bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of significant association between selected STAT3 polymorphisms and rheumatoid arthritis in the Polish population
Authors: Stypińska Barbara , Olesińska Marzena , Pawlik Andrzej , Paradowska-Gorycka Agnieszka
Published: May 2018

Objectives

Rheumatoid arthritis (RA) is the most common systemic inflammatory disease and is of unknown etiology. The altered balance between immunosuppressive and inflammatory T cell subpopulations exerts a huge impact on RA pathogenesis. The STAT3 protein regulates genes involved in the immune responses. It regulates maturation of T and B cells. Its abnormal activity is significantly associated with autoimmune diseases and cancer development. We aimed to evaluate the contribution of three potentially functional single nucleotide polymorphisms (SNPs) within the STAT3 gene to susceptibility and severity of RA in the Polish population.

Material and methods

A total of 595 patients with RA and 330 healthy individuals were included in the study. DNA from patients and healthy subjects was obtained from peripheral blood using standard DNA isolating methods. The STAT3 rs1053005, rs1026916 and rs2293152 polymorphisms were genotyped using the TaqMan SNP genotyping assay. The accuracy of SNP genotyping was confirmed using direct DNA sequence analysis.

Results

The distribution of STAT3 polymorphisms did not differ significantly between cases and controls. Our results revealed a tendency only, where rs1026916 AA genotype occurred more frequently in RA patients compared to healthy controls, in codominant (p = 0.09), dominant (p = 0.06) and recessive (p = 0.09) models. STAT3 rs2293152 polymorphism was associated with higher DAS28 (p = 0.014 codominant model; p = 0.003 dominant model), increased number of swollen joints (p = 0.02), higher VAS (p = 0.01) and higher HAQ score (p = 0.05).

Conclusions

We did not observe a significant association between the three studied STAT3 genetic variants and increased susceptibility to or severity of RA. Only the STAT3 rs2293152 polymorphism was associated with parameters that indicate a more severe course of the disease. However, its distribution did not differ between RA and control groups. According to our observations these 3 studied STAT3 SNPs may not be used as risk factors for developing RA.
Vertebral fracture assessment, trabecular bone score and handgrip in a group of postmenopausal women with vertebral fractures – preliminary study
Authors: Amarowicz Jarosław , Czerwiński Edward , Kumorek Anna , Warzecha Maja , Berwecka Małgorzata , Hans Didier
Published: May 2018

Objectives

The aim of our study was to determine a possible correlation between vertebral fractures (indicated by VFA – vertebral fracture assessment), TBS (trabecular bone score) and muscle strength (measured by means of handgrip strength test results) in a group of postmenopausal women.

Material and methods

The study was conducted between 2014 and 2015 in a group of patients of Krakow Medical Centre (KMC). Women who participated in the study were referred to KMC by an attending physician for suspected vertebral fracture. Apart from VFA, patients were additionally tested for bone density (including TBS), muscle strength (by means of a handgrip strength test) and height loss. Altogether 35 patients with an average age of 69.7 years (49–95, SD = 10.49) were included in the study.

Results

In the group of 35 women, VFA analysis demonstrated vertebral fractures in 17 patients (40%). Vertebral height loss suggesting a fracture was revealed in 77 vertebrae. The mean result of the TBS was 1.195 (0.982–1.409, SD = 0.09), which suggests high risk of fracture. The majority of the subjects (65.7%) displayed major bone microarchitecture degradation (TBS < 1.23) and also the highest number of fractures (n = 62, 80.5% of all). There was no correlation between the spine bone mineral density (BMD) score and the TBS result, which confirms studies showing that subjects with the same bone density may have completely different TBS. Bone density (spine BMD) was similar (osteopenic) in groups with or without vertebral fracture (in VFA). We noted a significant correlation (r = 0.45, p < 0.05) between the number of fractured vertebrae and the handgrip score.

Conclusions

VFA should be a part of a standard diagnostic procedure for patients with osteoporotic fractures. When it comes to identifying patients at risk of fracturing vertebrae, muscle strength (handgrip) may have potential use in clinical practice. The predictive value of the TBS in reference to vertebral fractures should be evaluated in bigger randomized studies.
What is the role of angiotensin receptor blockers in treatment of hyperuricemia coexisting with arterial hypertension?
Authors: Nieradko-Iwanicka Barbara
Published: May 2018

Angiotensin receptor blockers or sartans are used to treat arterial hypertension. Hyperuricemia and arterial hypertension often coexist in patients with metabolic syndrome. Also hyperuricemia is correlated with an increased risk of cardiovascular disease and death. There are data suggesting that lowering serum urate may assist in control of arterial hypertension and use of certain drugs for arterial hypertension may reduce the serum uric acid level. The Polish Society of Arterial Hypertension recommends losartan for treatment of arterial hypertension in patients with coexisting hyperuricemia.

The aim of the present review was to find evidence supporting the concept of use and explain the role of sartans in treatment of hyperuricemia.

Thirty-five original and review articles about hyperuricemia and arterial hypertension focusing on the use of sartans in both these medical conditions were analyzed.

