown about chikungunya virus (CHIKV) genomic diversity and evolutionary history in this northeasternmost state, we used a combination of portable whole genome sequencing, molecular clock, and epidemiological analyses that revealed the re-introduction of the CHIKV East-Central-South-African (ECSA) lineage into Rio Grande do Norte. We estimated CHIKV ECSA lineage was first introduced into Rio Grande do Norte in early June 2014, while the 2019 outbreak clade diverged around April 2018 during a period of increased chikungunya incidence in the Southeast region, which might have acted as a source of virus dispersion towards the Northeast region. Together, these results confirm the ECSA lineage continues to spread across the country through interregional importation events likely mediated by human mobility.

HIGHLIGHTS

CHIKV ECSA lineage introduction into Rio Grande do Norte state, Northeast Brazil, was estimated to early June 2014

At least two CHIKV importation events occurred in Rio Grande do Norte state, Brazil

The 2019 chikungunya outbreak in Rio Grande do Norte was likely caused by a second event of CHIKV introduction imported from Rio de Janeiro state.
Targeting EGFR in glioblastoma with a novel brain-penetrant small molecule EGFR-TKI
Authors: Ni Jing , Yang Yanzhi , Wang Qiwei , Bergholz Johann S. , Jiang Tao , Roberts Thomas M. , Gray Nathanael S. , Zhao Jean J.
Published: January 2021

Epidermal growth factor receptor (EGFR) is mutated or amplified in a majority of glioblastoma (GBM), and its mutation and focal amplification correlate with a more aggressive disease course. However, EGFR-directed tyrosine kinase inhibitors (TKIs) tested to date have yielded minimal clinical benefit. Here, we report a novel covalent-binding EGFR-TKI, CM93, as a potential drug to target adult GBMs with aberrant EGFR. CM93 has extraordinary brain exposure, with a brain-to-plasma ratio greater than 20-fold at estimated steady state. While all approved EGFR-TKIs are subject to extensive efflux transporter activity, CM93 does not inhibit the P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) efflux transporters in Caco-2 cells at expected clinically relevant plasma concentrations. Equally, CM93 demonstrates moderate absorption and permeation in Caco-2 cell monolayers with efflux ratios < 2, suggesting that it is not likely a substrate of an efflux transporter. Collectively, thesein vitrodata may account for the dramatic increase in brain exposure over plasma as noted above. Pre-clinical efficacy studies showed that CM93 is more effective than other EGFR-TKIs in blocking the proliferation of GBM tumor cells from both patient-derived and cultured human GBM cell lines with EGFR amplification and/or EGFRvIII mutation. In addition, CM93 administered as a single agent was able to attenuate the growth of orthotopic U251-EGFRvIII xenografts and extend the survival of tumor-bearing mice in a dose-dependent manner. Moreover, CM93 inhibited EGFR phosphorylation in GBM tumors derived from a novel genetically-engineered mouse (GEM) model of GBM with EGFRvIII expression bothin vitroandin vivo. CM93 also extended the survival of mice bearing orthotopic allografts of GBM. Notably, mice maintained stable body weight during treatments with increasing doses of CM93 up to 75 mg/kg per day. Together, these data suggest that CM93 is a potential EGFR-TKI well suited for the treatment of adult GBM with mutant EGFR.
Co-evolutionary Landscape at the Interface and Non-Interface Regions of Protein-Protein Interaction Complexes
Authors: Mukherjee Ishita , Chakrabarti Saikat
Published: January 2021

Proteins involved in interactions throughout the course of evolution tend to co-evolve and compensatory or coordinated changes may occur in interacting proteins to maintain or refine interactions between them. However, certain residue pair alterations may prove to be detrimental for functional interactions. Hence, determining co-evolutionary pairings that could be structurally or functionally relevant for maintaining the conservation of an inter-protein interaction is important. Inter-protein co-evolution analysis in a number of complexes with the help of multiple existing methodologies suggested that co-evolutionary pairings can occur in spatially proximal as well as distant regions of inter-protein interaction complexes. Subsequently, the Co-Var (CorrelatedVariation) method based on mutual information and Bhattacharyya coefficient was developed, validated and found to perform relatively better than CAPS and EV-complex. Interestingly, while applying the Co-Var measure on a set of protein-protein interaction complexes, co-evolutionary pairings were obtained in spatially proximal and distant regions in inter-protein complexes. Our approach involves determining high degree co-evolutionary pairings which include multiple co-evolutionary connections between particular co-evolved residue positions in one protein and particular residue positions in the binding partner. Detailed analyses of high degree co-evolutionary pairings in protein-protein complexes involved in inter-cellular communication during cancer metastasis were performed. These analyses suggested that most of the residue positions involved in such co-evolutionary pairings mainly occurred within functional domains of constituent proteins and substitution mutations were also common among these co-evolved positions. The physiological relevance of these predictions suggests that Co-Var can predict residues that could be crucial for preserving functional protein-protein interactions. Finally,Co-Varweb server that implements this methodology was developed. This web server available athttp://www.hpppi.iicb.res.in/ishi/covar/index.htmlidentifies co-evolutionary pairings in intra-protein and inter-protein complexes.
Staphylococcal enterotoxin B‐ and lipopolysaccharide‐induced toxic shock syndrome in a burn patient
Authors: Yamasaki Osamu , Sugihara Satoru , Kajita Ai , Yokoyama Emi , Miyake Tomoko , Hirai Yoji , Morizane Shin
Published: January 2021

