bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of RNA-seq normalization methods using challenging datasets
Authors: Uebbing Severin 
Published: August 2018

AbstractRNA-seq is a powerful tool for both discovery and experimentation. Most RNA-seq studies rely on library normalization to compare samples or to reliably estimate quantitative gene expression levels. Over the years a number of RNA-seq normalization methods have been proposed. Review studies testing these methods have provided evidence that commonly used methods perform well in simple normalization tasks, but their performance in challenging normalization tasks has yet to be evaluated. Here I test RNA-seq normalization methods using two challenging normalization scenarios. My assessment reveals surprising shortcomings of some commonly used methods and identifies an underappreciated method as the most promising normalization strategy for common, yet challenging RNA-seq experiments.
Linking Darwin’s naturalisation hypothesis and Elton’s diversity–invasibility hypothesis in experimental grassland communities
Authors: Feng Yanhao , Fouqueray Timothée Donatien , van Kleunen Mark 
Published: August 2018

Abstract

Darwin’s naturalisation hypothesis posing that phylogenetic distance of alien species to native residents predicts invasion success, and Elton’s diversity–invasibility hypothesis posing that diversity of native communities confers resistance to invasion, are both rooted in ideas of species coexistence. Because the two hypotheses are inherently linked, the mechanisms underlying them may interact in driving the invasion success. Even so, these links and interactions have not been explicitly disentangled in one experimental study before.

To disentangle the links between the two hypotheses, we used 36 native grassland herbs to create greenhouse mesocosms with 90 grassland communities of different diversities, and introduced each of five herbaceous alien species as seeds and seedlings. We used phylogeny and four functional traits (plant height, specific leaf area, leaf size, and seed mass) to calculate different measures of phylogenetic and functional distance and diversity. Specifically, we tested how the alien–native distance (phylogenetic or functional) and the native diversity (phylogenetic or functional) affected each other in their effects on germination, seedling survival, growth, and reproduction of the aliens.

Overall, our results supported both hypotheses. Multivariate functional distance based on four traits jointly had stronger positive effects than phylogenetic distance and the univariate ones based on each trait separately. Moreover, the aliens were more successful if they were more competitive by being taller and having larger leaves with a lower SLA than the native residents. Univariate functional diversity based on each trait separately had stronger negative effects than phylogenetic and multivariate functional diversity. Most importantly, we found that the effects of alien–native phylogenetic and multivariate functional distance became stronger as diversity increased. Our analyses with single traits also showed that the strength of the effects of both alien–native hierarchical functional distances (indicative of competitive inequalities) and absolute functional distances (indicative of niche differences) increased at higher diversities, where competition is more severe.

Synthesis. Our study explicitly demonstrates for the first time how the mechanisms underlying the two classical invasion hypotheses interact in driving invasion success in grassland communities. This may help to explain some of the puzzling results of studies testing either of the two hypotheses.
Below‐ground plant traits influence tundra plant acquisition of newly thawed permafrost nitrogen
Authors: Hewitt Rebecca E. , Taylor D. Lee , Genet Hélène , McGuire A. David , Mack Michelle C. 
Published: August 2018

Abstract

The release of permafrost‐derived nitrogen (N) has the potential to fertilize tundra vegetation, which in turn may stimulate productivity and thus offset carbon (C) losses from thawing permafrost. Below‐ground plant traits may mediate ecosystem response to permafrost thaw and associated feedbacks to the atmosphere by differentially conferring access to deep, newly thawed permafrost N. Yet, identifying roots and quantifying root N uptake from deep, cold soils in complex plant communities has proved challenging to date.

We investigated plant acquisition of experimentally added 15N isotope tracer applied at the permafrost boundary in graminoid‐ and shrub‐dominated tundra at Eight Mile Lake, Alaska, when the thaw front was close to its maximum depth, simulating the release of newly thawed permafrost N. We used molecular tools to verify species and estimate biomass, nitrogen, and isotope pools.

Root biomass depth distributions follow an asymptotic relationship with depth, typical of other ecosystems. Few species had roots occurring close to the thaw front. Rubus chamaemorus, a short‐statured non‐mycorrhizal forb, and Carex bigelowii, a sedge, consistently had the deepest roots. Twenty‐four hours after isotope addition, we observed that deep‐rooted, non‐mycorrhizal species had the highest 15N enrichment values in their fine root tissue indicating that they access deep N late in the growing season when the thaw front is deepest. Deep‐rooted plants are therefore able to immediately take up newly thawed permafrost‐derived N. During the following growing season, herbaceous, non‐mycorrhizal plants allocated tracer above‐ground before woody, mycorrhizal plants. Ectomycorrhizal deciduous and ericoid mycorrhizal evergreen shrubs, by contrast, did not have immediate access to the deep N tracer and assimilated it into new foliar tissue gradually over the following growing season.

