bluuebunny/crossref_metadata_2025 huggingface dataset:
Looking at the World Bank’s safeguard reform through the lens of deliberative democracy
Authors: Houghton Ruth
Published: June 2019

The sheer amount of non-state participation in the creation of the World Bank Environmental and Social Framework (ESF) is surely noteworthy. The aim of the Bank’s consultation was to get ‘global’ input and feedback, and with over 8,000 stakeholders from over 63 countries taking part, it is laudable. The extent of the participation challenges the positivist approach to international law-making, which views only states as having the power to make law and raises questions about how to legitimize such international soft-law making. Legitimacy is entangled with democracy, as scholars debate whether democracy is the required benchmark for decision-making processes at international organizations. This article uses deliberative democracy to analyse the ESF consultation process. Whilst, democratic legitimacy has been interpreted to mean inclusivity and participation, deliberative democracy raises a series of hard questions about equality and power that scholarship on global governance needs to grapple with. Although this participatory process at the World Bank challenges traditional narratives in international law, analysing it through a lens of deliberative democracy exposes the work that still needs to be done to discuss democracy in international decision-making.
Mechanisms of vitamin D action in skeletal muscle
Authors: Montenegro Karina Romeu , Cruzat Vinicius , Carlessi Rodrigo , Newsholme Philip
Published: June 2019

Vitamin D receptor expression and associated function have been reported in various muscle models, including C2C12, L6 cell lines and primary human skeletal muscle cells. It is believed that 1,25-hydroxyvitamin D3(1,25(OH)2D3), the active form of vitamin D, has a direct regulatory role in skeletal muscle function, where it participates in myogenesis, cell proliferation, differentiation, regulation of protein synthesis and mitochondrial metabolism through activation of various cellular signalling cascades, including the mitogen-activated protein kinase pathway(s). It has also been suggested that 1,25(OH)2D3and its associated receptor have genomic targets, resulting in regulation of gene expression, as well as non-genomic functions that can alter cellular behaviour through binding and modification of targets not directly associated with transcriptional regulation. The molecular mechanisms of vitamin D signalling, however, have not been fully clarified. Vitamin D inadequacy or deficiency is associated with muscle fibre atrophy, increased risk of chronic musculoskeletal pain, sarcopenia and associated falls, and may also decrease RMR. The main purpose of the present review is to describe the molecular role of vitamin D in skeletal muscle tissue function and metabolism, specifically in relation to proliferation, differentiation and protein synthesis processes. In addition, the present review also includes discussion of possible genomic and non-genomic pathways of vitamin D action.
The moderating effects of traumatic stress on vulnerability to emotional distress during pregnancy
Authors: Tung Irene , Keenan Kate , Stepp Stephanie D. , Hipwell Alison E.
Published: June 2019

Emotional distress during pregnancy is likely influenced by both maternal history of adversity and concurrent prenatal stressors, but prospective longitudinal studies are lacking. Guided by a life span model of pregnancy health and stress sensitization theories, this study investigated the influence of intimate partner violence (IPV) during pregnancy on the association between childhood adversity and prenatal emotional distress. Participants included an urban, community-based sample of 200 pregnant women (aged 18–24) assessed annually from ages 8 to 17 for a range of adversity domains, including traumatic violence, harsh parenting, caregiver loss, and compromised parenting. Models tested both linear and nonlinear effects of adversity as well as their interactions with IPV on prenatal anxiety and depression symptoms, controlling for potential confounds such as poverty and childhood anxiety and depression. Results showed that the associations between childhood adversity and pregnancy emotional distress were moderated by prenatal IPV, supporting a life span conceptualization of pregnancy health. Patterns of interactions were nonlinear, consistent with theories conceptualizing stress sensitization through an “adaptive calibration” lens. Furthermore, results diverged based on adversity subdomain and type of prenatal IPV (physical vs. emotional abuse). Findings are discussed in the context of existing stress sensitization theories and highlight important avenues for future research and practice.
Reducing childhood malnutrition in Bangladesh: the importance of addressing socio-economic inequalities
Authors: Islam Md Rashedul , Rahman Md Shafiur , Rahman Md Mahfuzur , Nomura Shuhei , de Silva Angela , Lanerolle Pulani , Jung Jenny , Rahman Md Mizanur
Published: June 2019

Objective:

To obtain projections of the prevalence of childhood malnutrition indicators up to 2030 and to analyse the changes of wealth-based inequality in malnutrition indicators and the degree of contribution of socio-economic determinants to the inequities in malnutrition indicators in Bangladesh. Additionally, to identify the risk factors of childhood malnutrition.

Design:

Cross-sectional study. A Bayesian linear regression model was used to estimate trends and projections of malnutrition. For equity analysis, slope index, relative index and decomposition in concentration index were used. Multilevel logistic models were used to identify risk factors of malnutrition.

Setting:

Household surveys in Bangladesh from 1996 to 2014.

Participants:

Children under the age of 5 years.

Results:

A decreasing trend was observed for all malnutrition indices. In 1990, predicted prevalence of stunting, wasting and underweight was 55·0, 15·9 and 61·8 %, respectively. By 2030, prevalence is projected to reduce to 28·8 % for stunting, 12·3 % for wasting and 17·4 % for underweight. Prevalence of stunting, wasting and underweight were 34·3, 6·9 and 32·8 percentage points lower in the richest households than the poorest households. Contribution of the wealth index to child malnutrition increased over time and the largest contribution of pro-poor inequity was explained by wealth index. Being an underweight mother, parents with a lower level of education and poorer households were the key risk factors for stunting and underweight.

