bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and Social Determinants of Health in Asthma in Developed Economies: a Scoping Review of Literature Published Between 2014 and 2019
Authors: Sullivan Kathryn , Thakur Neeta
Published: February 2020

Purpose of Review

Using the WHO Conceptual Framework for Action on the Social Determinants of Health, this review provides a discussion of recent epidemiologic, mechanistic, and intervention studies of structural and social determinants of health and asthma outcomes covering the period from 2014 to 2019.

Recent Findings

A majority of studies and interventions to date focus on the intermediary determinants of health (e.g., housing), which as the name suggests, exist between the patient and the upstream structural determinants of health (e.g., housing policy). Race/ethnicity remains a profound social driver of asthma disparities with cumulative risk from many overlapping determinants. A growing number of studies on asthma are beginning to elucidate the underlying mechanisms that connect social determinants to human disease. Several effective interventions have been developed, though a need for large-scale policy research and innovation remains.

Strong evidence supports the key role of the structural determinants, which generate social stratification and inequity, in the development and progression of asthma; yet, interventions in this realm are challenging to develop and therefore infrequent. Proximal, intermediary determinants have provided a natural starting point for interventions, though structural interventions have the most potential for major impact on asthma outcomes. Further research to investigate the interactive effect of multiple determinants, as well as intervention studies, specifically those that are cross-sector and propose innovative strategies to target structural determinants, are needed to address asthma morbidities, and more importantly, close the asthma disparity gap.
Immunohistochemical characterization of the anti-Müllerian hormone receptor type 2 (AMHR-2) in human testes
Authors: Sansone A. , Isidori A. M. , Kliesch S. , Schlatt S.
Published: February 2020

Purpose

In males, AMH is secreted by immature Sertoli cells; following exposure to endogenous androgens, Sertoli cells undergo a process of maturation which ultimately inhibits AMH expression to undetectable levels in the serum. However, expression of AMH receptor (AMHR-2) has never been studied in human testes, and high intratubular concentrations of AMH have been reported in recent literature. We therefore assessed expression of AMHR-2 in several testicular tissue samples by immunohistochemistry (IHC).

Methods

The IHC method was first validated on tissue samples from healthy human testis (n = 2) and from marmoset ovary (n = 1). The same method was then used for assessment on testicular histopathology specimens from patients with mixed atrophy (MA,n = 2), spermatogenetic arrest (SA,n = 2), Sertoli cell-only syndrome (SCO,n = 1), Klinefelter syndrome (KS,n = 1), and nonseminomatous germ cell tumors (NSGCT,n = 1). Tissue samples from two subjects at different pubertal stages (AndroProtect (AP), aged 5 and 14 years) with hematological malignancies were also retrieved.

Results

In adult men, AMHR-2 was expressed on peritubular mesenchymal cells, with patterns closely mirroring α-smooth muscle actin expression. Similar patterns were preserved in almost all conditions; however, in nonseminomatous germ cell tumors the tissue architecture was lost, including AMHR-2 expression. More positive and diffuse staining was observed in tissue samples from prepubertal testes.

Conclusions

In specimens from both healthy and affected testes, AMHR-2 expression appears weaker in adult than in prepubertal tissue sections. The persistence of AMHR-2 expression seemingly hints at a possible effect of intratesticular AMH on the tubular walls.
Could the kinetin riboside be used to inhibit human prostate cell epithelial–mesenchymal transition?
Authors: Dulińska-Litewka Joanna , Gąsiorkiewicz Bartosz , Litewka Aleksandra , Gil Dorota , Gołąbek Tomasz , Okoń Krzysztof
Published: February 2020

The epithelial–mesenchymal transition (EMT) is a molecular process connected to higher expression of vimentin and increased activity of transcription factors (Snail, Twist) which restrains E-cadherin. EMT has been linked to prostate cancer metastatic potential, therapy resistance, and poor outcomes. Kinetin riboside (9-(b-dribofuranosyl)-6-furfurylaminopurine, KR) is a naturally occurring cytokinin, which induces apoptosis and shows strong antiproliferative activity against various human cancer cell lines. To establish the effect of KR on human prostate cell lines, expression of, e.g. AR, E-, N-cadherins, Vimentin, Snail, Twist, and MMPs, was analysed at mRNA and protein levels using Western Blot and RT-PCR and/or RQ-PCR techniques. KR inhibited the growth of human prostate cancer cells, but also, to a small extent, of normal cells. This effect depended on the type of the cells and their androgen sensitivity. KR also decreased the level of p-Akt, which takes part in androgen signalling modulation. The antiapoptotic Bcl-2 protein was down-regulated in cancer cell lines, while that of Bax is up-regulated upon KR exposure. KR contributed to re-expression of the E-cadherin as well as to significant changes in cell migration. Taken together, our results indicate for the first time that KR can be proposed as a factor for signalling pathways regulation that participates in the inhibition of development of aggressive forms of prostate cancer, and may alter the approach to therapeutic interventions. We propose KR as a potent inhibitor of EMT in human prostate cells.
Correction to: Liquid biopsy in oncology: a consensus statement of the Spanish Society of Pathology and the Spanish Society of Medical Oncology
Authors: Remon J. , García-Campelo R. , de Álava E. , Vera R. , Rodríguez-Peralto J. L. , Rodríguez-Lescure Á. , Bellosillo B. , Garrido P. , Rojo F. , Álvarez-Alegret R.
Published: February 2020