Toxic shock syndrome (TSS) is caused by toxic shock syndrome toxin 1 or enterotoxins secreted by Staphylococcus aureus. Lipopolysaccharide (LPS) has also been shown to play a major role in the development of sepsis. Staphylococcal superantigens and LPS operate synergistically in conditioning cytokine release and lethal shock in mice. An 80‐year‐old woman was admitted because of a 20% mixed‐depth flame burn. Despite two excisions and grafts, necrotic ulcers with methicillin‐resistant Staphylococcus aureus (MRSA) colonization remained. On the 7th day after the operation, she developed shock with an erythematous rash. Blood examination revealed evidence of disseminated intravascular coagulation, and liver and renal dysfunction. A blood culture revealed a staphylococcal enterotoxin B (SEB)‐producing strain of MRSA and Klebsiella pneumoniae. The septic symptoms were prolonged, but the condition gradually improved with extensive treatment. T‐cell receptor analysis demonstrated a marked accumulation of SEB‐mediated Vβ T cells. Stimulation of peripheral blood mononuclear cells in the recovery phase with SEB and LPS induced additive effects on tumor necrosis factor‐α, interferon‐γ, and interleukin‐6 production. Although the present case did not fulfill the clinical criteria for TSS, the additive effects of SEB and LPS might have caused the severe septic shock.
Elevation is a stronger predictor of morphological trait divergence than competition in a radiation of tropical lizards
Authors: Slavenko Alex , Allison Allen , Meiri Shai
Published: January 2021

Adaptations for efficient performance are expected to shape animal morphology based on selection for microhabitat use and ecological forces. The presence of competitor species is predicted to cause niches to contract and enhance trait divergence. Therefore, increased species richness is expected to lead to greater trait divergence, and to result in reduced overlap and similarity between morphologies of sympatric species.

We examined patterns of morphospace occupancy and partitioning in the skink fauna of New Guinea, the world's largest tropical island. Because skink species richness is largely decoupled from elevation in New Guinea, we could examine the effects of both factors (as proxies for competition and abiotic conditions), on morphospace occupancy and partitioning.

We measured 1,860 specimens from 79 species of skinks throughout Papua New Guinea, and examined their morphospace occupancy in a spatial context. We calculated, for each assemblage within equal‐area cells, the volume of morphospace occupied by all skinks, the mean volume occupied per species, and the mean distance and overlap between all species pairs. We then examined whether these metrics are related to species richness and elevation.

Elevation is a stronger predictor of morphospace occupancy than species richness. As elevation increases, intraspecific variation decreases and morphologies become more similar to each other such that overall morphospace occupancy decreases. Highland skinks are, on average, smaller, thinner and shorter limbed than lowland species.

We hypothesise that harsh climates in the New Guinea highland habitats impose strong selection on skinks to occupy specific areas of morphospace that facilitate efficient thermoregulation in suboptimal thermal conditions. We conclude that the effect of competition on trait divergence on a community and assemblage scale is eclipsed by abiotic selection pressures in these harsh environments.
Common‐garden experiment reveals clinal trends of bud phenology in black spruce populations from a latitudinal gradient in the boreal forest
Authors: Guo Xiali , Klisz Marcin , Puchałka Radosław , Silvestro Roberto , Faubert Patrick , Belien Evelyn , Huang Jianguo , Rossi Sergio
Published: January 2021

Climate warming is modifying the movement of air masses over Northern latitudes, producing warming and cooling events across the boreal regions. These new conditions changes may mismatch plant phenology from weather conditions, and affect the growing period of trees. Understanding the processes of local adaptation in bud phenology can help to predict the response of plants to these rapid and unexpected environmental changes.

Our study monitored bud burst and bud set weekly during four growing seasons in black spruce [Picea mariana (Mill.) B.S.P.] saplings planted in a common garden and originating from five provenances representing the whole latitudinal distribution of the closed boreal forest in Quebec, Canada. We compared the variance in bud phenology among populations and years, and analysed the relationships with temperatures at the origin sites.