In conclusion, sartans should be recommended for treatment of hyperuricemia coexisting with arterial hypertension in patients without bilateral renal artery stenosis and with exclusion of pregnant women.
The impact of nutrition and generally available products such as nicotine and alcohol on rheumatoid arthritis – review of the literature
Authors: Grygielska Jolanta , Raciborski Filip , Kłak Anna , Owoc Jakub
Published: May 2018

Nutrition habits and diet may influence disease development and course. There are no specific recommendations related to rheumatic diseases for a diet that would facilitate treatment. However, some research results suggest that various nutrients may affect the health of patients, especially in the case of inflammatory rheumatic disease such as rheumatoid arthritis (RA). Scientists have been trying to find a relation between inflammatory rheumatic diseases and diet but have never come up with any firm conclusions that would help in determining the model of a diet for such patients. Nevertheless, there are some consistent results that refer to the influence of nutritional behaviours on symptoms of RA. The article presents a review of the research showing that certain nutrients may be beneficial for the course of disease among some RA patients.
Fuzzy and process modelling of contour ridge water dynamics
Authors: Mhizha Alexander , Ndiritu John
Published: May 2018

Abstract. Contour ridges are an in-situ rainwater harvesting technology developed
initially for soil erosion control but are currently also widely promoted
for rainwater harvesting. The effectiveness of contour ridges depends on
geophysical, hydro-climatic and socio economic factors that are highly
varied in time and space. Furthermore, field-scale data on these factors are
often unavailable. This together with the complexity of hydrological
processes at field scale limits the application of classical distributed
process modelling to highly-instrumented experimental fields. This paper
presents a framework that combines fuzzy logic and process-based approach
for modelling contour ridges for rainwater harvesting where detailed field
data are not available. Water balance for a representative contour-ridged
field incorporating the water flow processes across the boundaries is
integrated with fuzzy logic to incorporate the uncertainties in estimating
runoff. The model is tested using data collected during the 2009/2010 and
2010/2011 rainfall seasons from two contour-ridged fields in Zhulube located
in the semi-arid parts of Zimbabwe. The model is found to replicate soil
moisture in the root zone reasonably well (NSE = 0.55 to 0.66 and
PBIAS = −1.3 to 6.1 %). The results show that combining fuzzy logic
and process based approaches can adequately model soil moisture in a contour
ridged-field and could help to assess the water dynamics in contour ridged
fields.
Isotopic composition and elemental concentrations in groundwater in the Kuiseb Basin and the Cuvelai-Etosha Basin, Namibia
Authors: Kgabi Nnenesi A. , Atekwana Eliot , Ithindi Johanna , Uugwanga Martha , Knoeller Kay , Motsei Lebogang , Mathuthu Manny , Kalumbu Gideon , Amwele Hilma R. , Uusizi Rian
Published: May 2018

Abstract. We assessed environmental tracers in groundwater in two
contrasting basins in Namibia; the Kuiseb Basin, which is a predominantly
dry area and the Cuvelai-Etosha Basin, which is prone to alternating floods
and droughts. We aimed to determine why the quality of groundwater was
different in these two basins which occur in an arid environment. We
analysed groundwater and surface water for the stable isotope ratios of
hydrogen (δ2H) and oxygen (δ18O) by cavity
ring-down spectroscopy and metals by inductively coupled plasma mass
spectrometry. The δ2H and δ18O of surface water in
the Cuvelai-Etosha Basin plot on an evaporation trend below the global
meteoric water line (GMWL) and the local meteoric water line (LMWL). The
δ2H and δ18O of some groundwater samples in the
Cuvelai-Etosha Basin also plot on the evaporation trend, indicating recharge
by evaporated rain or evaporated surface water. In contrast, the δ2H and δ18O of groundwater samples in the Kuiseb Basin
plot mostly along the GMWL and the LMWL, indicating direct recharge from
unevaporated rain or unevaporated surface water. Fifty percent of
groundwater samples in the Cuvelai-Etosha Basin was potable (salinity
< 1 ppt) compared to 79 % in the Kuiseb Basin. The high salinity
in the groundwater of the Cuvelai-Etosha Basin does not appear to be caused
by evaporation of water (evapo-concentration) on surface prior to
groundwater recharge, but rather by the weathering of the Kalahari
sediments. The low salinity in the Kuiseb Basin derives from rapid recharge
of groundwater by unevaporated rain and limited weathering of the
crystalline rocks. The order of abundance of cations in the Kuiseb Basin is
Na > K > Ca > Mg vs. Na > Mg > Ca > K
for the Cuvelai-Etosha Basin. For metals in
the Kuiseb Basin the order of abundance is Fe > Al > V > As > Zn
vs. Al > Fe > V> As > Zn
for the Cuvelai-Etosha Basin. The relative
abundance of cations and metals are attributed to the differences in geology
of the basins and the extent of water-rock interaction. Our results show
that the quality of groundwater in Cuvelai-Etosha Basin and Kuiseb Basin
which vary in the extent of aridity, is controlled by the extent of
water-rock interaction at the surface and in the groundwater aquifer.
The Risk-Adjusted Performance of Alternative Investment Funds and UCITS: A Comparative Analysis
Authors: Camilleri Silvio John , Farrugia Ritienne
Published: May 2018