The article Liquid biopsy in oncology.
Molecular profiling in breast cancer—ready for clinical routine?
Authors: Tendl Kristina A. , Bago-Horvath Zsuzsanna
Published: February 2020

The herald of genomic testing opened novel diagnostic and therapeutic possibilities for many tumor entities. For breast cancer, molecular profiling has become an integral part of disease management on multiple levels. Genetic testing allows for the identification of hereditary cancer syndromes in patients with a family history of malignancies and contributes to the successful prevention of breast cancer. In early breast cancer, several prospective randomized trials demonstrated the prognostic significance of commercially available mRNA-based gene expression analyses, which now have become part of standard of care in the adjuvant setting. In advanced breast cancer, testing for targetable mutations ensures personalized cancer treatment. Poly-ADP-ribose polymerase (PARP) inhibitors provide the first targeted alternative for patients with BRCA 1/2-associated breast cancer. In advanced breast cancer of luminal type, the detection of Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) mutations provides a novel treatment option with alpelisib, a PIK3CA inhibitor. Further targetable mutations include NTRK3 in rare cases of secretory breast carcinoma and human epidermal growth factor receptor 2 (HER2). Recent data support the importance of the analysis of circulating tumor cells and cell-free DNA. These “liquid biopsies” open novel possibilities of molecular profiling. However, clinical benefit of such analyses remains to be confirmed.
The Eocene flora of Tatabánya “marl-mine” (N Hungary)
Authors: Erdei Boglárka , Wilde Volker
Published: February 2020

The middle Eocene (Lutetian) fossil plant assemblage from Tatabánya (N Hungary) comprises plant remains preserved mostly as impressions. Remains of angiosperms are represented by Lauraceae (Laurophyllumdiv. sp.,DaphnogeneUnger), Rhamnaceae (ZiziphusMiller), Malvaceae s.l. (ByttneriopsisZ.Kvaček et Wilde), Leguminosae, and Palmae, and the occurrence of other families, i.e., Dioscoreaceae, Myrtaceae, Fagaceae, Anacardiaceae, Berberidaceae, Juglandaceae, and Theaceae, is uncertain. The scarcity of gymnosperms is a character similar to the coeval floras of Csordakút (N Hungary) and Girbou in Romania. The presence ofZiziphus ziziphoides(Unger) Weyland, high number of linear shaped leaves with entire margin and coriaceous texture (Lauraceae vel Fagaceae), and small-leaved Leguminosae suggests a “subhumid” character of the vegetation, which is recognisable also in early Palaeogene floras of eastern Central and Southeastern Europe, e.g., the Tard Clay floras in Hungary and floras of Serbia/Macedonia. In contrast, the Eocene floras from Central/Western Europe are indicative of a generally non-xerophytic character, e.g., Staré Sedlo in Bohemia, Messel, Geiseltal, and the Weisselster Basin floras in Germany. A frost-free climate with high mean annual temperatures similar to that estimated for coeval European floras may also be inferred for the Tatabánya flora.
Sources of Particulate Organic Matter across Mangrove Forests and Adjacent Ecosystems in Different Geomorphic Settings
Authors: Saavedra-Hortua Daniel A. , Friess Daniel A. , Zimmer Martin , Gillis Lucy Gwen
Published: February 2020

Mangrove forests are among the world’s most productive ecosystems and provide essential ecosystem services such as global climate regulation through the sequestration of carbon. A detailed understanding of the influence of drivers of ecosystem connectivity (in terms of exchange of suspended particulate organic matter), such as geomorphic setting and carbon stocks, among coastal ecosystems is important for being able to depict carbon dynamics. Here, we compared carbon stocks, CO2fluxes at the sediment-air interface, concentrations of dissolved organic carbon and suspended particulate organic carbon across a mangrove-seagrass-tidal flat seascape. Using stable isotope signatures of carbon and nitrogen in combination with MixSIAR models, we evaluated the contribution of organic matter from different sources among the different seascape components. Generally, carbon concentration was higher as dissolved organic carbon than as suspended particulate matter. Geomorphic settings of the different locations reflected the contributions to particulate organic matter of the primary producers. For example, the biggest contributors in the riverine location were mangrove trees and terrestrial plants, while in fringing locations oceanic and macroalgal sources dominated. Anthropogenic induced changes at the coastal level (i.e. reduction of mangrove forests area) may affect carbon accumulation dynamics in adjacent coastal ecosystems.
The Social Impact of Accounting Processes on Benefit Claimants in the UK
Authors: Smith Julia A. , Doolan Elena
Published: February 2020

The accounting processes of categorisation and classification are inherent in modern-day welfare systems, though little has been done to investigate the link these have to the social consequences for benefit claimants within these systems. This paper uses research from both primary and secondary sources to show how UK welfare reform has affected claimants and their inalienable human rights since its introduction in 2012. The data gathered for this work combine face-to-face interview data with press releases, and data and reports compiled and published both by the government and independent bodies. Face-to-face interviews were conducted with two illustrative participants, who were identified as being excellent examples of individuals with a close working knowledge of the welfare system. In addition to the primary data gathered, several sources of secondary data are used within the analysis to identify facts, figures and quotations from reliable government sources. Our analysis uncovers that the accounting processes inherent in the system have helped foster a culture of stigmatisation, food bank dependency and financial and emotional hardship for vulnerable welfare claimants in today’s society.
The Endplate and Trabecular Bone in Lumbar Degenerative Disc Disease: A Narrative Review
Authors: Marjoram Tom
Published: February 2020