Bud burst and bud set occurred in mid‐May and mid‐July, respectively, with a large variability among provenances and between the study years. A delayed bud phenology was observed in the provenances from warmer sites, with bud burst and bud set being 1.1 and 1.4 days later for every additional degree in mean annual temperature at the origin site respectively. Populations with earlier bud bursts also showed earlier bud sets, thus the growing season was similar among provenances. The heritability of bud set was higher than that of bud burst, with estimates of 0.26 and 0.21 respectively. On average, variance in bud phenology among provenances reached 5.3%, which was higher than that within provenances (2.6%). The factor year explained 37.7%–69.7% of the variance in bud phenology.

Synthesis. The findings demonstrate the evolutionary response to climate variations in the boreal biome. Endogenous and environmental components have different effects on the phases of bud burst and bud set. This complex interaction among drivers of bud phenology may prevent reliable predictions of changes in the growing season under changing climate. An earlier growth reactivation due to higher spring temperatures could result in higher frost risks to the developing buds. Despite a longer period for photosynthesis expected for the evergreen black spruce under warmer conditions, the period spent for bud development could remain unchanged.
Ouverture commerciale, institutions du marché du travail et emploi des jeunes en Afrique
Authors: Kpognon Koffi , Atangana Ondoa Henri , Bah Mamadou , Messe Marie Fanny
Published: January 2021

L'objectif de ce travail est de mesurer l'effet de l'ouverture commerciale et des institutions du marché du travail sur l'emploi des jeunes en Afrique. Pour ce faire, nous avons considéré un ensemble de 38 pays sur la période 2000–2018. Les méthodes d'estimation utilisées portent sur les moindres carrés ordinaires (MCO), la méthode instrumentale (doubles moindres carrés‐2SLS) et la méthode des moments généralisés en système (MMG‐système). Les résultats révèlent que l'ouverture commerciale et la rigidité des institutions du marché du travail ont un effet positif et significatif sur l'emploi des jeunes en Afrique. Par contre, l'ouverture commerciale affecte négativement et significativement l'emploi des jeunes sur les marchés du travail rigides. Ces résultats sont valides face à plusieurs tests de robustesse.
‘A Rather Undefined Social Position and Public Recognition’: Professionalisation, Status and Masculinity in Provincial Museums, c.1870–1930
Authors: Hill Kate
Published: January 2021

This article examines the background, careers and self‐presentation of the first generation of British museum curators in local government‐funded provincial museums, c.1900, to explore the issue of masculinity among the lower‐middle classes. It argues that while such men were sometimes mocked for the lack of masculinity they showed in their domestic lives, a focus on their professional lives reveals a different set of problems facing them as they attempted to be manly men; curatorial roles, like others available to the lower‐middle classes, involved a dependence on local elites, and required many of the skills and attributes which were being colonised by new women professionals. The study then examines the tactics used, with some success, by such men to assert a professional masculinity, focusing on their identification with their museum, their development of a professional body and their investment in manly physical activities.
Artisanal Fresco cheese from Sonora: Physicochemical composition, microbial quality, and bacterial characterization by high‐throughput sequencing
Authors: Méndez‐Romero José I , Reyes‐Díaz Ricardo , Santiago‐López Lourdes , Hernández‐Mendoza Adrian , Vallejo‐Cordoba Belinda , Sayago‐Ayerdi Sonia G , Gómez‐Gil Bruno , González‐Córdova Aarón F
Published: January 2021

The aim of the present study was to characterise the physicochemical and the microbiota composition of the artisanal Fresco cheese from Sonora. For this, cheeses of 18 small‐scale artisanal dairies were analysed. The chemical composition and the microbiological quality were determined by standard methods, and bacterial diversity by high‐throughput sequencing. The physicochemical composition showed differences (P < 0.05) among dairies, and the principal component analysis aggrupation of 66% dairies. The analysis by region did not show difference (P < 0.05).The microbiota most abundant were Firmicutes, Proteobacteria and lactic acid bacteria in phyla and genera, respectively. These results provide insights on the characterisation of the Fresco cheese from Sonora.
Recent progress in mycotoxins detection based on surface‐enhanced Raman spectroscopy
Authors: Zhai Wenlei , You Tianyan , Ouyang Xihui , Wang Meng
Published: January 2021