This study evaluates the performance of a selection of Alternative Investment Funds (AIFs), and Undertakings for Collective Investment in Transferable Securities Funds (UCITS) which followed a global geographic focus strategy during the period 2010-2016. These two fund structures are governed by different regulatory frameworks, which have evolved and re-shaped over the years. Various yardsticks are employed to evaluate the risk-adjusted performance of the sampled funds, and Monte-Carlo simulations are used to gauge the possible out-of-sample returns. Most of the sampled funds underperformed the benchmark index in terms of their Sharpe and Treynor ratios. Whilst UCITS registered a better overall performance, AIFs outperformed UCITS towards the end of the sample period. This suggests that investors should not assume that one fund structure is inherently superior to the other, since the relative performance may vary over time.
Empirical Testing of the Impact of Gender and Marital Status on the Price and Trend of Urban Real Estate – Evidence from Provincial Panel Data of China
Authors: Tan Min , Bai Yajie
Published: May 2018

This paper investigates the impact of demographic structure, especially gender and marital status, on the price of regional real estate. This paper utilizes controlled-heteroskedasticity fixed-effect model for the empirical tests based on a panel data set of 30 Chinese provinces from 2011 to 2015. Empirical results show that the gender ratio in the provincial panel data does have a significant negative impact on the regional real estate prices, which implies that when the number of women in a region increases, the real estate price in this region tends to rise. The impact of marital status on the real estate price is not significant according to empirical results.
The Effect of Strategic Vision for the University Authorities in Administrating the Internal Client: A Case Study at Zarqa University
Authors: Alzeaideen Khaled Abdulwahab , Masadeh Majed Abdel-Mohdi
Published: May 2018

The study aims at identifing the concept of strategic vision of the authorities in Zarqa University, identifing the most important elements, and proposing the appropriate mechanisms to meet the future challenges facing the university leader as a result of competition and how to maintain the teaching and non-teaching staff within the institution to enhance loyalty of the 'internal client ' in the future. Strategic vision variables were used; future status was determined, goals achieved by the vision were achieved, university culture was selected, and the appropriate strategy was chosen as independent variables affecting a dependent variable that is is the internal client relations management. The researchers collected the initial data of the study by means of a special questionnaire. The sample consists of (115) out of 300 faculty members at Zarqa University of various qualifications, ranks and experience.The results of the analysis show that there is a strong and significant effect on all elements of the strategic vision on internal client relationship management, and demographic variables (gender, age group, job title and years of experience) contributed intrinsically to the response of the sample regarding the adoption of the strategic vision factors in managing the internal client relations.Based on the findings of the study, the researchers proposed a number of recommendations to the administration of the university, focusing on spreading and supporting positive culture among faculty members, setting specific and clear objectives for the future to all university employees, along with constructing lucid future strategic directions, and updating the vision and mission of the institution. It is also recommended to comprehensively expand the study of the impact of strategic and other organizational factors; and programs and plans of management development on improving the management of relationships with the internal client of the University.
Inny aktywizm w "Historii i czynie" Tadeusza Gajcego, czyli powrót Norwida na marginesach „Sztuki i Narodu”
Authors: Zehnder Christian
Published: May 2018

This paper focuses on the symbolic role attributed to Cyprian Norwid (1821–1883) in
the young poets’ and critics’ circle gathered around the right-wing conspiracy journal Art
and Nation (1942–1944) in occupied Warsaw. They used a paraphrase of Norwid’s words,
“The artist is the organizer of national imagination”, in order to emphasize their aim of an
autonomous and at the same time nationally committed art. However, in many statements
by Andrzej Trzebiński (1922–1943) and Wacław Bojarski (1921–1943), the term “nation”
appears to be more of a performative gesture than a reference to a consistent, historically
evolving reality, as conceived of by Norwid. It was only in the 1944 essay “History and Deed”, never to be printed in the underground, that the circle’s foremost poet Tadeusz Gajcy (1922–1944) critically revisited anti-traditional activism and championed a genuinely “Norwidian”, contemplation-based understanding of creativity.
Czy Emily Dickinson pisała wiersze?
Authors: Magnone Lena
Published: May 2018

The author proposes a reflection on discovering the poet with regard to his creation or construction. This issue is discussed on the example of Emily Dickinson’s works which were published only after her death and were not prepared for print by the author herself. In the light of the latest research on the material dimension of her legacy (starting from Virginia Jackson’s study Dickinson’s Misery: A Theory of Lyric Reading from 2005 to the recently published collection The Gorgeous Nothings. Emily Dickinson’s Envelope Poems), it appears that many of Dickinson’s works were not written in a form that could be recognized as poetic at first glance. A large part was preserved only in notebooks, loose sheets covered with handwriting written in continuo or at odd angles, in a manner adapted to the format of a given scrap of paper, usually a free fragment of a recycled envelope or a torn-off corner of a piece of paper used previously for a different purpose. These texts had to be recognized then by discoverers as poems, and then copied and edited in a way consistent with what was considered lyric poetry in the era. Some of them were then rejected as not falling into the category of poetry and included in the opus of the American only by later researchers. Others, in the first editions treated as poems with time were excluded by historians of literature from this collection. Contrary to the provocative title, the aim of the article is not to answer the question about the status of the texts left by Dickinson. Instead, the author reflects on the poetic criteria ascribed to her works by the first and subsequent readers.
Foscolo w „Kłosach” w 1872 roku: polski epizod pośmiertnej wędrówki
Authors: Ślarzyńska Małgorzata
Published: May 2018