To review the current knowledge surrounding degenerative disc disease focusing on the changes taking place in the end plate and trabecular bone. A narrative review of the current literature. An age-related reduction in blood supply to the disc contributes to tissue degradation. Degeneration, separate from this process, represents a disruption of the normal homeostasis. A process of vascular and sensory nerve in-growth in the annulus and localised areas of the end plate is associated with markers of inflammation and may represent a pain source. Treatment with local anti-inflammatories has, at best, mixed results. Bone mechanical indentation testing has been used to classify changes in ageing and degeneration demonstrating a location-dependant reduction in strength specific to each process. Modic changes include a process of inflammation, alteration of the mechanical and chemical environment and changes in bone turnover. The underlying cause for their development has multiple explanations including mechanical overload and microfracture, infection and inflammation in response to herniation of disc material through the end plate. We do know, however, that they seem to be at least partially reversible and not all are symptomatic. This reversibility potentially indicates an avenue of exploration for therapy. Restoring the complex balance of disc homeostasis may hold some promise and will rely on greater understanding of the pathological and material changes occurring at the disc-bone interface and their correlation with clinical imaging. Current treatment may be optimised with an understanding of the mechanical environment of the disc in patient subgroups.
A Postdigital Exploration of Online Postgraduate Learning in Healthcare Professionals: A Horizontal Conception
Authors: Aitken Gillian
Published: February 2020

Holistic evaluation of educational quality necessitates considering novel and theorized measures of quality as well as more instrumental metrics. Online learning is increasingly valued by working professionals as a means of gaining a postgraduate qualification while employed, but this area of education is undertheorized and investigated. Online learning is often discussed in instrumental terms, as if abstracted from the social and material settings in which learning and work take place, but my own conversations with student and graduates about the impact of their studies contrast strongly with such views and motivated this work. Adopting a postdigital perspective, I present an activity theory analysis of interviews with students and staff about the value and perceived impact of online postgraduate programmes in healthcare professions. Four themes are identified that describe how students learning moves horizontally within and across academic and clinical settings: crossing boundaries, ripple effect, eroding structures and hierarchies and expansion. Teaching is delivered online, but learning occurs as the students move through the various contexts they inhabit. The pedagogical approaches required to realize the potential value of these programmes should not be based on the online delivery or the technologies used, but the particular needs of the student group.
Trauma and identity: A reciprocal relationship?
Authors: Berman Steven L. , Montgomery Marilyn J. , Ratner Kaylin
Published: February 2020

Trauma can alter the course of identity development and destabilize existing identity commitments. Trauma, whether past or current, can also impact the resources a person brings to identity work. However, identity can also be a lens through which trauma is perceived and interpreted, helping to determine whether a traumatic experience results in posttraumatic stress disorder or posttraumatic growth. Despite the apparent implications each construct has for the other, the scholarship at the intersection of trauma and identity remains sparse. This Special Issue explores how and when trauma and identity influence one another by considering their association across various adolescent populations, methodologies, traumatic event types, and facets of identity. In doing so, this Special Issue lays the groundwork necessary for exploring, proposing, and testing more complex and nuanced reciprocal relations models between identity and trauma.
Latin American Society Today
Authors: Benza Gabriela , Kessler Gabriel
Published: February 2020

This Element presents the main characteristics of the current social structure in Latin America. We focus on demographic trends, migration, families, incomes, education, health and housing, and examine the general policy trends for all of these issues. Our main questions are: What is the social structure in Latin America like today? What changes have taken place in recent decades, particularly since the turn of the millennium? We argue that although in some dimensions there are continuities, including the persistence of problems from the past, we believe that the Latin American social structure, viewed as a whole, experienced significant transformations.
Environmental worldviews of Serbian and Macedonian school students
Authors: Srbinovski Mile , Stanišić Jelena
Published: February 2020

The objectives of this study were to assess the dimensionality of the revised New Environmental Paradigm (NEP) Scale in Serbian and Macedonian culture, and to use it to explore the environmental worldviews of young people in Serbia and the Republic of North Macedonia. A total of 850 pupils aged between 13 and 15 from 11 schools (5 elementary schools and 6 secondary schools) took part in this research. The dataset obtained from the scale was analysed via the principal component analysis factor extraction method, and a varimax rotation was applied. This study found all items load on four dimensions: Balance of Nature, Humans over Nature, Limits to Growth and Environmental Philosophy. Differences between subgroups occur in three out of four dimensions. The students’ environmental worldviews were determined by providing the frequency distribution of their responses. Both subgroups in the Republic of North Macedonia and Serbia are (slightly) environmentally conscious, with an ecological view of the environment. Macedonian school students have a slightly higher NEP score than their peers in Serbia, indicating more environmentally protective attitudes among them. The participants did not see the two paradigms as mutually exclusive, as do members of some industrialised societies. The rejection of the Dominant Social Paradigm (DSP) by the NEP is a phenomenon that could well only be present in Western societies, whereas in less industrialised societies, the NEP and DSP could coexist in a comprehensive environmental view. With minor alterations such as word substitutions to facilitate easy comprehension of items by the respondents, the revised NEP scale will show more universal applicability outside developed communities.
The impact of capitalist-led neoliberal agenda’s on parents and their children
Authors: Sanders Rachael
Published: February 2020