Mycotoxins are toxic compounds naturally produced by certain types of fungi. The contamination of mycotoxins can occur on numerous foodstuffs, including cereals, nuts, fruits, and spices, and pose a major threat to humans and animals by causing acute and chronic toxic effects. In this regard, reliable techniques for accurate and sensitive detection of mycotoxins in agricultural products and food samples are urgently needed. As an advanced analytical tool, surface‐enhanced Raman spectroscopy (SERS), presents several major advantages, such as ultrahigh sensitivity, rapid detection, fingerprint‐type information, and miniaturized equipment. Benefiting from these merits, rapid growth has been observed under the topic of SERS‐based mycotoxin detection. This review provides a comprehensive overview of the recent achievements in this area. The progress of SERS‐based label‐free detection, aptasensor, and immunosensor, as well as SERS combined with other techniques, has been summarized, and in‐depth discussion of the remaining challenges has been provided, in order to inspire future development of translating the techniques invented in scientific laboratories into easy‐to‐operate analytic platforms for rapid detection of mycotoxins.
Pulse seeds as promising and sustainable source of ingredients with naturally bioencapsulated nutrients: Literature review and outlook
Authors: Pallares Pallares Andrea , Gwala Shannon , Pälchen Katharina , Duijsens Dorine , Hendrickx Marc , Grauwet Tara
Published: January 2021

Pulse seeds are nutritious and sustainable matrices with a high level of intrinsic microstructural complexity. They contain high‐quality plant‐based protein and substantial amounts of slowly digestible starch and dietary fiber. Starch and protein in pulses are located inside cotyledon cells that survive cooking and subsequent mechanical disintegration, hence preserving natural nutrient bioencapsulation. In this context, several authors have explored a number of techniques to isolate individual cotyledon cells from these seeds, aiming to unveil their digestive and physicochemical properties. In recent years, isolated pulse cotyledon cells are also being highlighted as promising novel ingredients that could improve the nutritional properties of traditionally consumed food products. Even more, they could enable to implement a strategy for increasing pulse intake in populations where these seeds have not been traditionally consumed. This review mainly focuses on the reported digestive, physicochemical, and technofunctional properties of pulse cotyledon cells isolated through different techniques, preceded by a descriptive summary of the nutritional properties, structural organization, and traditional process chain of pulse seeds. It also offers an outlook of research directions to take, based on the identified research gaps. All in all, it is clear that isolation of pulse cotyledon cells using diverse techniques constitutes a promising strategy for the development of pulse‐based ingredients where natural bioencapsulation of macronutrients is preserved. However, much more research is needed at the level of ingredient characterization to better understand the effect of starting pulse seed material, isolation technique, and isolation conditions on the nutritional and functional properties of the finished product(s) where the isolated cells are (to be) used.
Clinical fracture incidence of rotary and reciprocating NiTi files: A systematic review and meta‐regression
Authors: Gomes Maximiliano Schünke , Vieira Rosângela Mello , Böttcher Daiana Elisabeth , Plotino Gianluca , Celeste Roger Keller , Rossi‐Fedele Giampiero
Published: January 2021

This systematic review was registered in PROSPERO (CRD42017075917) and aimed to investigate whether the available clinical evidence supports the hypothesis that reciprocating motion results in a lower incidence of nickel‐titanium files fracture compared to continuous rotation. Clinical studies that reported the incidence of fracture of engine‐driven nickel‐titanium files were included. The main exposure was the kinematics, and the primary outcome was the incidence of files fracture. The overall incidence of files fracture was 2.27%, with a trend for higher incidence with rotary motion (2.43%) than with reciprocating (1.0%), though without significant differences. Multiple meta‐regression models revealed that the use of nickel‐titanium files in more than four teeth and less proficient operators were associated with a higher incidence of file fracture. There was no difference in the clinical incidence of fracture of nickel‐titanium instruments between reciprocating and rotary motions; however, other factors were identified.
Influence of morphometric parameters on the size of collateral ligaments of the distal interphalangeal joint of equines
Authors: Góss Geórgia Camargo , Mozzaquatro Fabricio Desconsi , Vanhove Raphaela , Camargo Lilian Pinto , Döwich Pradella Gabriela , Leite Carla Teixeira , Gomes Etiele Maldonado , Carneiro Ana Luisa Moreira , Heckler Gabriel Feix , Duarte Claudia Acosta
Published: January 2021