The aim of the article is to present the issue of reception of Ugo Foscolo’s works in Poland. A particular attention is paid to the multipart article in Kłosy from 1872 (No. 374–386) devoted to the Italian artist in connection with the transfer of the poet’s remains – many years after his death in England in 1827 – to the Basilica of Santa Croce in Florence in 1871. The paper discusses the strategies adopted in the description of elements of the poet’s biography, including a sentimental key related to the figure of Quirina Mocenni Magiotti, an economic key and a moralizing key. Emphasizing the experience of emigration and compulsory uprooting of the Italian poet from the family land places this special periodical return from beyond the grave in a new context determined by the situation in Poland and the resulting condition of artists forced to emigrate. The analysis also involves unique Polish translations of three of the most important Foscol’s sonnets (*** [Solcata ho fronte]; “In morte del fratello Giovanni”; “A Zacinto”) included within the frame of the article in Kłosy.
The Unbearable Lightness of Finger Movements: Commentary to Doliński
Authors: Halvor Teigen Karl
Published: May 2018

In the target article, Doliński (2018, this issue) showed that empirical studies of “real” behaviour are an almost extinct species of research, judged from articles published in the most recent volume of JPSP (Journal of Personality and Social Psychology). This finding continues a trend identified by Baumeister and colleagues ten years ago. The reliance on self-reports and rating scales can hardly be explained as an aftermath of the cognitive revolution in psychology, or a preoccupation with measurements and advanced statistical analyses, as Doliński suggests, but is more compatible with the ease of collecting questionnaire data, combined with the pressure to publish large multi-study papers and to obtain approval from ethical review boards. This development is further strengthened by the accessibility of online participant pools. An informal count showed that students participating for course credit were in 2006 involved more than 90% of empirical JPSP studies, as against 22.5% in 2017. In contrast, Amazon Mechanical Turk workers, non-existent in 2006, participated in 55.3% of the empirical studies published in the most recent volume. Parallel to this development the number of participants per study and the number of studies per article have vastly increased.
Une différence à inventer : l’américanité sauvage de Supervielle
Authors: Bernadet Arnaud
Published: May 2018

L’expression de l’américanité chez Jules Supervielle est l’objet de plusieurs récidives littéraires. À mesure qu’il se dégage de l’influence romantique et parnassienne, encore prégnante dans Brumes du passé et Comme des voiliers, le poète apprend à « plier à son goût » la Muse uruguayenne. De Poèmes à Débarcadères, l’américanité se révèle plus encore inséparable d’une quête de l’identité. Elle traduit l’exigence d’une signature, capable enfin d’assigner à l’oeuvre ce que Supervielle appelle le « ton réel ». La question de la manière – cette mesure personnelle de l’écriture, conquise au terme des quatre premiers recueils – ne se distingue pas chez lui de la question de la culture, et réciproquement.
Hippo signaling determines the number of venous pole cells that originate from the anterior lateral plate mesoderm in zebrafish
Authors: Fukui Hajime , Miyazaki Takahiro , Chow Renee Wei-Yan , Ishikawa Hiroyuki , Nakajima Hiroyuki , Vermot Julien , Mochizuki Naoki
Published: May 2018

The differentiation of the lateral plate mesoderm cells into heart field cells constitutes a critical step in the development of cardiac tissue and the genesis of functional cardiomyocytes. Hippo signaling controls cardiomyocyte proliferation, but the role of Hippo signaling during early cardiogenesis remains unclear. Here, we show that Hippo signaling regulates atrial cell number by specifying the developmental potential of cells within the anterior lateral plate mesoderm (ALPM), which are incorporated into the venous pole of the heart tube and ultimately into the atrium of the heart. We demonstrate that Hippo signaling acts through large tumor suppressor kinase 1/2 to modulate BMP signaling and the expression of hand2, a key transcription factor that is involved in the differentiation of atrial cardiomyocytes. Collectively, these results demonstrate that Hippo signaling defines venous pole cardiomyocyte number by modulating both the number and the identity of the ALPM cells that will populate the atrium of the heart.
Cognitive regulation alters social and dietary choice by changing attribute representations in domain-general and domain-specific brain circuits
Authors: Tusche Anita , Hutcherson Cendri A
Published: May 2018

Are some people generally more successful using cognitive regulation or does it depend on the choice domain? Why? We combined behavioral computational modeling and multivariate decoding of fMRI responses to identify neural loci of regulation-related shifts in value representations across goals and domains (dietary or altruistic choice). Surprisingly, regulatory goals did not alter integrative value representations in the ventromedial prefrontal cortex, which represented all choice-relevant attributes across goals and domains. Instead, the dorsolateral prefrontal cortex (DLPFC) flexibly encoded goal-consistent values and predicted regulatory success for the majority of choice-relevant attributes, using attribute-specific neural codes. We also identified domain-specific exceptions: goal-dependent encoding of prosocial attributes localized to precuneus and temporo-parietal junction (not DLPFC). Our results suggest that cognitive regulation operated by changing specific attribute representations (not integrated values). Evidence of domain-general and domain-specific neural loci reveals important divisions of labor, explaining when and why regulatory success generalizes (or doesn’t) across contexts and domains.
Social interaction-induced activation of RNA splicing in the amygdala of microbiome-deficient mice
Authors: Stilling Roman M , Moloney Gerard M , Ryan Feargal J , Hoban Alan E , Bastiaanssen Thomaz FS , Shanahan Fergus , Clarke Gerard , Claesson Marcus J , Dinan Timothy G , Cryan John F
Published: May 2018