Conclusions:

Our findings show an evidence-based need for targeted interventions to improve education and household income-generating activities among poor households to reduce inequalities and reduce the burden of child malnutrition in Bangladesh.
Cognitive Behavioural Therapy Suicide Prevention (CBT-SP) imagery intervention: a case report
Authors: Carey Marie , Wells Catherine
Published: June 2019

Very little clinical work or research to date has focused on the prioritization of suicidal imagery intervention in the stabilization of risk. Current Cognitive Behavioural Therapy Suicide Prevention (CBT-SP) does not specifically address suicidal imagery as a priority intervention. This paper prioritizes imagery modification as the central task of therapy with the suicidal client. This is a single subject case review describing specific imagery interventions used to destabilize the comforting component of suicidal images, de-glamourize the suicidal image as a problem-solving method and the reconstruction of new images to offset the emotional grasp of both ‘flash-forward’ violent suicidal images and suicidal ‘daydreaming’ rumination. It is hypothesized that when suicidal images become less emotionally charged, the desire to act upon suicide decreases. Focusing on imagery intervention as a priority aims to stabilize risk in a more clinically specific and targeted way. Rob is a 19-year-old depressed young man with chronic suicidal ideation/images with repeated suicide attempts. All GP referrals are of a crisis nature since the age of 16. He was referred to a CBT clinician with specific training and experience in CBT-SP who proposed the following brief imagery intervention. Socialization to treatment rationale was pivotal at the outset to help facilitate strong therapeutic alliance, ‘buy-in’ to the intended de-glamourization of suicide planning/daydreaming/rumination and the effects of intrusive ‘flash-forward’ images on emotional well-being. Therapy was facilitated weekly, supported by telephone contact, on an out-patient basis in the HSE (Health Service Executive) Irish Adult Mental Health service. The care plan and interventions were supported by access to the 24-hour acute Adult Mental Health services, as required. There was no requirement for direct client engagement with the acute services. Rob engaged with five treatments of CBT-SP imagery intervention and full stabilization of risk to self by suicide was achieved. At the time of writing, Rob is alive, has no engagement with the services and no further GP referral requests for intervention. Despite Rob leaving therapy before full completion, brief targeted suicidal imagery intervention was observed to stabilize the risk of suicidal behaviour. This young man has completed his schooling, engaged in ‘life’ planning rather than ‘death’ planning and has not required further intervention from this service. Further research is required to engage frontline clinicians on the merits of suicidal imagery assessment in routine clinical practice.

Key learning aims

(1)

To assess for imagery and violent day dreaming in suicidal patients.

(2)

Conceptualizing suicidal rumination and daydreaming as being a maladaptive problem-solving technique in overcoming psychological pain.

(3)

Use of suicide-specific assessment.

(4)

Ask about the presence of suicidal imagery as part of routine mental health assessment with the suicidal client.
The Secular-Religious Competition Perspective in Comparative Perspective
Authors: Fox Jonathan
Published: June 2019

Political secularism is defined as “an ideology or set of beliefs advocating that religion ought to be separate from all or some aspects of politics or public life (or both).” In thesecular–religious competition perspective, I argue that political secularists compete with religious political actors to influence government policy around the world. Yet this competition is complicated by many factors. The contributions to this symposium demonstrate that this is the case in their examination of secular–religious tensions and state–religion relations in Denmark, the Netherlands, Germany, Italy, Turkey, and Tunisia. These cases show that government religion policy evolves over time and is deeply influenced by secular–religious competition but that this competition is a complex one involving many other factors and influences.
Rethinking political distrust
Authors: Bertsou Eri
Published: June 2019

Increasing political distrust has become a commonplace observational remark across many established democracies, and it is often used to explain current political phenomena. In contrast to most scholarship that focuses solely on the concept of trust and leaves distrust untheorized, this article makes a contribution by analysing political distrust. It argues that citizen distrust of government and political institutions poses a threat for democratic politics and clarifies the relationship between the distrust observed in established democracies and classical ‘liberal distrust’, which is considered beneficial for democracy. Further, it addresses the relationship between trust and distrust, identifying a series of functional asymmetries between the two concepts, with important implications for theoretical and empirical work in political science. The article suggests that a conceptualization of political distrust based on evaluations of incompetence, unethical conduct and incongruent interests can provide a fruitful ground for future research that aims to understand the causes, consequences, and potential remedies for political distrust.
Maternal physical activity-induced adaptive transcriptional response in brain and placenta of mothers and rat offspring
Authors: Fragoso Jéssica , Carvalho Jurema Santos Gabriela , Thomaz da Silva Helyson , Oliveira Nogueira Viviane , Loizon Emmanuelle , Vidal Hubert , Costa-Silva João Henrique , da Silva Aragão Raquel , Pirola Luciano , Leandro Carol Gois
Published: June 2019