One of the most important social relationships in any community is that of parent and child. Parents and primary caregivers are typically tasked with raising their children; however, they are but one of many social agents and structures that contribute to childrens’ overall socialisation. Children’s beliefs, values and behaviours are influenced by the broader social systems in which they are raised, including social and economic ideologies. This commentary aims to build an argument based on a broad collection of literature and research, that Australia’s current variegated form of neoliberalism has the potential to create friction within the parent–child relationship, and questions about the social morality of this position are raised.
Collaboration and Cooperation of Public Health Service Management in China
Authors: Qiu Wuqi , Chu Cordia , Wang Kun , Meng Yueli , Yang Yujie , Mao Ayan
Published: February 2020

Objectives:

Collaboration and cooperation are critical for public health management. Nevertheless, collaboration and cooperation between government departments, as well as other entities, are still in a weak condition in China. This article analyzes the status of collaboration and cooperation in the management of public health services in China and explores the problems and gives strategic suggestions for strengthening collaboration and cooperation in the development of public health service systems in China, in order to provide a reference for improvement of public health management in the future.

Methods:

This study uses a qualitative case study approach, including documents review, in-depth interview, and focus group.

Results:

The main problems of collaboration and cooperation in public health service management in China include problems of effective collaboration and cooperation between institutions and relevant departments, public information platform, and implementation of public health and health promotion. On this basis, several relevant policy recommendations are put forward.

Conclusions:

Collaboration and cooperation are critical for the overall coordination and sustainable development of public health in China, and there is still work to be done in order to achieve appropriate cooperation and collaboration between different entities in the provision of public health services.
The Dead and their Possessions: The Declining Agency of the Cadaver in Early Medieval Europe
Authors: Brownlee Emma Claire
Published: February 2020

Between the sixth and eighth centuriesad, the practice of furnished burial was widely abandoned in favour of a much more standardized, unfurnished rite. This article examines that transition by considering the personhood and agency of the corpse, the different ways bonds of possession can form between people and objects, and what happens to those bonds at death. By analysing changing grave good use across western Europe, combined with an in-depth analysis of the Alamannic cemetery of Pleidelsheim, and historical evidence for perceptions of the corpse, the author argues that the change in grave good use marks a fundamental change in the perception of corpses.
Refinement of the Chronology of La Quemada, Zacatecas, Mexico, Using Ceramic Seriation
Authors: Torvinen Andrea , Nelson Ben A.
Published: February 2020

During the Epiclassic period (AD 600–900), the northern frontier of Mesoamerica consisted of a regional network of polities focused on large, hilltop centers, including the site of La Quemada in the Malpaso Valley of Zacatecas, Mexico. Although extensive archaeological research has been conducted at the site, the refinement of its chronology is essential for two reasons: (1) to establish the chronological control necessary to characterize social processes diachronically and (2) to ensure that the occupational history of La Quemada is accurately integrated into the regional chronology of the northern frontier. A combination of frequency seriation, correspondence analysis, and discriminant function analysis results in the recognition of three occupational phases across the areas excavated by the La Quemada-Malpaso Valley Archaeological Project (LQ-MVAP). Our three-phase chronology independently confirms both the intra-context ordering of analytic units and the previously proposed growth trajectory of the site: beginning in the monumental core, expanding into the western flank, and later retracting back into the core. The separation of the LQ-MVAP material record into chronological phases means it is now possible to track changes in the social processes that may have contributed to the formation, maintenance, and decline of La Quemada and other northern frontier polities.
Impact of industrial cream heat treatments on the protein composition of the milk fat globule membrane
Authors: Hansen Steffen F. , Petrat-Melin Bjørn , Rasmusen Jan T. , Larsen Lotte B. , Wiking Lars
Published: February 2020

The impact of cream processing on milk fat globule membrane (MFGM) was assessed in an industrial setting for the first time. Three creams and their derived MFGM fractions from different stages of the pasteurization procedure at a butter dairy were investigated and compared to a native control as well as a commercial MFGM fraction. The extent of cross-linking of serum proteins to MFGM proteins increased progressively with each consecutive pasteurization step. Unresolved high molecular weight aggregates were found to consist of both indigenous MFGM proteins and β-lactoglobulin as well as αs1- and β-casein. With regards to fat globule stability and in terms of resistance towards coalescence and flocculation after cream washing, single-pasteurized cream exhibited reduced sensitivity to cream washing compared to non- and double-pasteurized creams. Inactivation of the agglutination mechanism and the increased presence of non-MFGM proteins may determine this balance between stable and non-stable fat globules.
Nucleation and growth of Si nanoparticles under different pulse repetition rates without the baffle for nanosecond pulsed laser-ablated deposition
Authors: Deng Z. C. , Pang X. X. , Ding X. C. , Chu L. Z. , Meng X. D. , Wang Y. L.
Published: February 2020