Social behaviour is regulated by activity of host-associated microbiota across multiple species. However, the molecular mechanisms mediating this relationship remain elusive. We therefore determined the dynamic, stimulus-dependent transcriptional regulation of germ-free (GF) and GF mice colonised post weaning (exGF) in the amygdala, a brain region critically involved in regulating social interaction. In GF mice the dynamic response seen in controls was attenuated and replaced by a marked increase in expression of splicing factors and alternative exon usage in GF mice upon stimulation, which was even more pronounced in exGF mice. In conclusion, we demonstrate a molecular basis for how the host microbiome is crucial for a normal behavioural response during social interaction. Our data further suggest that social behaviour is correlated with the gene-expression response in the amygdala, established during neurodevelopment as a result of host-microbe interactions. Our findings may help toward understanding neurodevelopmental events leading to social behaviour dysregulation, such as those found in autism spectrum disorders (ASDs).
Rem2 stabilizes intrinsic excitability and spontaneous firing in visual circuits
Authors: Moore Anna R , Richards Sarah E , Kenny Katelyn , Royer Leandro , Chan Urann , Flavahan Kelly , Van Hooser Stephen D , Paradis Suzanne
Published: May 2018

Sensory experience plays an important role in shaping neural circuitry by affecting the synaptic connectivity and intrinsic properties of individual neurons. Identifying the molecular players responsible for converting external stimuli into altered neuronal output remains a crucial step in understanding experience-dependent plasticity and circuit function. Here, we investigate the role of the activity-regulated, non-canonical Ras-like GTPase Rem2 in visual circuit plasticity. We demonstrate that Rem2-/- mice fail to exhibit normal ocular dominance plasticity during the critical period. At the cellular level, our data establish a cell-autonomous role for Rem2 in regulating intrinsic excitability of layer 2/3 pyramidal neurons, prior to changes in synaptic function. Consistent with these findings, both in vitro and in vivo recordings reveal increased spontaneous firing rates in the absence of Rem2. Taken together, our data demonstrate that Rem2 is a key molecule that regulates neuronal excitability and circuit function in the context of changing sensory experience.
Metabolic interactions between dynamic bacterial subpopulations
Authors: Rosenthal Adam Z , Qi Yutao , Hormoz Sahand , Park Jin , Li Sophia Hsin-Jung , Elowitz Michael B
Published: May 2018

Individual microbial species are known to occupy distinct metabolic niches within multi-species communities. However, it has remained largely unclear whether metabolic specialization can similarly occur within a clonal bacterial population. More specifically, it is not clear what functions such specialization could provide and how specialization could be coordinated dynamically. Here, we show that exponentially growing Bacillus subtilis cultures divide into distinct interacting metabolic subpopulations, including one population that produces acetate, and another population that differentially expresses metabolic genes for the production of acetoin, a pH-neutral storage molecule. These subpopulations exhibit distinct growth rates and dynamic interconversion between states. Furthermore, acetate concentration influences the relative sizes of the different subpopulations. These results show that clonal populations can use metabolic specialization to control the environment through a process of dynamic, environmentally-sensitive state-switching.
Microglial transglutaminase-2 drives myelination and myelin repair via GPR56/ADGRG1 in oligodendrocyte precursor cells
Authors: Giera Stefanie , Luo Rong , Ying Yanqin , Ackerman Sarah D , Jeong Sung-Jin , Stoveken Hannah M , Folts Christopher J , Welsh Christina A , Tall Gregory G , Stevens Beth , Monk Kelly R , Piao Xianhua
Published: May 2018

In the central nervous system (CNS), myelin formation and repair are regulated by oligodendrocyte (OL) lineage cells, which sense and integrate signals from their environment, including from other glial cells and the extracellular matrix (ECM). The signaling pathways that coordinate this complex communication, however, remain poorly understood. The adhesion G protein-coupled receptor ADGRG1 (also known as GPR56) is an evolutionarily conserved regulator of OL development in humans, mice, and zebrafish, although its activating ligand for OL lineage cells is unknown. Here, we report that microglia-derived transglutaminase-2 (TG2) signals to ADGRG1 on OL precursor cells (OPCs) in the presence of the ECM protein laminin and that TG2/laminin-dependent activation of ADGRG1 promotes OPC proliferation. Signaling by TG2/laminin to ADGRG1 on OPCs additionally improves remyelination in two murine models of demyelination. These findings identify a novel glia-to-glia signaling pathway that promotes myelin formation and repair, and suggest new strategies to enhance remyelination.
Exportin Crm1 is repurposed as a docking protein to generate microtubule organizing centers at the nuclear pore
Authors: Bao Xun X , Spanos Christos , Kojidani Tomoko , Lynch Eric M , Rappsilber Juri , Hiraoka Yasushi , Haraguchi Tokuko , Sawin Kenneth E
Published: May 2018