The physiological measurements of collateral ligaments of distal interphalangeal joint (CL‐DIPJ) differ in the literature. The factors that influence these differences are not well described. The aims of this study are to compare CL‐DIPJ sizes in equines with different withers height, as well as to correlate body weight and hoof size to the size of these ligaments. In total, 52 horses were used in the study. They were divided into two groups according to wither height: Group 1 (G1) ‐ 21 animals with up to 147 cm ‐ and group 2 (G2) ‐ 21 animals with greater than 148 cm. CL‐DIPJ was ultrasonographically measured in order to find the mean of dorso‐palmar (DPD) and latero‐medial (LMD) diameters and the cross‐sectional area (CSA). Hoof width and length were measured, and the results were used to calculate the hoof surface area. Withers height and body weight were also measured. Groups were statistically compared by Student's t test and Pearson's correlation application to each group. Groups were different in body size, HS and CL‐DIPJ size when p < .05, except for the LMD of the medial collateral ligament of left thoracic limb. Withers height and body weight did not show significant correlations to CL‐DIPJ size in G1, but they had little influence on the size of CL‐DIPJ on G2. No correlation between the hoof size and the CL‐DIPJ was noted in any of the two groups. In conclusion, the CL‐DIPJ were larger in taller horses and their sizes were correlated to their height and weight, but they were not correlated to hoof size.
The low cytotoxic activity of peripheral blood NK cells may relate to unexplained recurrent miscarriage
Authors: Zhang Yongnu , Huang Chunyu , Lian Ruochun , Xu Jian , Fu Yunfeng , Zeng Yong , Tu Wenwei
Published: January 2021

Problem

Unexplained recurrent miscarriage (uRM) is defined as two or more spontaneous abortions prior to 20 weeks of gestation with unknown etiology. Peripheral blood natural killer (pNK) cells contact with the villus and exert important role in normal pregnancy. However, it is still controversial about the association between pNK cytotoxicity and uRM, and the underlying mechanism remains unknown so far.

Method of Study

In this study, we aim to compare the percentage, immunophenotype, and function of pNK cells between patients with uRM and fertile controls. The peripheral blood was collected from 49 patients with uRM and 11 fertile women in their middle luteal phase of the menstrual cycle. pNK cells were co‐cultured with K562 cells at different cell ratios to measure the cytotoxicity. The percentage of CD3−CD56+, CD3−CD56bright, and CD3−CD56dim pNK was analyzed by flow cytometry and quantified to evaluate the expression of cytotoxic granules (granzyme B, granulysin, and perforin), and the cell surface receptors related to pNK cell cytotoxicity (NKG2D, NKp30, NKp46, CD158a, and CD158b) were also detected.

Results

The general linear model analysis showed that pNK cell cytotoxicity in patients with uRM was significantly lower than that in fertile controls. In addition, the ratios of NKG2D/CD158a, NKp30/CD158a, and NKp46/CD158a in CD3−CD56bright pNK subsets were significantly lower in uRM group than that in fertile control. The logistical regression analysis showed that the reduced NKp30/CD158a, NKp46/CD158a ratios in CD3−CD56bright pNK subsets were significantly associated with uRM.

Conclusion

Our results suggested that a low pNK cytotoxicity, which is mediated by inhibitory signals, might be associated with uRM.
Reconciliation 2.0: Resolving Contradictions in the Production of Settler Colonial and Capitalist Space in Canada
Authors: Van Lier Nicole
Published: January 2021

This paper reviews a pair of Canadian legal decisions on the duty to consult to explore the court’s role in reconciling tensions between settler colonial and capitalist space. Following a period of political and economic instability that made energy development vulnerable to Indigenous legal challenge, the court legalised the delegation of Indigenous consultations to corporate and regulatory actors, defined consultation in practical terms, and intensified the remedy for inadequate consultation. The court not only substituted nation‐to‐nation negotiations with corporate engagements, but submitted energy corporations to the work of legitimising and effectuating Canadian sovereignty. The decisions call for an expanded view of “reconciliation” as a judicial practice of Indigenous dispossession, accomplished not only by reconciling Indigenous authority with Canadian sovereignty, but by reconciling capitalist energy development with the legalities of Canada’s modern settler colonial order. The decisions bring into greater focus the state’s increasing reliance on corporations to reproduce Canadian sovereignty.
Blogging the Virtual: New Geographies of Domination and Resistance In and Beyond Russia
Authors: Wolfe Sven Daniel
Published: January 2021

Russia’s accelerating authoritarian turn has not ignored the internet, and in recent years, the Russian state has clamped down on internet activities that diverge from the statist line, employing a variety of strategies to dominate online spaces. Nevertheless, oppositional voices flourish on the Russian internet, taking shape in independent blogs and videos. This paper explores three political bloggers through surveillant and resistance assemblages, making sense of this contestation through an interpretation of the Deleuzian virtual that underscores the emancipatory potential of online activities for producing more egalitarian configurations, but also taking stock of the ways that these technologies have increased domination. Encompassing the blurriness between digital and corporeal spaces, the paper contributes by revealing new geographies of contestation against state strategies to dominate the Russian internet. Overlapping with but not corresponding to Russian territorial boundaries, these dynamics highlight shifting spaces of power and resistance in the increasingly illiberal world.
Combined use of infrared imaging techniques for the study of underlying features in the Santa Maria in Cosmedin altarpiece
Authors: Mercuri F. , Ceccarelli S. , Orazi N. , Cicero C. , Paoloni S. , Felici A. C. , Matera F. , Nuzzo M. , Zammit U.
Published: January 2021