Synthesis. Graminoids and forbs that have immediate access to deep N represent a modest C sink compared to C emissions from thawing permafrost. However, the effects of deep N fertilization on shrubs over longer time‐scales may stimulate productivity and account for a more considerable N and C sink, thus constraining the permafrost C‐climate feedback.
Challenges of heterotopic ossification—Molecular background and current treatment strategies
Authors: Łęgosz Paweł , Drela Katarzyna , Pulik Łukasz , Sarzyńska Sylwia , Małdyk Paweł 
Published: August 2018

SummaryHeterotopic ossification (HO) is an abnormal formation of mature lamellar bone within extraskeletal soft tissues, such as muscles, tendons, and ligaments. This process is thought to be induced by inflammation associated with tissue injuries. HO is classified using two subtypes: resulting from injury or genetically inherited. HO formation is associated with polytrauma patients with traumatic brain injuries and spinal cord injuries. Moreover, HO is also considered to be a post‐operative risk factor in some orthopaedic procedures. In this review, we summarize our current understanding of the pathology of different types of HO and discuss its current and future therapies. Thus far, research has revealed cellular and molecular pathways leading to HO formation and proposed several possible mechanisms leading to HO and conserved signalling pathways common in the different HO subtypes. Non‐steroidal anti‐inflammatory drug treatment and localized low‐dose irradiation are currently the only available prophylactic treatments for HO. However, they are not always effective and do not target the osteogenic processes directly. New therapeutic strategies targeting the pathological processes of HO, such as bone morphogenetic protein (BMP) inhibitors like noggin, BMP type 1 receptor inhibitor, and nuclear retinoid acid receptor‐gamma (RARγ) agonists, are currently being investigated. In‐depth understanding of the HO pathological process could help to develop effective therapeutic strategies.
Pectic polysaccharides extracted from Rauvolfia verticillata (Lour.) Baill. var. hainanensis Tsiang ameliorate ulcerative colitis via regulating the MAPKs and NF‐κB pathways in dendritic cells
Authors: Miao Xin‐Pu , Sun Xiao‐Ning , Li Qiong‐Si , Cui Lu‐Jia , Wang Xuan‐Yu , Zhuang Gui‐Feng , Deng Tao‐Zhi 
Published: August 2018

SummaryThis study was to investigate the effects and mechanisms of pectic polysaccharides (PP) extracted from Rauvolfia verticillata (Lour.) Baill. var. hainanensis Tsiang on dextran sulphate sodium (DSS)‐induced ulcerative colitis (UC). Eighty female BALB/c mice were randomly divided into four groups: Control, DSS, DSS + salicylazosulfapyridine (SASP), and DSS+ PP. The disease activity index (DAI), overall physical activity, and blood stool were monitored daily to evaluate severity of UC. Histological scores of the colon were observed. The expression of nuclear factor κB (NF‐κB) and mitogen‐activated protein kinase (MAPKs) pathways in colon tissues and bone marrow‐derived dendritic cells (DCs) was assessed by western blot, immunohistochemistry, electrophoretic mobility shift assay (EMSA) and real time polymerase chain reaction (RT‐PCR). Cytokines were measured by enzyme‐linked immunosorbent assay (ELISA). The overall physical activity, DAI and histological scores decreased in DSS+SASP and DSS+PP groups, compared with the DSS‐alone group. Also, tumour necrosis factor α (TNF‐α) and interleukin 6 (IL‐6) reduced significantly while the expression of IκBα was up‐regulated, extracellular signal‐regulated kinase (ERK), Jun N‐terminal kinase (JNK) and p38 were activated, in DSS+SASP and DSS+PP groups. PP inhibited activation of MAPKs and NF‐κB pathways in the bone‐marrow‐derived DCs. In conclusion, PP significantly ameliorated murine DSS‐induced UC model, via regulation of MAPKs and NF‐κB pathways in DCs.
ARAP2 inhibits Akt independently of its effects on focal adhesions
Authors: Luo Ruibai , Chen Pei‐Wen , Kuo Jean‐Cheng , Jenkins Lisa , Jian Xiaoying , Waterman Clare M. , Randazzo Paul A. 
Published: August 2018