Non-centrosomal microtubule organizing centers (MTOCs) are important for microtubule organization in many cell types. In fission yeast Schizosaccharomyces pombe, the protein Mto1, together with partner protein Mto2 (Mto1/2 complex), recruits the γ-tubulin complex to multiple non-centrosomal MTOCs, including the nuclear envelope (NE). Here, we develop a comparative-interactome mass spectrometry approach to determine how Mto1 localizes to the NE. Surprisingly, we find that Mto1, a constitutively cytoplasmic protein, docks at nuclear pore complexes (NPCs), via interaction with exportin Crm1 and cytoplasmic FG-nucleoporin Nup146. Although Mto1 is not a nuclear export cargo, it binds Crm1 via a nuclear export signal-like sequence, and docking requires both Ran in the GTP-bound state and Nup146 FG repeats. In addition to determining the mechanism of MTOC formation at the NE, our results reveal a novel role for Crm1 and the nuclear export machinery in the stable docking of a cytoplasmic protein complex at NPCs.
Covalent linkage of the DNA repair template to the CRISPR-Cas9 nuclease enhances homology-directed repair
Authors: Savic Natasa , Ringnalda Femke CAS , Lindsay Helen , Berk Christian , Bargsten Katja , Li Yizhou , Neri Dario , Robinson Mark D , Ciaudo Constance , Hall Jonathan , Jinek Martin , Schwank Gerald
Published: May 2018

The CRISPR-Cas9 targeted nuclease technology allows the insertion of genetic modifications with single base-pair precision. The preference of mammalian cells to repair Cas9-induced DNA double-strand breaks via error-prone end-joining pathways rather than via homology-directed repair mechanisms, however, leads to relatively low rates of precise editing from donor DNA. Here we show that spatial and temporal co-localization of the donor template and Cas9 via covalent linkage increases the correction rates up to 24-fold, and demonstrate that the effect is mainly caused by an increase of donor template concentration in the nucleus. Enhanced correction rates were observed in multiple cell types and on different genomic loci, suggesting that covalently linking the donor template to the Cas9 complex provides advantages for clinical applications where high-fidelity repair is desired.
Epigenetic drift of H3K27me3 in aging links glycolysis to healthy longevity in Drosophila
Authors: Ma Zaijun , Wang Hui , Cai Yuping , Wang Han , Niu Kongyan , Wu Xiaofen , Ma Huanhuan , Yang Yun , Tong Wenhua , Liu Feng , Liu Zhandong , Zhang Yaoyang , Liu Rui , Zhu Zheng-Jiang , Liu Nan
Published: May 2018

Epigenetic alteration has been implicated in aging. However, the mechanism by which epigenetic change impacts aging remains to be understood. H3K27me3, a highly conserved histone modification signifying transcriptional repression, is marked and maintained by Polycomb Repressive Complexes (PRCs). Here, we explore the mechanism by which age-modulated increase of H3K27me3 impacts adult lifespan. Using Drosophila, we reveal that aging leads to loss of fidelity in epigenetic marking and drift of H3K27me3 and consequential reduction in the expression of glycolytic genes with negative effects on energy production and redox state. We show that a reduction of H3K27me3 by PRCs-deficiency promotes glycolysis and healthy lifespan. While perturbing glycolysis diminishes the pro-lifespan benefits mediated by PRCs-deficiency, transgenic increase of glycolytic genes in wild-type animals extends longevity. Together, we propose that epigenetic drift of H3K27me3 is one of the molecular mechanisms that contribute to aging and that stimulation of glycolysis promotes metabolic health and longevity.
A cerebellar substrate for cognition evolved multiple times independently in mammals
Authors: Smaers Jeroen B , Turner Alan H , Gómez-Robles Aida , Sherwood Chet C
Published: May 2018

Given that complex behavior evolved multiple times independently in different lineages, a crucial question is whether these independent evolutionary events coincided with modifications to common neural systems. To test this question in mammals, we investigate the lateral cerebellum, a neurobiological system that is novel to mammals, and is associated with higher cognitive functions. We map the evolutionary diversification of the mammalian cerebellum and find that relative volumetric changes of the lateral cerebellar hemispheres (independent of cerebellar size) are correlated with measures of domain-general cognition in primates, and are characterized by a combination of parallel and convergent shifts towards similar levels of expansion in distantly related mammalian lineages. Results suggest that multiple independent evolutionary occurrences of increased behavioral complexity in mammals may at least partly be explained by selection on a common neural system, the cerebellum, which may have been subject to multiple independent neurodevelopmental remodeling events during mammalian evolution.
FBXL19 recruits CDK-Mediator to CpG islands of developmental genes priming them for activation during lineage commitment
Authors: Dimitrova Emilia , Kondo Takashi , Feldmann Angelika , Nakayama Manabu , Koseki Yoko , Konietzny Rebecca , Kessler Benedikt M , Koseki Haruhiko , Klose Robert J
Published: May 2018

CpG islands are gene regulatory elements associated with the majority of mammalian promoters, yet how they regulate gene expression remains poorly understood. Here, we identify FBXL19 as a CpG island-binding protein in mouse embryonic stem (ES) cells and show that it associates with the CDK-Mediator complex. We discover that FBXL19 recruits CDK-Mediator to CpG island-associated promoters of non-transcribed developmental genes to prime these genes for activation during cell lineage commitment. We further show that recognition of CpG islands by FBXL19 is essential for mouse development. Together this reveals a new CpG island-centric mechanism for CDK-Mediator recruitment to developmental gene promoters in ES cells and a requirement for CDK-Mediator in priming these developmental genes for activation during cell lineage commitment.
Practice Area Intentions of Graduates of Colleges of Osteopathic Medicine: What Role Does Debt Play?
Authors: Richards Jesse R. , Scheckel Caleb J. , Kunz Matt , Newman Jessica R. , Poole Kenneth G. , Mi Lanyu
Published: May 2018

Context

Enrollment in colleges of osteopathic medicine continues to increase, as does the need for physicians practicing in underserved areas. The cost of osteopathic medical education is substantial, with students often incurring debt of $200,000 or more. It is unclear whether practice patterns of new graduates will be affected by debt-to-income ratios.