This paper presents a study carried out on the painted altarpiece preserved inside the Basilica of Santa Maria in Cosmedin, Rome, by combining three imaging techniques operating in the near‐ and mid‐infrared spectral ranges. The altarpiece has several pictorial layers and restorations, which have superimposed over time for stylistic adjustment and conservative purposes up to its present appearance. The results obtained in this study enable the detection of damage to the wooden support and the identification of pictorial features buried beneath the visible paint layer, thus providing significant information on the historical and artistic characterization of the artefact.
Salt–magma interactions influence intrusion distribution and salt tectonics in the Santos Basin, offshore Brazil
Authors: Magee Craig , Pichel Leonardo M. , Madden‐Nadeau Amber L. , Jackson Christopher A.‐L. , Mohriak Webster
Published: January 2021

Many sedimentary basins host thick evaporite (salt) deposits. Some of these basins also host extensive igneous intrusion networks. It thus seems inevitable that, in some locations, magma will interact with salt. Yet how interaction between these materials may influence salt tectonics or magma emplacement, particularly at the basin‐scale, remains poorly understood. We use 3D seismic reflection data from the Santos Basin, offshore Brazil to image 38 igneous intrusions spatially related to thick Aptian salt. Based on identified seismic–stratigraphic relationships, we suggest sill emplacement likely occurred during the late Albian‐to‐Santonian. We show intra‐salt sills are geometrically similar to but laterally offset from supra‐salt sills. We suggest ascending magma was arrested by the salt in some areas, but not others, perhaps due to differences in evaporite lithology. Our mapping also reveals most sills occur within and above the presalt Merluza Graben, an area characterized by Albian‐to‐Neogene, salt‐detached extension. In adjacent areas, where there are few intrusions, salt deformation was driven by post‐Santonian diapir rise. We suggest emplacement of hot magma within evaporites above the Merluza Graben enhanced Albian‐to‐Santonian salt movement, but that crystallization of the intrusion network restricted post‐Santonian diapirism. Our work indicates salt–magma interaction can influence salt tectonics, as well as the distribution of magma plumbing systems, and thus could impact basin evolution.
VEGFR2 blockade augments the effects of tyrosine kinase inhibitors by inhibiting angiogenesis and oncogenic signaling in oncogene‐driven non‐small‐cell lung cancers
Authors: Watanabe Hiromi , Ichihara Eiki , Kayatani Hiroe , Makimoto Go , Ninomiya Kiichiro , Nishii Kazuya , Higo Hisao , Ando Chihiro , Okawa Sachi , Nakasuka Takamasa , Kano Hirohisa , Hara Naofumi , Hirabae Atsuko , Kato Yuka , Ninomiya Takashi , Kubo Toshio , Rai Kammei , Ohashi Kadoaki , Hotta Katsuyuki , Tabata Masahiro , Maeda Yoshinobu , Kiura Katsuyuki
Published: January 2021

Molecular agents targeting the epidermal growth factor receptor (EGFR)‐, anaplastic lymphoma kinase (ALK)‐ or c‐ros oncogene 1 (ROS1) alterations have revolutionized the treatment of oncogene‐driven non‐small‐cell lung cancer (NSCLC). However, the emergence of acquired resistance remains a significant challenge, limiting the wider clinical success of these molecular targeted therapies. In this study, we investigated the efficacy of various molecular targeted agents, including erlotinib, alectinib, and crizotinib, combined with anti‐vascular endothelial growth factor receptor (VEGFR) 2 therapy. The combination of VEGFR2 blockade with molecular targeted agents enhanced the anti‐tumor effects of these agents in xenograft mouse models of EGFR‐, ALK‐, or ROS1‐altered NSCLC. The numbers of CD31‐positive blood vessels were significantly lower in the tumors of mice treated with an anti‐VEGFR2 antibody combined with molecular targeted agents compared with in those of mice treated with molecular targeted agents alone, implying the antiangiogenic effects of VEGFR2 blockade. Additionally, the combination therapies exerted more potent antiproliferative effects in vitro in EGFR‐, ALK‐, or ROS1‐altered NSCLC cells, implying that VEGFR2 inhibition also has direct anti‐tumor effects on cancer cells. Furthermore, VEGFR2 expression was induced following exposure to molecular targeted agents, implying the importance of VEGFR2 signaling in NSCLC patients undergoing molecular targeted therapy. In conclusion, VEGFR2 inhibition enhanced the anti‐tumor effects of molecular targeted agents in various oncogene‐driven NSCLC models, not only by inhibiting tumor angiogenesis but also by exerting direct antiproliferative effects on cancer cells. Hence, combination therapy with anti‐VEGFR2 antibodies and molecular targeted agents could serve as a promising treatment strategy for oncogene‐driven NSCLC.
Capturing Environmental Dimensions of Adversity and Resources in the Context of Poverty Across Infancy Through Early Adolescence: A Moderated Nonlinear Factor Model
Authors: DeJoseph Meriah L. , Sifre Robin D. , Raver C. Cybele , Blair Clancy B. , Berry Daniel
Published: January 2021