Maternal physical activity induces brain functional changes and neuroplasticity, leading to an improvement of cognitive functions, such as learning and memory in the offspring. This study investigated the effects of voluntary maternal physical activity on the gene expression of the neurotrophic factors (NTFs): BDNF, NTF4, NTRK2, IGF-1 and IGF-1r in the different areas of mother’s brain, placenta and foetus brain of rats. Female Wistar rats (n = 15) were individually housed in voluntary physical activity cages, containing a running wheel, for 4 weeks (period of adaptation) before gestation. Rats were classified as inactive (I, n = 6); active (A, n = 4) and very active (VA, n = 5) according to daily distance spontaneously travelled. During gestation, the dams continued to have access to the running wheel. At the 20th day of gestation, gene expression of NTFs was analysed in different areas of mother’s brain (cerebellum, hypothalamus, hippocampus and cortex), placenta and the offspring’s brain. NTFs gene expression was evaluated using quantitative PCR. Very active mothers showed upregulation of IGF-1 mRNA in the cerebellum (36.8%) and NTF4 mRNA expression in the placenta (24.3%). In the cortex, there was a tendency of up-regulation of NTRK2 mRNA (p = 0.06) in the A and VA groups when compared to I group. There were no noticeable changes in the gene expression of NTFs in the offspring’s brain. Our findings suggest the existence of a developmental plasticity induced by maternal physical activity in specific areas of the brain and placenta representing the first investment for offspring during development.
Sleep Disorders and Risk of Incident Depression: A Population Case–Control Study
Authors: Byrne Enda M. , Timmerman Allan , Wray Naomi R. , Agerbo Esben
Published: June 2019

We sought to investigate the risk of incident major depressive disorder (MDD) attributable to a range of sleep disorders in the Danish population. Data were obtained by linking longitudinal Danish population-based registers. A total of 65,739 individuals who had first onset of depression between 1995 and 2013 were selected as cases. For each case, a set of 20 controls of the same sex, birth month and year and who had not had depression by the date that the case was diagnosed were selected at random form the population (N = 1,307,580 in total). We examined whether there was an increased rate of prior sleep disorders in MDD cases compared to controls using conditional logistic regression. An increased risk of incident depression in cases was found for all sleep disorders analyzed. Highest incidence rate ratios (IRRs) were found for circadian rhythm disorders (IRR = 7.06 [2.78–17.91]) and insomnia of inorganic origin (IRR = 6.76 [4.37–10.46]). The lowest estimated IRR was for narcolepsy (IRR = 2.00 [1.26–3.17]). Those diagnosed with a sleep disorder in the last 6 months were at highest risk of developing depression compared to those with at least 1 year since diagnosis (3.10 vs. 2.36). Our results suggest that having any sleep disorder is a risk factor for incident depression. Depression screening should be considered for patients with sleep disorders, and where possible, long-term follow-up for mental health problems is advisable.
Lives Lived in “Someone Else's Hands”: Precarity and Profit-making of Migrants and Left-behind Children in the Philippines
Authors: Alipio Cheryll
Published: June 2019

In the labour brokerage state of systematic recruitment and export for the maximisation of labour, development, and profit, the Philippines continues to simultaneously fashion migrant workers as temporary, yet heroic and sacrificial. As the largest migrant-sending country in Southeast Asia and the third largest remittance recipient in Asia, the Philippines’ discourse of migrants as modern-day heroes and martyrs reveals the interplay of nationalist myths and cultural values, alongside the neoliberal favouring of finance and flexible labour, to craft filial migrants and celebrate mobile, capitalist subjects over migrants’ welfare and well-being. The article explores the contemporaneous institutionalisation of migrant labour and migrants’ institutionalised uncertainty lived every day to investigate how this profound precariousness in the Philippines is perpetuated historically to shape the resilience and realities of migrants and their left-behind children today. Drawing from news reports and films on migrant lives and ethnographic fieldwork in the Philippines, this article considers how the formation and deployment of overseas Filipino workers (OFWs) turns from a focus on sustaining the nation to supporting migrant families and developing translocal communities. Through this examination, the paper seeks to uncover who profits and is indebted from the precarity created and sustained by the larger economic system built on transnational labour migration.
Intracloud Lightning Flashes Initiated at High Altitudes and Dominated by Downward Positive Leaders
Authors: Wu Ting , Wang Daohong , Takagi Nobuyuki
Published: June 2019

Intracloud (IC) lightning flashes are normally initiated below 10 km and start with upward negative leaders. In this paper, we report a special type of IC flash called “downward positive IC (+IC) flash” which is initiated at high altitudes (mainly above 12 km) and whose initial negative leaders do not propagate upward. Three‐dimensional location results of three downward +IC flashes are described in detail. It is demonstrated that downward +IC flashes start with positive leaders propagating downward with speeds on the order of 104 m/s and negative leaders propagating horizontally for only a short distance. Downward +IC flashes are produced in thunderstorms with deep convective updrafts (radar echoes of cloud tops typically higher than 14 km). The charge structure responsible for downward +IC flashes is inferred to be a positive dipole including a negative charge region at a normal altitude (near the −10 °C isotherm) and an upper positive charge region at a relatively high altitude (usually above the −50 °C isotherm), with downward +IC flashes likely initiated from the upper positive charge region. Further, lightning flashes in a thunderstorm producing a large number of downward +IC flashes are analyzed. Results show that normal IC flashes in this thunderstorm are also initiated at altitudes closer to the upper positive charge region and usually consist of downward positive leaders propagating for longer distances than upward negative leaders. Based on these results, we propose a relationship between the altitude of the upper positive charge region and initiation locations of IC flashes.
A Regional Scale‐Invariant Extreme Value Model of Rainfall Intensity‐Duration‐Area‐Frequency Relationships
Authors: Mélèse Victor , Blanchet Juliette , Creutin Jean‐Dominique
Published: June 2019