Objective

To determine whether the intended practice location of graduates of colleges of osteopathic medicine is associated with medical education debt.

Methods

Using data from the American Association of Colleges of Osteopathic Medicine's annual survey to graduates of colleges of osteopathic medicine, the authors focused on graduates’ intention to practice in an underserved area, the amount of debt incurred, and plans to enter a loan-repayment program. Survey data from 2007, 2010, 2013, and 2016 were analyzed.

Results

From 2007 to 2016, the percentage of graduates who intended to practice in underserved areas increased (27.5% to 35.3%, respectively). Graduates with the most debt intended to practice in underserved areas at a higher percentage than those with the least amount of debt, and they also planned on using loan-repayment programs at a higher rate.

Conclusion

There is a strong association among the intention to practice in an underserved area, high debt load, and intention to use a loan-repayment program. Therefore, the osteopathic medical community should support increased access to loan-repayment programs to help its graduates surmount economic and social barriers to providing care in underserved areas.
Sorting nexin-1 is a candidate tumor suppressor and potential prognostic marker in gastric cancer
Authors: Zhan Xiao-Yong , Zhang Yaqiong , Zhai Ertao , Zhu Qing-Yi , He Yulong
Published: May 2018

Sorting nexin-1 (SNX1) is an important functional protein in cell endocytosis, efflux, protein sorting, cell signal transduction, etc; however, the expression, the role and clinical relevance of SNX1 have not been investigated in gastric cancer (GC). In this study, we first performed a bioinformatics investigation using the data obtained from The Cancer Genome Atlas (TCGA) database. The result showed that SNX1 mRNA levels were significantly lower in GC tissues than in paracancerous tissues. In a study of 150 cases of GC, including 60 cases with paired paracancerous and cancer tissues and 90 cases with detailed follow-up information, SNX1 expression was analyzed by immunohistochemistry. Our study on paired paracancerous and cancer tissues showed that SNX1 protein expression remarkably decreased in GC tissues (50/60, 83.33%). A study on 90 patients with detailed follow-up information showed that tumors with higher SNX1 protein level were correlated with better clinicopathologic stages (p = 0.0285), nodal status (p = 0.0286), smaller tumor sizes (p = 0.0294) and a better survival rate in patients with GC (p = 0.0245). Univariate analysis of the 90 patients with GC showed that low-level SNX1 was significantly correlated with decreased overall survival of GC patients (p = 0.008), and associated with a relatively higher cumulative hazard of death. Exogenous expression of SNX1 inhibited the growth, migration, invasion and promoted the apoptosis and enhanced the sensitivity of GC cells to the chemotherapeutic drug 5-Fluorouracil (5-Fu) in vitro, while knockdown of SNX1 by short hairpin RNA (shRNA) significantly promoted the growth, migration, invasion and reduced the apoptosis and the sensitivity of GC cells to 5-Fu. SNX1 also showed to influence the levels of epithelial-mesenchymal transition markers including Vimentin, Snail, and E-cadherin in GC cells in vitro. Taken together, we propose here that SNX1 serves as a tumor suppressor and prognostic marker that reduces tumor cell malignancy for GC.
Changes in species abundance after seven years of elevated atmospheric CO2 and warming in a Subarctic birch forest understorey, as modified by rodent and moth outbreaks
Authors: Svensson Brita M. , Carlsson Bengt Å. , Melillo Jerry M.
Published: May 2018

A seven-year long, two-factorial experiment using elevated temperatures (5 °C) and CO2 (concentration doubled compared to ambient conditions) designed to test the effects of global climate change on plant community composition was set up in a Subarctic ecosystem in northernmost Sweden. Using point-frequency analyses in permanent plots, an increased abundance of the deciduous Vaccinium myrtillus, the evergreens V. vitis-idaea and Empetrum nigrum ssp. hermaphroditum and the grass Avenella flexuosa was found in plots with elevated temperatures. We also observed a possibly transient community shift in the warmed plots, from the vegetation being dominated by the deciduous V. myrtillus to the evergreen V. vitis-idaea. This happened as a combined effect of V. myrtillus being heavily grazed during two events of herbivore attack—one vole outbreak (Clethrionomys rufocanus) followed by a more severe moth (Epirrita autumnata) outbreak that lasted for two growing seasons—producing a window of opportunity for V. vitis-idaea to utilize the extra light available as the abundance of V. myrtillus decreased, while at the same time benefitting from the increased growth in the warmed plots. Even though the effect of the herbivore attacks did not differ between treatments they may have obscured any additional treatment effects. This long-term study highlights that also the effects of stochastic herbivory events need to be accounted for when predicting future plant community changes.
Two new species of Acromastigum (Lepidoziaceae: Jungermanniopsida) from Queensland, Australia
Authors: Renner Matt A.M , Wilson Trevor
Published: May 2018