Income, education, and cumulative‐risk indices likely obscure meaningful heterogeneity in the mechanisms through which poverty impacts child outcomes. This study draws from contemporary theory to specify multiple dimensions of poverty‐related adversity and resources, with the aim of better capturing these nuances. Using data from the Family Life Project (N = 1,292), we leveraged moderated nonlinear factor analysis (Bauer, 2017) to establish group‐ and longitudinally invariant environmental measures from infancy to early adolescence. Results indicated three latent factors—material deprivation, psychosocial threat, and sociocognitive resources—were distinct from each other and from family income. Each was largely invariant across site, racial group, and development and showed convergent and discriminant relations with age‐twelve criterion measures. Implications for ensuring socioculturally valid measurements of poverty are discussed.
Family ‘turning point’ experiences and the process of youth becoming homeless
Authors: Mayock Paula , Parker Sarah , Murphy Andrew
Published: January 2021

The role of family environments, where conflict—ranging from disagreements between young people and their parent(s) or carers to home‐based circumstances where violence and/or abuse is present—is well documented in research that has examined the causes and correlates of youth homelessness. However, far less attention has focused on how young people themselves frame and understand the significance of family ruptures. This paper examines the family ‘turning point’ experiences embedded in the life stories of homeless youth. The study, which was biographical and longitudinal, aimed to generate an in‐depth understanding of the nature of homelessness, how it emerged and its impacts on the lives of young people. Conducted in Ireland, 40 youth aged 16–24 years were recruited at baseline, with all interviews commencing with an invitation to young people to tell their ‘life story’. Analysis of participants' life story narratives revealed three major family turning point experiences associated withparental absence and separation,bereavementandacute interruptions to family life. These turning points, the effects of which had a temporal character, reveal the rippling impact of family ruptures on the lives of young people who embarked on a path of leaving home and becoming homeless. The implications of the findings for enhancing engagement with the families of young people who experience homelessness are discussed.
The performativity of surveys: Teenagers’ meaning‐making of the 'Health Behavior in School‐aged Children Survey' in Sweden
Authors: Wickström Anette , Zeiler Kristin
Published: January 2021

The Health Behaviour in School‐Aged Children survey contains scales intended to measure life satisfaction, mental health problems and socioeconomic status. This article takes inspiration from science and technology studies and analyse the survey as performative. It also examines subjective meaning‐making through an analysis of interviews with 15‐year‐old teenagers. It shows how the survey enacts the subject position of an accountable teenager and how teenagers experience the survey as sending a message about how one should live. While some teenagers experience this as positive, others narrate feelings of shame. This could be interpreted as a way for them to be accountable for themselves.
Emotion as a source of moral understanding in conservation
Authors: Batavia Chelsea , Nelson Michael Paul , Bruskotter Jeremy T. , Jones Megan S. , Yanco Esty , Ramp Daniel , Bekoff Marc , Wallach Arian D.
Published: January 2021

Recent debates around the meaning and implications of compassionate conservation suggest that some conservationists consider emotion a false and misleading basis for moral judgment and decision making. We trace these beliefs to a long‐standing, gendered sociocultural convention and argue that the disparagement of emotion as a source of moral understanding is both empirically and morally problematic. According to the current scientific and philosophical understanding, reason and emotion are better understood as partners, rather than opposites. Nonetheless, the two have historically been seen as separate, with reason elevated in association with masculinity and emotion (especially nurturing emotion) dismissed or delegitimated in association with femininity. These associations can be situated in a broader, dualistic, and hierarchical logic used to maintain power for a dominant male (White, able‐bodied, upper class, heterosexual) human class. We argue that emotion should be affirmed by conservationists for the novel and essential insights it contributes to conservation ethics. We consider the specific example of compassion and characterize it as an emotional experience of interdependence and shared vulnerability. This experience highlights conservationists’ responsibilities to individual beings, enhancing established and widely accepted beliefs that conservationists have a duty to protect populations, species, and ecosystems (or biodiversity). We argue compassion, thus understood, should be embraced as a core virtue of conservation.
Invader–pollinator paradox: Invasive goldenrods benefit from large size pollinators
Authors: Moroń Dawid , Marjańska Emilia , Skórka Piotr , Lenda Magdalena , Woyciechowski Michał
Published: January 2021

Aim

Mutualistic interactions between alien plants and native pollinators are needed to enable plant invasions. Although the increasing abundance of invasive plants in a habitat causes a dramatic decline of native pollinators, pollination services received by invaders are often sustained. This invader–pollinator paradox might be attributed to differences in pollination effectiveness and varying vulnerability to invasion among pollinators with different life history traits. In an experimental study, we explored the relationships between pollinator body size, pollination effectiveness and abundance of invasive species.