In this article, Si nanoparticle (NP) films were prepared by pulsed laser ablation (PLA) in the argon atmosphere of 10 Pa at room temperature under different pulse repetition rates from 1 to 40 Hz without the baffle. Different from the conventional PLA method, the substrates were placed below and parallel to the ablated plume axis. The obtained films containing NPs were characterized by scanning electron microscopy and Raman spectrometer. The experimental results under constant laser fluence demonstrate the strong dependence of the mean size and the area number density of NPs on the repetition rate. Specifically, with the increase of pulse repetition rate, the mean size of the NPs in the film first decreases and reaches its minimum at 20 Hz, and then increases after 20 Hz, and decreases again till 40 Hz. The area number density shows the contrary trend versus mean size. The in situ diagnostic results of Langmuir probe denote the ablated Si ion density increases monotonously with the increase of repetition rate, while the temperature is almost constant. Combining with the nucleation probability, the growth/aggregation duration of NPs in the “nucleation region” and the effect of the baffle, the influence of pulse repetition rate on the formation of NPs is addressed. It is found that the repetition rate impacts the growth modes of NPs (i.e., growth and aggregation). 1–20, 20–30, and 30–40 Hz, respectively, correspond to growth-, aggregation-, and growth-controlled rate ranges without the baffle; however, 1–10, 10–20, and 20–40 Hz, respectively, correspond to growth-controlled, aggregation/growth-coexisted, and aggregation-controlled rate ranges with the baffle.
An analysis of the European Union’s conservation funding allocation by habitat and country
Authors: Mammides Christos , Kirkos George
Published: February 2020

Many of Europe’s unique habitats are highly threatened. In order to tackle these threats, the European Union (EU) is annually financing, mainly through its LIFE programme, conservation actions aimed at improving the conservation status of its habitats. We analysed the allocation of the programme’s budget since its inception in 1992 and we found that the number of projects implemented within the EU member states is only weakly related to the number of habitats within them (R2= 0.39). In some states, fewer than 25% of the habitats have been funded, while in others, more than 75% of the habitats have been funded. There are also disparities in terms of which habitats are being funded; a quarter of them have never received any funding, while others have been targeted by multiple projects. Transnational cooperation between the states is low, further perpetuating the aforementioned disparities. Projects are implemented almost exclusively within the recipient state, often irrespectively of the conservation status of the targeted habitats in other states. We recommend that the EU addresses these disparities by encouraging projects in underfunded states, especially in habitats with unfavourable conservation statuses. Moreover, the EU should encourage transnational cooperation in order to promote effective conservation across the EU and to help underfunded states build their capacity.
Which types of reason-giving and storytelling are good for deliberation? Assessing the discussion dynamics in legislative and citizen forums
Authors: Maia Rousiley C. M. , Cal Danila , Bargas Janine , Crepalde Neylson J. B.
Published: February 2020

Real-world political discussions usually mix reason-giving and storytelling in complex ways, but the interplay between these practices remains essentially unexamined. This article builds a theoretical argument based on a systemic approach for investigating such forms of communication in institutionally organized forums and informal settings alike. It contends that generalizations should not be made about the role of giving reasons and telling stories for good deliberation. A distinctive analytical framework is developed for examining these practices when deliberation is high quality, low quality, or changing (high to low or low to high). Drawing on data about discussions on reducing the criminal responsibility age in Brazil in legislative public hearings and face-to-face groups, the analysis uncovers variations in the structure of reasons and stories and shifts in their functions in optimal and suboptimal moments of deliberation. By incorporating the pragmatic dimension of interactions into the analysis, this paper contributes to advancing comparative analyses in different contexts.
Pattern of Latitudinal Distribution of Ionospheric Irregularities in the African Region and the Effect of March 2015 St. Patrick's Day Storm
Authors: Bolaji O. S. , Adebiyi S. J. , Fashae J. B. , Ikubanni S. O. , Adenle H. A. , Owolabi C.
Published: February 2020

This paper investigates the latitudinal distribution of quiet and storm time irregularities over the African ionosphere in the month of March 2015. The average rate of change in total electron content (TEC) index (ROTIave) calculated from Global Positioning System data is used as a proxy for the irregularities. The result during the quiet condition shows that irregularities are mostly observed between 19:00 and 00:00 LT regardless of the hemisphere. Its appearance in the Southern Hemisphere is earlier, though with less severity mainly around the equatorward edge of the equatorial anomaly peak. The peak of its development occurred at 21:00 LT, as it is observed in all the latitudes except those outside the equatorial region. The strength is found to be most severe at ∼12° magnetic latitude (up to 1.10 TECU/min.) in the south. Beyond ∼18° magnetic latitude, it is rarely noticed in the south. However, it is not observed around this latitude in the north, indicating a major hemispheric asymmetry in terms of the latitudinal boundary between the Northern and Southern Hemispheres. Furthermore, its disappearance is found to be most rapid around the poleward verge of the equatorial anomaly region particularly in the Southern Hemisphere. In contrast to quiet time observations, irregularities were absent in all latitudes during the storm days considered. This can be attributed to the local time of the storm's onset and the possible imposition of westward electric fields in the dusk period.
Temporomandibular joint damage in K/BxN arthritic mice
Authors: Kuchler-Bopp Sabine , Mariotte Alexandre , Strub Marion , Po Chrystelle , De Cauwer Aurore , Schulz Georg , Van Bellinghen Xavier , Fioretti Florence , Clauss François , Georgel Philippe , Benkirane-Jessel Nadia , Bornert Fabien
Published: February 2020