As a result of fieldwork on Cape York Peninsula, and ongoing revision of type specimens in lieu of the recent revision of Australian Acromastigum, two new species are described. Acromastigum carcinum represents a newly discovered species, currently known only from one location within the Jardine River National Park. The lowland and tropical monsoonal habitat of this species is highly unusual within the genus, and hints at the existence of a distinct, if species poor, bryofloristic element within tropical monsoon lowland habitats. Acromastigum implexum has been long recognised in Australia under the name A. echinatiforme, however comparison with the original material of that species confirms Australian plants represent a distinct species. Acromastigum implexum inhabits tropical montane rainforest habitats. Both species are currently known only from Australia, but both, particularly A. carcinum, may occur in similar habitats overseas.
“НЕОТМИРАЮЩЕЕ ГОСУДАРСТВО”: ЧТО МЕШАЕТ РЕФОРМАМ ГОСУПРАВЛЕНИЯ В РОССИИ, "Общественные науки и современность"
Authors: ПАРЦВАНИЯ Вахтанг Русланович
Published: May 2018

В статье на основе классического положения К. Маркса и Ф. Энгельса об отмирании государства сделана попытка раскрыть концептуальные причины, задающие пределы и ограничения ­реформам российско-советского бюрократического государства. Автор обосновывает в качестве фундаментальной причины провала реформ - хронические представления о враждебности западных стран по отношению к России, закрепившиеся в сознании основной массы политиков, бюрократов и общественности. Эти представления уходят корнями в российскую историю и продолжают логику идеологических воззрений советского политико-бюрократического класса, предопределившую неудовлетворительное состояние российского государственного аппарата. Их “демонтаж” в массовом сознании современного российского общества представляется автору важнейшим предварительным условием успешной реализации новой волны давно назревших реформ госуправления в России.
ОСНОВНЫЕ ПОДХОДЫ К ОБЪЯСНЕНИЮ ПРОБЛЕМЫ СОЦИАЛЬНО-ЭКОНОМИЧЕСКОГО РАЗВИТИЯ В ОБЩЕСТВЕННЫХ НАУКАХ, "Общественные науки и современность"
Authors: ТИТОВ Владимир Николаевич
Published: May 2018

В статье критически рассмотрены основные теоретические подходы к изучению проблемы ­неравномерности социально-экономического развития различных обществ. Выделяются три наиболее влиятельных теоретико-методологических подхода в данной сфере обществознания: институциональный, структурный, социокультурный. Показаны преимущества и ограничения, связанные с их использованием при объяснении причин и механизмов, влияющих на процессы и динамику социально-экономического развития. Делается вывод, что успешное продвижение по пути дальнейшего изучения факторов социально-экономического развития зависит от способности ­создания концептуального подхода, в рамках которого были бы определены взаимосвязи между институциональными, структурными и культурными параметрами, с одной стороны, и контингентными переменными - с другой.
НАУКА ТОЛПЫ И НАУКА ГРАЖДАН*, "Общественные науки и современность"
Authors: ЕГЕРЕВ Сергей Викторович
Published: May 2018

В статье рассматривается современное состояние распределенных исследовательских проектов. Уточняется терминология, относящаяся к разновидностям проектов: научному краудсорсингу, науке толпы, науке граждан и другим. Обобщается опыт организации и сопровождения распределенных исследований. Отмечены ключевые аспекты менеджмента науки толпы и науки граждан. Показано, каким образом современные информационные технологии способствуют развитию новых направлений распределенных исследований. Уделено внимание достижениям распределенных исследовательских проектов в области гуманитарных наук.
РИТОРИЧЕСКАЯ АРГУМЕНТАЦИЯ И ПОЛИТИЧЕСКАЯ СИМВОЛИЗАЦИЯ, "Общественные науки и современность"
Authors: Мусихин Глеб Иванович
Published: May 2018

Анализируется политическая аргументация как механизм выработки политических смыслов, отображающихся и артикулирующихся в ходе политической делиберации. Специфический характер такого механизма делает неопределенность развития субстантивным свойством политики. Язык политической аргументации рассматривается не как отражение политических процессов, а как само политическое коммуникативное действие. Комплекс риторических приемов концептуализируется в качестве способного к самостоятельному смыслообразованию механизмов политики, который может производить новые идеи и убеждения. В политическом контексте категории выступают не элементами мышления, а явлениями риторики. В ходе публичной делиберации категории служат не формообразующей силой мысли, а объектами обсуждения и аргументации. Целесо­образнее оперировать понятием риторической политической ситуации как явлением политической реальности. Политическая коммуникация в таких ситуациях, как правило, будет провоцировать эпистемологические и нравственные дилеммы, делающие нормативную и утилитарную оценку неоднозначной, а потому неконвенциональной. Однако особенность политической символической реальности в том, что такая оценка обязательно последует.
Cross‐cultural differences in object recognition: Comparing asylum seekers from Sub‐Saharan Africa and a matched Western European control group
Authors: de Bruïne Gabi , Vredeveldt Annelies , van Koppen Peter J.
Published: May 2018

Nowadays, more and more people report about their memories in cross‐cultural contexts. In international criminal settings and asylum procedures, object recognition tests can provide valuable information, for example, about weapons used during a crime or landmarks from the claimed region of origin. This study was the first to compare object recognition performance by asylum seekers from Sub‐Saharan Africa to a matched Western European control group. African participants performed worse than European participants on perceptual tests involving transformations from two‐ to three‐dimensional representations, but both groups performed equally well on an object recognition test that involved transformation from three‐ to two‐dimensional representations. However, African participants were significantly more likely to respond “yes” on the recognition test (i.e., an acquiescence response style) than European participants. Our findings elucidate cultural differences in responding on an object recognition test. Judges, juries, and immigration officials would be wise to take these differences into account when evaluating recognition performance in cross‐cultural contexts.