We propose in this article a regional study of intensity‐duration‐area‐frequency (IDAF) relationships of annual rainfall maxima in southern France. For this we develop a regional extreme value IDAF model based on space‐time scale invariance hypotheses. The model allows us to link the statistical distributions of rainfall maxima over any duration and area. It provides in particular an analytical expression of the areal reduction factor, which expresses how the statistical distribution of rainfall maxima changes as the area increases, for any fixed duration. It also provides an analytical expression of areal return level for the continuum of area and duration. The model is applied to radar reanalysis data covering a 13,000‐km2 region of southern France featuring contrasted rainfall regimes (2008–2015). We estimate the IDAF relationships centered on any radar pixel of the region in the range 3–48 hr and 1–2,025 km2. We obtain in particular a spatial distribution of the areal reduction factor, which allows us to distinguish different rainfall regimes in the region. The overall IDAF model provides also a regional quantification of areal rainfall risk by allowing the computation of rainfall return level maps for any area and duration in the applicable range. Despite inevitable sampling issues due to the shortness of the data sample, we highlight important differences in the spatial distribution of areal rainfall risk depending on the area and duration, illustrating that a comprehensive storm risk evaluation should consider the continuum of area and duration rather than arbitrarily predefined ones.
RETRACTED ARTICLE: Caveolin-1 promotes invasion and metastasis by upregulating Pofut1 expression in mouse hepatocellular carcinoma
Authors: Zhang Cheng , Huang Huang , Zhang Junshi , Wu Qiong , Chen Xixi , Huang Tianmiao , Li Wenli , Liu Yubo , Zhang Jianing
Published: June 2019

Caveolin-1 (Cav-1) is an important structural protein of caveolae and plays an oncogene-like role by influencing protein glycosylation in hepatocellular carcinoma (HCC) cells. However, the mechanism by which Cav-1 promotes invasion and metastasis capacity has not been completely clarified. In this study, we demonstrate that Pofut1 is a fucosyltransferase induced by Cav-1. Mouse Hepa1-6 HCC cells lacking Cav-1 expression exhibited low transcription levels of Pofut1, whereas strong Pofut1 expression was found in high-metastasis-potential Hca-F cells with high levels of Cav-1. Cav-1 activated MAPK signaling and promoted phosphorylation of the transcription factors CREB, Sp1, HNF4A and c-Myc, which bound to the Pofut1 promoter region to induce its transcription. As Notch signaling receptors can be modified with O-fucose by Pofut1, we further showed that Cav-1-induced upregulation of Pofut1 expression activated the Notch pathway and thus enhanced invasion and metastasis by mouse HCC cells in vitro and in vivo. Collectively, our findings reveal a novel mechanism by which Cav-1 promotes tumor metastasis by upregulating expression of Pofut1, suggesting that Cav-1 may function as a new biomarker for HCC.
miR-665 expression predicts poor survival and promotes tumor metastasis by targeting NR4A3 in breast cancer
Authors: Zhao Xin-Ge , Hu Jing-Ye , Tang Jun , Yi Wei , Zhang Mei-Yin , Deng Rong , Mai Shi-Juan , Weng Nuo-Qing , Wang Rui-Qi , Liu Ji , Zhang Hui-Zhong , He Jie-Hua , Wang Hui-Yun
Published: June 2019

Cancer metastasis is the main cause of death in breast cancer (BC) patients. Therefore, prediction and treatment of metastasis is critical for enhancing the survival of BC patients. In this study, we aimed to identify biomarkers that can predict metastasis of BC and elucidate the underlying mechanism of the functional involvement of such markers in metastasis. miRNA expression profile was analyzed using a custom microarray system in 422 BC tissues. The relationship between the upregulated miR-665, metastasis and survival of BC was analyzed and verified in another set of 161 BC samples. The biological function of miR-665 in BC carcinogenesis was explored with in vitro and in vivo methods. The target gene of miR-665 and its signaling cascade were also analyzed. There are 399 differentially expressed miRNAs between BC and noncancerous tissues, of which miR-665 is the most upregulated miRNA in the BC tissues compared with non-tumor breast tissues (P < 0.001). The expression of miR-665 predicts metastasis and poor survival in 422 BC patients, which is verified in another 161 BC patients and 2323 BC cases from online databases. Ectopic miR-665 expression promotes epithelial–mesenchymal transition (EMT), proliferation, migration and invasion of BC cells, and increases tumor growth and metastasis of BC in mice. Bioinformatics, luciferase assay and other methods showed that nuclear receptor subfamily 4 group A member 3 (NR4A3) is a target of miR-665 in BC. Mechanistically, we demonstrated that miR-665 promotes EMT, invasion and metastasis of BC via inhibiting NR4A3 to activate MAPK/ERK kinase (MEK) signaling pathway. Our study demonstrates that miR-665 upregulation is associated with metastasis and poor survival in BC patients, and mechanistically, miR-665 enhances progression of BC via NR4A3/MEK signaling pathway. This study provides a new potential prognostic biomarker and therapeutic target for BC patients.
TLR9 is essential for HMGB1-mediated post-myocardial infarction tissue repair through affecting apoptosis, cardiac healing, and angiogenesis
Authors: Liu Fang-Yuan , Fan Di , Yang Zheng , Tang Nan , Guo Zhen , Ma Shu-Qing , Ma Zhen-Guo , Wu Hai-Ming , Deng Wei , Tang Qi-Zhu
Published: June 2019