Background InformationARAP2, an Arf GTPase‐activating protein (Arf GAP) that binds to adaptor protein with PH domain, PTB domain and leucine zipper motifs 1 (APPL1), regulates focal adhesions (FAs). APPL1 affects FA dynamics by regulating Akt. Here, we tested the hypothesis that ARAP2 affects FAs in part by regulating Akt through APPL1.ResultsWe found that ARAP2 controlled FA dynamics dependent on its enzymatic Arf GAP activity. In some cells, ARAP2 also regulated phosphoAkt (pAkt) levels. However, ARAP2 control of FAs did not require Akt and conversely, the effects on pAkt were independent of FAs. Reducing ARAP2 expression reduced the size and number of FAs in U118, HeLa and MDA‐MB‐231 cells. Decreasing ARAP2 expression increased pAkt in U118 cells and HeLa cells and overexpressing ARAP2 decreased pAkt in U118 cells; in contrast, ARAP2 had no effect on pAkt in MDA‐MB‐231 cells. An Akt inhibitor did not block the effect of reduced ARAP2 on FAs in U118. Furthermore, the effect of ARAP2 on Akt did not require Arf GAP activity, which is necessary for effects on FAs and integrin traffic. Altering FAs by other means did not induce the same changes in pAkt as those seen by reducing ARAP2 in U118 cells. In addition, we discovered that ARAP2 and APPL1 had co‐ordinated effects on pAkt in U118 cells. Reduced APPL1 expression, as for ARAP2, increased pAkt in U118 and the effect of reduced APPL1 expression was reversed by overexpressing ARAP2. Conversely, the effect of reduced ARAP2 expression was reversed by overexpressing APPL1. ARAP2 is an Arf GAP that has previously been reported to affect FAs by regulating Arf6 and integrin trafficking and to bind to the adaptor proteins APPL1. Here, we report that ARAP2 suppresses pAkt levels in cells co‐ordinately with APPL1 and independently of GAP activity and its effect on the dynamic behaviour of FAs.ConclusionsWe conclude that ARAP2 affects Akt signalling in some cells by a mechanism independent of FAs or membrane traffic.SignificanceOur results highlight an Arf GAP‐independent function of ARAP2 in regulating Akt activity and distinguish the effect of ARAP2 on Akt from that on FAs and integrin trafficking, which requires regulation of Arf6.
The potential role for infections in the pathogenesis of autoimmune Addison’s disease
Authors: Hellesen A , Bratland E 
Published: August 2018

Summary
Autoimmune Addison’s disease (AAD), or primary adrenocortical insufficiency, is a classical organ-specific autoimmune disease with 160 years of history. AAD is remarkably homogeneous with one major dominant self-antigen, the cytochrome P450 21-hydroxylase enzyme, which is targeted by both autoantibodies and autoreactive T cells. Like most autoimmune diseases, AAD is thought to be caused by an unfortunate combination of genetic and environmental factors. While the number of genetic associations with AAD is increasing, almost nothing is known about environmental factors. A major environmental factor commonly proposed for autoimmune diseases, based partly on experimental and clinical data and partly on shared pathways between anti-viral immunity and autoimmunity, is viral infections. However, there are few reports associating viral infections to AAD, and it has proved difficult to establish which immunological processes that could link any viral infection with the initiation or progression of AAD. In this review, we will summarize the current knowledge on the underlying mechanisms of AAD and take a closer look on the potential involvement of viruses.
Social defeat stress: Mechanisms underlying the increase in rewarding effects of drugs of abuse
Authors: Montagud‐Romero Sandra , Blanco‐Gandía Maria Carmen , Reguilón Marina D. , Ferrer‐Pérez Carmen , Ballestín Raul , Miñarro Jose , Rodríguez‐Arias Marta 
Published: August 2018