Rheumatoid arthritis (RA) is an autoimmune disease affecting 1% of the world population and is characterized by chronic inflammation of the joints sometimes accompanied by extra-articular manifestations. K/BxN mice, originally described in 1996 as a model of polyarthritis, exhibit knee joint alterations. The aim of this study was to describe temporomandibular joint (TMJ) inflammation and damage in these mice. We used relevant imaging modalities, such as micro-magnetic resonance imaging (μMRI) and micro-computed tomography (μCT), as well as histology and immunofluorescence techniques to detect TMJ alterations in this mouse model. Histology and immunofluorescence for Col-I, Col-II, and aggrecan showed cartilage damage in the TMJ of K/BxN animals, which was also evidenced by μCT but was less pronounced than that seen in the knee joints. μMRI observations suggested an increased volume of the upper articular cavity, an indicator of an inflammatory process. Fibroblast-like synoviocytes (FLSs) isolated from the TMJ of K/BxN mice secreted inflammatory cytokines (IL-6 and IL-1β) and expressed degradative mediators such as matrix metalloproteinases (MMPs). K/BxN mice represent an attractive model for describing and investigating spontaneous damage to the TMJ, a painful disorder in humans with an etiology that is still poorly understood.
Broadband 200-nm second-harmonic generation in silicon in the telecom band
Authors: Singh Neetesh , Raval Manan , Ruocco Alfonso , Watts Michael R.
Published: February 2020

Silicon is well known for its strong third-order optical nonlinearity, exhibiting efficient supercontinuum and four-wave mixing processes. A strong second-order effect that is naturally inhibited in silicon can also be observed, for example, by electrically breaking the inversion symmetry and quasi-phase matching the pump and the signal. To generate an efficient broadband second-harmonic signal, however, the most promising technique requires matching the group velocities of the pump and the signal. In this work, we utilize dispersion engineering of a silicon waveguide to achieve group velocity matching between the pump and the signal, along with an additional degree of freedom to broaden the second harmonic through the strong third-order nonlinearity. We demonstrate that the strong self-phase modulation and cross-phase modulation in silicon help broaden the second harmonic by 200 nm in the O-band. Furthermore, we show a waveguide design that can be used to generate a second-harmonic signal in the entire near-infrared region. Our work paves the way for various applications, such as efficient and broadband complementary-metal oxide semiconductor based on—chip frequency synthesizers, entangled photon pair generators, and optical parametric oscillators.
The RUNX1-ETO target gene RASSF2 suppresses t(8;21) AML development and regulates Rac GTPase signaling
Authors: Stoner Samuel A. , Liu Katherine Tin Heng , Andrews Elizabeth T. , Liu Mengdan , Arimoto Kei-Ichiro , Yan Ming , Davis Amanda G. , Weng Stephanie , Dow Michelle , Xian Su , DeKelver Russell C. , Carter Hannah , Zhang Dong-Er
Published: February 2020

Large-scale chromosomal translocations are frequent oncogenic drivers in acute myeloid leukemia (AML). These translocations often occur in critical transcriptional/epigenetic regulators and contribute to malignant cell growth through alteration of normal gene expression. Despite this knowledge, the specific gene expression alterations that contribute to the development of leukemia remain incompletely understood. Here, through characterization of transcriptional regulation by the RUNX1-ETO fusion protein, we have identified Ras-association domain family member 2 (RASSF2) as a critical gene that is aberrantly transcriptionally repressed in t(8;21)-associated AML. Re-expression of RASSF2 specifically inhibits t(8;21) AML development in multiple models. Through biochemical and functional studies, we demonstrate RASSF2-mediated functions to be dependent on interaction with Hippo kinases, MST1 and MST2, but independent of canonical Hippo pathway signaling. Using proximity-based biotin labeling we define the RASSF2-proximal proteome in leukemia cells and reveal association with Rac GTPase-related proteins, including an interaction with the guanine nucleotide exchange factor, DOCK2. Importantly, RASSF2 knockdown impairs Rac GTPase activation, and RASSF2 expression is broadly correlated with Rac-mediated signal transduction in AML patients. Together, these data reveal a previously unappreciated mechanistic link between RASSF2, Hippo kinases, and Rac activity with potentially broad functional consequences in leukemia.
Ibrutinib treatment inhibits breast cancer progression and metastasis by inducing conversion of myeloid-derived suppressor cells to dendritic cells
Authors: Varikuti Sanjay , Singh Bhawana , Volpedo Greta , Ahirwar Dinesh K. , Jha Bijay K. , Saljoughian Noushin , Viana Agostinho G. , Verma Chaitenya , Hamza Omar , Halsey Gregory , Holcomb Erin A. , Maryala Ritvik J. , Oghumu Steve , Ganju Ramesh K. , Satoskar Abhay R.
Published: February 2020

Background

Ibrutinib is a Bruton’s tyrosine kinase (BTK) and interleukin-2-inducible kinase (ITK) inhibitor used for treating chronic lymphocytic leukaemia (CLL) and other cancers. Although ibrutinib is known to inhibit the growth of breast cancer cell growth in vitro, its impact on the treatment and metastasis of breast cancer is unclear.