The poor prognosis of patients with acute myocardial infarction is partially attributed to a large number of cardiomyocyte apoptosis, necrosis, limited cardiac healing and angiogenesis, and cardiac dysfunction. Immune cells dysfunction leads to nonhealing or poor healing of wounds after acute myocardial infarction. Toll-like receptor 9 (TLR9) as an essential part of the innate immune system plays a vital role in regulating cardiomyocyte survival and wound healing. During hypoxia, High Mobility Group Box 1 (HMGB1), as the typical damage-associated molecular patterns (DAMPs) or alarmin, is rapidly released extracellularly and translocates from the nucleus to bind with cytoplasmic TLR9. However, the mechanism by which TLR9 interacts with HMGB1 and regulates myocardial damage remains unclear. Our current study found that the survival rate of TLR9KO mice with a higher rate of cardiac rupture was significantly lower than that in WT mice after 28 days post-operation. The effect of TLR9 knockout on insufficient wound healing in experimental MI was caused by a diminished number of myofibroblast and defective matrix synthetic capability. Moreover, the increased myocardial apoptotic cells and decreased angiogenic capacity were found in TLR9 knockout mice after MI. The results showed contrary in Recombinant Human High Mobility Group Box 1 (rhHMGB1) treated WT mice and similarity after applying rhHMGB1 in TLR9KO mice. This study demonstrates that TLR9 is essential for the repair of infarcted myocardium and interaction of HMGB1 and TLR9 is involved in the survival of myocardial cells, wound healing, and angiogenesis after myocardial infarction.
BRCA2 deficiency is a potential driver for human primary ovarian insufficiency
Authors: Miao Yilong , Wang Pan , Xie Bingteng , Yang Mo , Li Sen , Cui Zhaokang , Fan Yong , Li Mo , Xiong Bo
Published: June 2019

Reproductive problem has been one of the top issues for women health worldwide in recent decades. As a typical female disease, primary ovarian insufficiency (POI) results in a loss of ovarian follicles and oocytes that thus destroys women fertility. However, due to the complex of POI etiology and rare resource of human POI oocytes, few biomarkers have been identified in clinics and no effective strategy could be applied to treat POI patients. In the search of possible association between DNA damage and POI by Smart-Seq2 and RT2profiler PCR array, we find thatBRCA2, a core DNA repair gene for homologous recombination shows significantly lower expression in two POI patient oocytes. In line with this, we generated oocyte-specific knockout mouse model driven byGdf9-Cre. TheBrca2-deficient mice are infertile because of the arrested follicle development and defective oocyte quality caused by the accumulation of DNA damage. Notably, ectopic expression of Brca2 inBrca2-deficient oocytes could partially restore the oocyte maturation and chromosome stability. Collectively, our data assign a definite deficiency toBRCA2as a POI driver during follicle development and oocyte maturation, and provide a potential fertility treatment strategy for POI patients induced byBRCA2deficiency.
Design and application of α-ketothioesters as 1,2-dicarbonyl-forming reagents
Authors: Wang Ming , Dai Zhihong , Jiang Xuefeng
Published: June 2019

The 1,2-dicarbonyl motif is vital to biomolecules, especially natural products and pharmaceuticals. Conventionally, 1,2-dicarbonyl compounds are prepared via an α-keto acyl chloride. Based on the methods used in nature, a transition-metal-free approach for the synthesis of an α-ketothioester reagent via the combination of an α-hydroxyl ketone, elemental sulfur and a benzyl halide is reported. Mechanistic studies demonstrate that the trisulfur radical anion and the α-carbon radical of the α-hydroxy ketone are involved in this transformation. The dicarbonylation of a broad range of amines and amino acids, and importantly, cross couplings with aryl borates to construct dicarbonyl-carbon bonds are realized under mild conditions by employing this stable and convenient α-ketothioester as a 1,2-dicarbonyl reagent. The dicarbonyl-containing drug indibulin and the natural product polyandrocarpamide C, which possess multiple heteroatoms and active hydrogen functional groups, can be efficiently prepared using the designed 1,2-dicarbonyl reagent.
Single-defect spectroscopy in the shortwave infrared
Authors: Wu Xiaojian , Kim Mijin , Qu Haoran , Wang YuHuang
Published: June 2019

Chemical defects that fluoresce in the shortwave infrared open exciting opportunities in deep-penetration bioimaging, chemically specific sensing, and quantum technologies. However, the atomic size of defects and the high noise of infrared detectors have posed significant challenges to the studies of these unique emitters. Here we demonstrate high throughput single-defect spectroscopy in the shortwave infrared capable of quantitatively and spectrally resolving chemical defects at the single defect level. By cooling an InGaAs detector array down to −190 °C and implementing a nondestructive readout scheme, we are able to capture low light fluorescent events in the shortwave infrared with a signal-to-noise ratio improved by more than three orders-of-magnitude. As a demonstration, we show it is possible to resolve individual chemical defects in carbon nanotube semiconductors, simultaneously collecting a full spectrum for each defect within the entire field of view at the single defect limit.
Bilateral international migration flow estimates for 200 countries
Authors: Abel Guy J. , Cohen Joel E.
Published: June 2019