AbstractSocial interaction is known to be the main source of stress in human beings, which explains the translational importance of this research in animals. Evidence reported over the last decade has revealed that, when exposed to social defeat experiences (brief episodes of social confrontations during adolescence and adulthood), the rodent brain undergoes remodeling and functional modifications, which in turn lead to an increase in the rewarding and reinstating effects of different drugs of abuse. The mechanisms by which social stress cause changes in the brain and behavior are unknown, and so the objective of this review is to contemplate how social defeat stress induces long‐lasting consequences that modify the reward system. First of all, we will describe the most characteristic results of the short‐ and long‐term consequences of social defeat stress on the rewarding effects of drugs of abuse such as psychostimulants and alcohol. Secondly, and throughout the review, we will carefully assess the neurobiological mechanisms underlying these effects, including changes in the dopaminergic system, corticotrophin releasing factor signaling, epigenetic modifications and the neuroinflammatory response. To conclude, we will consider the advantages and disadvantages and the translational value of the social defeat stress model, and will discuss challenges and future directions.
Implementation of deep neural networks to count dopamine neurons in substantia nigra
Authors: Penttinen Anna‐Maija , Parkkinen Ilmari , Blom Sami , Kopra Jaakko , Andressoo Jaan‐Olle , Pitkänen Kari , Voutilainen Merja H. , Saarma Mart , Airavaara Mikko 
Published: August 2018

AbstractUnbiased estimates of neuron numbers within substantia nigra are crucial for experimental Parkinson's disease models and gene‐function studies. Unbiased stereological counting techniques with optical fractionation are successfully implemented, but are extremely laborious and time‐consuming. The development of neural networks and deep learning has opened a new way to teach computers to count neurons. Implementation of a programming paradigm enables a computer to learn from the data and development of an automated cell counting method. The advantages of computerized counting are reproducibility, elimination of human error and fast high‐capacity analysis. We implemented whole‐slide digital imaging and deep convolutional neural networks (CNN) to count substantia nigra dopamine neurons. We compared the results of the developed method against independent manual counting by human observers and validated the CNN algorithm against previously published data in rats and mice, where tyrosine hydroxylase (TH)‐immunoreactive neurons were counted using unbiased stereology. The developed CNN algorithm and fully cloud‐embedded Aiforia™ platform provide robust and fast analysis of dopamine neurons in rat and mouse substantia nigra.
The role of fibroblast growth factor 2 in drug addiction
Authors: Even‐Chen Oren , Barak Segev 
Published: August 2018

AbstractFibroblast growth factor 2 (FGF2) is a member of the FGF‐family, which consists of 22 members, with four known FGF receptors (five in humans). Over the last 30 years, FGF2 has been extensively studied for its role in cell proliferation, differentiation, growth, survival and angiogenesis during development, as well as for its role in adult neurogenesis and regenerative plasticity. Over the past decade, FGF2 has been implicated in learning and memory, as well as in several neuropsychiatric disorders, including anxiety, stress, depression and drug addiction. In this review, we present accumulating evidence indicating the involvement of FGF2 in neuroadaptations caused by drugs of abuse, namely, amphetamine, cocaine, nicotine and alcohol. Moreover, evidence suggests that FGF2 is a positive regulator of alcohol and drug‐related behaviors. Thus, although additional studies are yet required, we suggest that reducing FGF2 activity may provide a novel therapeutic approach for substance use disorders.
The neural correlates of trustworthiness evaluations of faces and brands: Implications for behavioral and consumer neuroscience
Authors: Javor Andrija , Kindermann Harald , Koschutnig Karl , Ischebeck Anja 
Published: August 2018

AbstractWhen we buy a product of a brand, we trust the brand to provide good quality and reliability. Therefore, trust plays a major role in consumer behavior. It is unclear, however, how trust in brands is processed in the brain and whether it is processed differently from interpersonal trust. In this study, we used fMRI to investigate the neural correlates of interpersonal and brand trust by comparing the brain activation patterns during explicit trustworthiness judgments of faces and brands. Our results showed that while there were several brain areas known to be linked to trustworthiness evaluations, such as the amygdalae, more active in trustworthiness judgments when compared to a control task (familiarity judgment) for faces, no such difference was found for brands. Complementary ROI analysis revealed that the activation of both amygdalae was strongest for faces in the trustworthiness judgments. The direct comparison of the brain activation patterns during the trustworthiness evaluations between faces and brands in this analysis showed that trustworthiness judgments of faces activated the orbitofrontal cortex, another region that was previously linked to interpersonal trust, more strongly than trustworthiness judgments of brands. Further, trustworthiness ratings of faces, but not brands, correlated with activation in the orbitofrontal cortex. Our results indicate that the amygdalae, as well as the orbitofrontal cortex, play a prominent role in interpersonal trust (faces), but not in trust for brands. It is possible that this difference is due to brands being processed as cultural objects rather than as having human‐like personality characteristics.
FoxO1 enhances differentiation and apoptosis in human primary keratinocytes
Authors: Shi Ge , Liao Pei‐Yu , Cai Xiao‐Lin , Pi Xiao‐Xue , Zhang Man‐Feng , Li Shi‐Jie , Quan Juan‐Hua , Fan Yi‐Ming 
Published: August 2018