Methods

Using an orthotopic mouse breast cancer model, we show that ibrutinib inhibits the progression and metastasis of breast cancer.

Results

Ibrutinib inhibited proliferation of cancer cells in vitro, and Ibrutinib-treated mice displayed significantly lower tumour burdens and metastasis compared to controls. Furthermore, the spleens and tumours from Ibrutinib-treated mice contained more mature DCs and lower numbers of myeloid-derived suppressor cells (MDSCs), which promote disease progression and are linked to poor prognosis. We also confirmed that ex vivo treatment of MDSCs with ibrutinib switched their phenotype to mature DCs and significantly enhanced MHCII expression. Further, ibrutinib treatment promoted T cell proliferation and effector functions leading to the induction of antitumour TH1 and CTL immune responses.

Conclusions

Ibrutinib inhibits tumour development and metastasis in breast cancer by promoting the development of mature DCs from MDSCs and hence could be a novel therapeutic agent for the treatment of breast cancer.
Bone-derived mesenchymal stem cells alleviate compression-induced apoptosis of nucleus pulposus cells by N6 methyladenosine of autophagy
Authors: Li Gaocai , Song Yu , Liao Zhiwei , Wang Kun , Luo Rongjin , Lu Saideng , Zhao Kangcheng , Feng Xiaobo , Liang Hang , Ma Liang , Wang Bingjin , Ke Wencan , Yin Huipeng , Zhan Shengfeng , Li Shuai , Wu Xinghuo , Zhang Yukun , Yang Cao
Published: February 2020

N6 methyladenosine (m6A) is one of the most prevalent epitranscriptomic modifications of mRNAs, and plays a critical role in various bioprocesses. Bone-derived mesenchymal stem cells (BMSCs) can attenuate apoptosis of nucleus pulposus cells (NPCs) under compression; however, the underlying mechanisms are poorly understood. This study showed that the level of m6A mRNA modifications was decreased, and the autophagic flux was increased in NPCs under compression when they were cocultured with BMSCs. We report that under coculture conditions, RNA demethylase ALKBH5-mediated FIP200 mRNA demethylation enhanced autophagic flux and attenuated the apoptosis of NPCs under compression. Specific silencing of ALKBH5 results in impaired autophagic flux and a higher proportion of apoptotic NPCs under compression, even when cocultured with BMSCs. Mechanistically, we further identify that the m6A “reader” YTHDF2 is likely to be involved in the regulation of autophagy, and lower m6A levels in the coding region of FIP200 lead to a reduction in YTHDF2-mediated mRNA degradation of FIP200, a core molecular component of the ULK1 complex that participates in the initiating process of autophagy. Taken together, our study reveals the roles of ALKBH5-mediated FIP200 mRNA demethylation in enhancing autophagy and reducing apoptosis in NPCs when cocultured with BMSCs.
Deficiency of the ER-stress-regulator MANF triggers progressive outer hair cell death and hearing loss
Authors: Herranen Anni , Ikäheimo Kuu , Lankinen Tuuli , Pakarinen Emmi , Fritzsch Bernd , Saarma Mart , Lindahl Maria , Pirvola Ulla
Published: February 2020

The non-conventional neurotrophic factor mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-resident protein that promotes ER homeostasis. MANF has a cytoprotective function, shown in the central nervous system neurons and pancreatic beta cells. Here, we report that MANF is expressed in the hair cells and neurons and in selected non-sensory cells of the cochlea and that Manf inactivation triggers upregulation of the ER chaperones in these cells. However, Manf inactivation resulted in the death of only outer hair cells (OHCs), the cells responsible for sound amplification in the cochlea. All OHCs were formed in Manf-inactivated mice, but progressive OHC death started soon after the onset of hearing function. The robust OHC loss was accompanied by strongly elevated hearing thresholds. Conditional Manf inactivation demonstrated that MANF has a local function in the cochlea. Immunostainings revealed the upregulation of CHOP, the pro-apoptotic component of the unfolded protein response (UPR), in Manf-inactivated OHCs, linking the UPR to the loss of these cells. The phenotype of Manf-inactivated OHCs was distinctly dependent on the mouse strain, such that the strains characterized by early-onset age-related hearing loss (C57BL/6J and CD-1) were affected. These results suggest that Manf deficiency becomes detrimental when accompanied by gene mutations that predispose to hearing loss, by intensifying ER dyshomeostasis. Together, MANF is the first growth factor shown to antagonize ER stress-mediated OHC death. MANF might serve as a therapeutic candidate for protection against hearing loss induced by the ER-machinery-targeting stressors.
Hepatocyte caveolin-1 modulates metabolic gene profiles and functions in non-alcoholic fatty liver disease
Authors: Han Mei , Piorońska Weronika , Wang Sai , Nwosu Zeribe Chike , Sticht Carsten , Wang Shanshan , Gao Yan , Ebert Matthias Philip , Dooley Steven , Meyer Christoph
Published: February 2020