Data on stocks and flows of international migration are necessary to understand migrant patterns and trends and to monitor and evaluate migration-relevant international development agendas. Many countries do not publish data on bilateral migration flows. At least six methods have been proposed recently to estimate bilateral migration flows between all origin-destination country pairs based on migrant stock data published by the World Bank and United Nations. We apply each of these methods to the latest available stock data to provide six estimates of five-year bilateral migration flows between 1990 and 2015. To assess the resulting estimates, we correlate estimates of six migration measures from each method with equivalent reported data where possible. Such systematic efforts at validation have largely been neglected thus far. We show that the correlation between the reported data and the estimates varies widely among different migration measures, over space, and over time. We find that the two methods using a closed demographic accounting approach perform consistently better than the four other estimation approaches.
Multiplex RNA single molecule FISH of inducible mRNAs in single yeast cells
Authors: Li Guoliang , Neuert Gregor
Published: June 2019

Transcript levels powerfully influence cell behavior and phenotype and are carefully regulated at several steps. Recently developed single cell approaches such as RNA single molecule fluorescence in-situ hybridization (smFISH) have produced advances in our understanding of how these steps work within the cell. In comparison to single-cell sequencing, smFISH provides more accurate quantification of RNA levels. Additionally, transcript subcellular localization is directly visualized, enabling the analysis of transcription (initiation and elongation), RNA export and degradation. As part of our efforts to investigate how this type of analysis can generate improved models of gene expression, we used smFISH to quantify the kinetic expression of STL1 and CTT1 mRNAs in single Saccharomyces cerevisiae cells upon 0.2 and 0.4 M NaCl osmotic stress. In this Data Descriptor, we outline our procedure along with our data in the form of raw images and processed mRNA counts. We discuss how these data can be used to develop single cell modelling approaches, to study fundamental processes in transcription regulation and develop single cell image processing approaches.
Early human settlement of Sahul was not an accident
Authors: Bird Michael I. , Condie Scott A. , O’Connor Sue , O’Grady Damien , Reepmeyer Christian , Ulm Sean , Zega Mojca , Saltré Frédérik , Bradshaw Corey J. A.
Published: June 2019

The first peopling of Sahul (Australia, New Guinea and the Aru Islands joined at lower sea levels) by anatomically modern humans required multiple maritime crossings through Wallacea, with at least one approaching 100 km. Whether these crossings were accidental or intentional is unknown. Using coastal-viewshed analysis and ocean drift modelling combined with population projections, we show that the probability of randomly reaching Sahul by any route is <5% until ≥40 adults are ‘washed off’ an island at least once every 20 years. We then demonstrate that choosing a time of departure and making minimal headway (0.5 knots) toward a destination greatly increases the likelihood of arrival. While drift modelling demonstrates the existence of ‘bottleneck’ crossings on all routes, arrival via New Guinea is more likely than via northwestern Australia. We conclude that anatomically modern humans had the capacity to plan and make open-sea voyages lasting several days by at least 50,000 years ago.
Author Correction: Differences in the fecal microbiota of neonates born at home or in the hospital
Authors: Combellick Joan L. , Shin Hakdong , Shin Dongjae , Cai Yi , Hagan Holly , Lacher Corey , Lin Din L. , McCauley Kathryn , Lynch Susan V. , Dominguez-Bello Maria Gloria
Published: June 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Oxylipins in triglyceride-rich lipoproteins of dyslipidemic subjects promote endothelial inflammation following a high fat meal
Authors: Rajamani Anita , Borkowski Kamil , Akre Samir , Fernandez Andrea , Newman John W. , Simon Scott I. , Passerini Anthony G.
Published: June 2019

Elevated triglyceride-rich lipoproteins (TGRL) in circulation is a risk factor for atherosclerosis. TGRL from subjects consuming a high saturated fat test meal elicited a variable inflammatory response in TNFα-stimulated endothelial cells (EC) that correlated strongly with the polyunsaturated fatty acid (PUFA) content. This study investigates how the relative abundance of oxygenated metabolites of PUFA, oxylipins, is altered in TGRL postprandially, and how these changes promote endothelial inflammation. Human aortic EC were stimulated with TNFα and treated with TGRL, isolated from subjects’ plasma at fasting and 3.5 hrs postprandial to a test meal high in saturated fat. Endothelial VCAM-1 surface expression stimulated by TNFα provided a readout for atherogenic inflammation. Concentrations of esterified and non-esterified fatty acids and oxylipins in TGRL were quantified by mass spectrometry. Dyslipidemic subjects produced TGRL that increased endothelial VCAM-1 expression by ≥35%, and exhibited impaired fasting lipogenesis activity and a shift in soluble epoxide hydrolase and lipoxygenase activity. Pro-atherogenic TGRL were enriched in eicosapentaenoic acid metabolites and depleted in esterified C18-PUFA-derived diols. Abundance of these metabolites was strongly predictive of VCAM-1 expression. We conclude the altered metabolism in dyslipidemic subjects produces TGRL with a unique oxylipin signature that promotes a pro-atherogenic endothelial phenotype.
Upconverting SrF2 nanoparticles doped with Yb3+/Ho3+, Yb3+/Er3+ and Yb3+/Tm3+ ions – optimisation of synthesis method, structural, spectroscopic and cytotoxicity studies
Authors: Przybylska Dominika , Ekner-Grzyb Anna , Grześkowiak Bartosz F. , Grzyb Tomasz
Published: June 2019