Location

Kraków area, Poland.

Methods

We placed a pair of potted invasive goldenrods (Solidago gigantea) at 25 sites differing in goldenrod abundance (cover: 0%–100%). Floral visitation rate of the potted goldenrods, as well as seed set and viability, was noted.

Results

Species richness of pollinators visiting inflorescences decreased with the increase of the goldenrod cover, whereas the floral visitation rate remained unchanged. However, the seed set was positively related to the goldenrod cover. Body size of floral visitors was structured along with the goldenrod cover so that pollinators' size increased with the cover. Also, the seed set of the potted plants, as well as goldenrod seed viability, depended positively on the body size of visiting pollinators.

Main conclusions

Invasive goldenrods did not suffer from pollinator shortage and ineffective pollination, especially in habitats densely covered by the invader, due to the presence of large‐bodied pollinators. Our study highlights that pollination and reproduction of invasive plants might be sustained through ecological filtering, affecting the composition of pollinators with traits increasing pollination effectiveness.
A role of Hey2 transcription factor for right ventricle development through regulation of Tbx2‐Mycn pathway during cardiac morphogenesis
Authors: Seya Daiki , Ihara Dai , Shirai Manabu , Kawamura Teruhisa , Watanabe Yusuke , Nakagawa Osamu
Published: January 2021

A basic helix‐loop‐helix transcription factor Hey2 is expressed in the ventricular myocardium and endocardium of mouse embryos, and Hey2 null mice die perinatally showing ventricular septal defect, dysplastic tricuspid valve and hypoplastic right ventricle. In order to understand region‐specific roles of Hey2 during cardiac morphogenesis, we generated Hey2 conditional knockout (cKO) mice using Mef2c‐AHF‐Cre, which was active in the anterior part of the second heart field and the right ventricle and outflow tract of the heart. Hey2 cKO neonates reproduced three anomalies commonly observed in Hey2 null mice. An earliest morphological defect was the lack of right ventricular extension along the apico‐basal axis at midgestational stages. Underdevelopment of the right ventricle was present in all cKO neonates including those without apparent atresia of right‐sided atrioventricular connection. RNA sequencing analysis of cKO embryos identified that the gene expression of a non‐chamber T‐box factor Tbx2 was ectopically induced in the chamber myocardium of the right ventricle. Consistently, mRNA expression of the Mycn transcription factor, which was a cell cycle regulator transcriptionally repressed by Tbx2, was down regulated, and the number of S‐phase cells was significantly decreased in the right ventricle of cKO heart. These results suggest that Hey2 plays an important role in right ventricle development during cardiac morphogenesis, at least in part, through mitigating Tbx2‐dependent inhibition of Mycn expression.
The early medieval secular: spectrum and strategies
Authors: O'Brien Conor
Published: January 2021

This special issue seeks to fill a gap by taking the first steps towards locating the early Middle Ages in the broader history of the secular. While it has generally been assumed that a division between religion and secular was impossible to make in the early medieval period, taken together the articles in this collection show a variety of early medieval seculars, all arising from a general assumption that distinctions could, indeed had to, be made between what was secular and what was not. The introduction proposes that scholars should think in terms of a spectrum of secularity; key to determining what sits within this spectrum must be the identification of secularizing strategies, i.e. attempts to draw a distinction between religious and secular in a particular context. Such an approach offers the possibility of a history of the secular that does not privilege one time or place.
After Augustine, after Markus: the problem of the secular at the end of antiquity
Authors: Whelan Robin
Published: January 2021

This article revisits Robert Markus's account of the de‐secularization of the Latin West between Augustine and Gregory the Great. It uses letters of advice for rulers written by early sixth‐century clerics to contest his narrative of a ‘grand simplification’ of Christian thought. Multiple overlapping conceptions of the secular were still in play after the fall of Rome, articulated, not in the absence of, but in dialogue with robust political institutions. By uncoupling Christian ideas of secularity from the actual degree of religious pluralism or tolerance in a given society, historians can better capture the continued complexity of early medieval secularities.