Caveolin-1 (CAV1) is a crucial regulator of lipid accumulation and metabolism. Previous studies have shown that global Cav1 deficiency affects lipid metabolism and hepatic steatosis. We aimed to analyze the consequences of hepatocyte-specific Cav1 knockout under healthy conditions and upon non-alcoholic fatty liver disease (NAFLD) development. Male and female hepatocyte-specific Cav1 knockout (HepCAV1ko) mice were fed a methionine/choline (MCD) deficient diet for 4 weeks. MCD feeding caused severe hepatic steatosis and slight fibrosis. In addition, liver function parameters, i.e., ALT, AST, and GLDH, were elevated, while cholesterol and glucose level were reduced upon MCD feeding. These differences were not affected by hepatocyte-specific Cav1 knockout. Microarray analysis showed strong differences in gene expression profiles of livers from HepCAV1ko mice compared those of global Cav1 knockout animals. Pathway enrichment analysis identified that metabolic alterations were sex-dimorphically regulated by hepatocyte-specific CAV1. In male HepCAV1ko mice, metabolic pathways were suppressed in NAFLD, whereas in female knockout mice induced. Moreover, gender-specific transcription profiles were modulated in healthy animals. In conclusion, our results demonstrate that hepatocyte-specific Cav1 knockout significantly altered gene profiles, did not affect liver steatosis and fibrosis in NAFLD and that gender had severe impact on gene expression patterns in healthy and diseased hepatocyte-specific Cav1 knockout mice.
Nogo-A-targeting antibody promotes visual recovery and inhibits neuroinflammation after retinal injury
Authors: Baya Mdzomba Julius , Joly Sandrine , Rodriguez Léa , Dirani Ali , Lassiaz Patricia , Behar-Cohen Francine , Pernet Vincent
Published: February 2020

N-Methyl-D-aspartate (NMDA)-induced neuronal cell death is involved in a large spectrum of diseases affecting the brain and the retina such as Alzheimer’s disease and diabetic retinopathy. Associated neurological impairments may result from the inhibition of neuronal plasticity by Nogo-A. The objective of the current study was to determine the contribution of Nogo-A to NMDA excitotoxicity in the mouse retina. We observed that Nogo-A is upregulated in the mouse vitreous during NMDA-induced inflammation. Intraocular injection of a function-blocking antibody specific to Nogo-A (11C7) was carried out 2 days after NMDA-induced injury. This treatment significantly enhanced visual function recovery in injured animals. Strikingly, the expression of potent pro-inflammatory molecules was downregulated by 11C7, among which TNFα was the most durably decreased cytokine in microglia/macrophages. Additional analyses suggest that TNFα downregulation may stem from cofilin inactivation in microglia/macrophages. 11C7 also limited gliosis presumably via P.Stat3 downregulation. Diabetic retinopathy was associated with increased levels of Nogo-A in the eyes of donors. In summary, our results reveal that Nogo-A-targeting antibody can stimulate visual recovery after retinal injury and that Nogo-A is a potent modulator of excitotoxicity-induced neuroinflammation. These data may be used to design treatments against inflammatory eye diseases.
Acetate supplementation restores chromatin accessibility and promotes tumor cell differentiation under hypoxia
Authors: Li Yang , Gruber Joshua J. , Litzenburger Ulrike M. , Zhou Yiren , Miao Yu Rebecca , LaGory Edward L. , Li Albert M. , Hu Zhen , Yip Michaela , Hart Lori S. , Maris John M. , Chang Howard Y. , Giaccia Amato J. , Ye Jiangbin
Published: February 2020

Despite the fact that Otto H. Warburg discovered the Warburg effect almost one hundred years ago, why cancer cells waste most of the glucose carbon as lactate remains an enigma. Warburg proposed a connection between the Warburg effect and cell dedifferentiation. Hypoxia is a common tumor microenvironmental stress that induces the Warburg effect and blocks tumor cell differentiation. The underlying mechanism by which this occurs is poorly understood, and no effective therapeutic strategy has been developed to overcome this resistance to differentiation. Using a neuroblastoma differentiation model, we discovered that hypoxia repressed cell differentiation through reducing cellular acetyl-CoA levels, leading to reduction of global histone acetylation and chromatin accessibility. The metabolic switch triggering this global histone hypoacetylation was the induction of pyruvate dehydrogenase kinases (PDK1 and PDK3). Inhibition of PDKs using dichloroacetate (DCA) restored acetyl-CoA generation and histone acetylation under hypoxia. Knocking down PDK1 induced neuroblastoma cell differentiation, highlighting the critical role of PDK1 in cell fate control. Importantly, acetate or glycerol triacetate (GTA) supplementation restored differentiation markers expression and neuron differentiation under hypoxia. Moreover, ATAC-Seq analysis demonstrated that hypoxia treatment significantly reduced chromatin accessibility at RAR/RXR binding sites, which can be restored by acetate supplementation. In addition, hypoxia-induced histone hypermethylation by increasing 2-hydroxyglutarate (2HG) and reducing α-ketoglutarate (αKG). αKG supplementation reduced histone hypermethylation upon hypoxia, but did not restore histone acetylation or differentiation markers expression. Together, these findings suggest that diverting pyruvate flux away from acetyl-CoA generation to lactate production is the key mechanism that Warburg effect drives dedifferentiation and tumorigenesis. We propose that combining differentiation therapy with acetate/GTA supplementation might represent an effective therapy against neuroblastoma.