For a number of years nanomaterials have been continuously devised and comprehensively investigated because of the growing demand for them and their multifarious applications, especially in medicine. This paper reports on the properties of SrF2 nanoparticles (NPs) for applications in biomedicine, showing effective ways of their synthesis and luminescence under near infrared radiation - upconversion. NPs doped with lanthanide, Ln3+ ions (where Ln = Yb, Ho, Er, Tm) were prepared by the hydrothermal method and subjected to comprehensive studies, from determination of their structure and morphology, revealing small, 15 nm structures, through spectroscopic properties, to cytotoxicity in vitro. The effects of such factors as the reaction time, type and amount of precipitating compounds and complexing agents on the properties of products were characterized. The cytotoxicity of the synthesized and functionalized NPs was investigated, using human fibroblast cell line (MSU-1.1). The synthesized structures may decrease cells’ proliferation in a dose-dependent manner in the measured concentration range (up to 100 µg/mL). However, the cells remain alive according to the fluorescent assay. Moreover, the treated cells were imaged using confocal laser scanning microscopy. Cellular uptake was confirmed by the presence of upconversion luminescence in the cells.
Adipose Tissue Mast Cells Promote Human Adipose Beiging in Response to Cold
Authors: Finlin Brian S. , Confides Amy L. , Zhu Beibei , Boulanger Mary C. , Memetimin Hasiyet , Taylor Kyle W. , Johnson Zachary R. , Westgate Philip M. , Dupont-Versteegden Esther E. , Kern Philip A.
Published: June 2019

In a recent study, repeated cold application induced beiging in subcutaneous white adipose tissue (SC WAT) of humans independent of body mass index. To identify factors that promote or inhibit beiging, we performed multiplex analysis of gene expression with the Nanostring nCounter system (the probe set contained genes for specific immune cell markers, cytokines, and chemokines) on the SC WAT from lean subjects. Multiple correlations analysis identified mast cell tryptase and CCL26, a chemokine for mast cells, as genes whose change correlated positively with the change in UCP1 in SC WAT, leading to the hypothesis that mast cells promote SC WAT beiging in response to cold. We quantified mast cell recruitment into SC WAT and degranulation. Mast cells increased in number in SC WAT in lean subjects, and there was an increase in the number of degranulated mast cells in both lean subjects and subjects with obesity. We determined that norepinephrine stimulated mast cell degranulation and histamine release in vitro. In conclusion, cold stimulated adipose tissue mast cell recruitment in lean subjects and mast cell degranulation in SC WAT of all research participants independent of baseline body mass index, suggesting that mast cells promote adipose beiging through the release of histamine or other products.
Real-time magnetic resonance imaging – guided coronary intervention in a porcine model
Authors: Heidt Timo , Reiss Simon , Krafft Axel J. , Özen Ali Caglar , Lottner Thomas , Hehrlein Christoph , Galmbacher Roland , Kayser Gian , Hilgendorf Ingo , Stachon Peter , Wolf Dennis , Zirlik Andreas , Düring Klaus , Zehender Manfred , Meckel Stephan , von Elverfeldt Dominik , Bode Christoph , Bock Michael , von zur Mühlen Constantin
Published: June 2019

X-ray fluoroscopy is the gold standard for coronary diagnostics and intervention. Magnetic resonance imaging is a radiation-free alternative to x-ray with excellent soft tissue contrast in arbitrary slice orientation. Here, we assessed real-time MRI-guided coronary interventions from femoral access using newly designed MRI technologies. Six Goettingen minipigs were used to investigate coronary intervention using real-time MRI. Catheters were custom-designed and equipped with an active receive tip-coil to improve visibility and navigation capabilities. Using modified standard clinical 5 F catheters, intubation of the left coronary ostium was successful in all animals. For the purpose of MR-guided coronary interventions, a custom-designed 8 F catheter was used. In spite of the large catheter size, and therefore limited steerability, intubation of the left coronary ostium was successful in 3 of 6 animals within seconds. Thereafter, real-time guided implantation of a non-metallic vascular scaffold into coronary arteries was possible. This study demonstrates that real-time MRI-guided coronary catheterization and intervention via femoral access is possible without the use of any contrast agents or radiation, including placement of non-metallic vascular scaffolds into coronary arteries. Further development, especially in catheter and guidewire technology, will be required to drive forward routine MR-guided coronary interventions as an alternative to x-ray fluoroscopy.
Short exposure to cold atmospheric plasma induces senescence in human skin fibroblasts and adipose mesenchymal stromal cells
Authors: Bourdens Marion , Jeanson Yannick , Taurand Marion , Juin Noémie , Carrière Audrey , Clément Franck , Casteilla Louis , Bulteau Anne-Laure , Planat-Bénard Valérie
Published: June 2019

Cold Atmospheric Plasma (CAP) is a novel promising tool developed in several biomedical applications such as cutaneous wound healing or skin cancer. Nevertheless, in vitro studies are lacking regarding to CAP effects on cellular actors involved in healthy skin healing and regarding to the mechanism of action. In this study, we investigated the effect of a 3 minutes exposure to CAP-Helium on human dermal fibroblasts and Adipose-derived Stromal Cells (ASC) obtained from the same tissue sample. We observed that CAP treatment did not induce cell death but lead to proliferation arrest with an increase in p53/p21 and DNA damages. Interestingly we showed that CAP treated dermal fibroblasts and ASC developed a senescence phenotype with p16 expression, characteristic morphological changes, Senescence-Associated β-galactosidase expression and the secretion of pro-inflammatory cytokines defined as the Senescence-Associated Secretory Phenotype (SASP). Moreover this senescence phenotype is associated with a glycolytic switch and an increase in mitochondria content. Despite this senescence phenotype, cells kept in vitro functional properties like differentiation potential and immunomodulatory effects. To conclude, we demonstrated that two main skin cellular actors are resistant to cell death but develop a senescence phenotype while maintaining some functional characteristics after 3 minutes of CAP-Helium treatment in vitro.
Contribution of DNA methylation to the expression of FCGRT in human liver and myocardium
Authors: Cejas R. B. , Ferguson D. C. , Quiñones-Lombraña A. , Bard J. E. , Blanco J. G.
Published: June 2019

FcRn mediates recycling and transcytosis of IgG and albumin in various cell types. The MHC-class-I-like protein of the FcRn heterodimer is encoded by FCGRT. Few determinants of variable FCGRT expression in humans have been identified so far. In this study, we investigated the presence of DNA methylation in regulatory regions of FCGRT in samples of human liver and myocardium tissue, and we examined the impact of FCGRT methylation on FcRn expression in model cell lines. Quantitative DNA methylation analysis of the FCGRT locus revealed differentially methylated regions in DNA from liver and myocardium. Methylation status in individual CpG sites correlated with FCGRT mRNA expression. Data from model cell lines suggest that differential methylation in the −1058 to −587 bp regulatory region of FCGRT contributes to FcRn expression. Chromatin immunoprecipitation assays indicate that CpG site methylation impacts the binding of the methylation sensitive transcription factors Zbtb7a and Sp1. This study provides a foundation to further define the contribution of epigenetic factors during the control of FcRn expression and IgG traffic in human tissues.
Prenatal diagnosis of hypospadias with 2-dimensional and 3-dimensional ultrasonography
Authors: Li Xiaohua , Liu Aqing , Zhang Zhonglu , An Xia , Wang Shaochun
Published: June 2019

To compare the prenatal diagnostic performance as well as appearance of ultrasonic details between 2-dimensional ultrasonography (2DUS) combined with 3-dimensional ultrasonography (3DUS) and 2DUS alone for hypospadias. A total of 47 fetuses were enrolled and examined by 2DUS and then 3DUS. Postnatal follow-up data were obtained and 28 cases were confirmed of hypospadias. Although not statistically significant, there was a trend toward higher AUC (0.85 vs. 0.76; p = 0.08), ACC (85.1 vs. 76.6%; p = 0.22), SEN (85.7 vs. 78.6%; p = 0.63), and SPE (84.2 vs. 73.7%; p = 0.50) for 2DUS combined with 3DUS compared with 2DUS alone. The agreement between both methods was moderate [kappa = 0.592]. Both modalities showed accurately the short penis and blunt tip of the penis. 2DUS in combination with 3DUS showed more cases in other detailed features, such as “chordee”, a “hooded” incomplete prepuce, and so on. Overall 2DUS combined with 3DUS showed a trend toward higher performance compared with 2DUS alone for the diagnosis of hypospadias, although the difference was not statistically significant. 3DUS is a useful complement for 2DUS in the diagnosis of fetal hypospadias and may provide more detailed information related to its diagnosis and prognosis.
Depletion of Intestinal Microbiome Partially Rescues Bone Loss in Sickle Cell Disease Male Mice
Authors: Tavakoli Sara , Xiao Liping
Published: June 2019

Osteoporosis or osteopenia are common clinical manifestations of sickle cell disease (SCD) with unclear mechanisms. Since senescence of circulating neutrophil can be modulated by signals derived from intestinal microbiome and neutrophils are abundant in bone marrow and can regulate osteoblasts and osteoclasts, we examined whether gut microbiome contributes to bone loss in SCD mice. SCD and their littermates control mice were treated with antibiotics to deplete gut microbiome. At the end of 7 weeks treatment, serum was collected for biochemistry marker measurements. Bone mass and remodeling were evaluated by dual beam X-ray absorptiometry, micro-computed tomography, and histomorphometry. Bone-related genes in tibia and barrier marker genes in the small intestine were analyzed by quantitative PCR. Antibiotic treatment rescued increased intestinal inflammatory cytokine marker genes (Tnfα,IL17,Ifnγ) expression, rescued decreased intestinal barrier marker genes (claudin 3andclaudin 15) expression, and rescued increased serum cytokines (IFNγ, IL27, IL10) in SCD mice. Antibiotic significantly improved decreased bone mass in SCD mice mainly through enhanced osteoblast function and increased osteoblast-related genes (Runx2andIgf1) expression in SCD mice. Our findings support that increased bacteria load augments antigenic load traversing the impaired intestinal barrier through inflammation, leading to increased inflammatory cytokines, impaired osteoblast function, and bone loss in SCD mice.