AbstractForkhead box‐O1 (FoxO1) is a key nutrient‐ and growth factor‐dependent regulator of metabolism, but its functional role in human primary keratinocytes (HPKs) is less known. To investigate the role of FoxO1 in HPKs and effect of insulin‐like growth factor 1 (IGF‐1) and isotretinoin on FoxO1 expression, HPKs were treated with 1.2 mmol/L calcium chloride, 1‐20 ng/mL IGF‐1 and 0.1‐10 μmol/L isotretinoin. Recombinant adenovirus expressing FoxO1 or FKHR shRNA lentivirus transfection was introduced to upregulate or silence FoxO1 expression. Epidermal FoxO1 immunostaining was lower in acne lesion than in normal skin. FoxO1 overexpression induced involucrin expression, G2/M arrest and apoptosis but suppressed proliferation, while FoxO1 silencing decreased involucrin expression but increased proliferation, S phase and viable cells in HPKs. IGF‐1 downregulated FoxO1 and involucrin but upregulated p‐Akt expression in HPKs, which was blocked by pretreatment with LY294002. Isotretinoin enhanced FoxO1, p53 and p21 but inhibited p‐FoxO1 and involucrin expression in HPKs. These results demonstrate that FoxO1 promotes differentiation and apoptosis in HPKs. IGF‐1 may reduce keratinocyte differentiation through PI3K/Akt/FoxO1 pathway, while isotretinoin can reinforce FoxO1 expression. FoxO1 may be involved in acne pathogenesis and could serve as a potential therapeutic target.
Degradation of phosphate polymer polyP enhances lactic fermentation in mice
Authors: Nakamura Akihiro , Kawano Natsuko , Motomura Kei , Kuroda Akio , Sekiguchi Kiyoshi , Miyado Mami , Kang Woojin , Miyamoto Yoshitaka , Hanai Maito , Iwai Maki , Yamada Mitsutoshi , Hamatani Toshio , Saito Takakazu , Saito Hidekazu , Tanaka Mamoru , Umezawa Akihiro , Miyado Kenji 
Published: August 2018

AbstractIn bacteria, a polymer of inorganic phosphate (Pi) (inorganic polyphosphate; polyP) is enzymatically produced and consumed as an alternative phosphate donor for adenosine triphosphate (ATP) production to protect against nutrient starvation. In vertebrates, polyP has been dismissed as a “molecular fossil” due to the lack of any known physiological function. Here, we have explored its possible role by producing transgenic (TG) mice widely expressing Saccharomyces cerevisiae exopolyphosphatase 1 (ScPPX1), which catalyzes hydrolytic polyP degradation. TG mice were produced and displayed reduced mitochondrial respiration in muscles. In female TG mice, the blood concentration of lactic acid was enhanced, whereas ATP storage in liver and brain tissues was reduced significantly. Thus, we suggested that the elongation of polyP reduces the intracellular Pi concentration, suppresses anaerobic lactic acid production, and sustains mitochondrial respiration. Our results provide an insight into the physiological role of polyP in mammals, particularly in females.
Orientation‐dependent electrical property and domain configuration of Mn‐doped Pb(In0.5Nb0.5)O3–PbTiO3 single crystal
Authors: Qiao Huimin , He Chao , Wang Zujian , Li Xiuzhi , Liu Ying , Tailor Hamel , Long Xifa 
Published: August 2018

AbstractOrientation dependence of electrical properties and domain configurations of 8 mol% Mn‐doped rhombohedral PIN‐PT (0.68Pb(In0.5Nb0.5)O3–0.32Pb(Ti0.92Mn0.08)O3) rhombohedral single crystals were investigated with an emphasis on studying the variations of coercive field (EC), internal field (Ei) on domain patterns. Our results showed that for both [001] and [110]‐oriented samples, the coercive field and internal field decreased with temperature (T) increasing in rhombohedral phase, and a peak appeared above rhombohedral‐tetragonal phase transition temperature (TRT). The abnormal peaks between TRT and Curie temperature on EC‐T and Ei‐T plots are explained by taking into consideration the ferroelectric phase transition and variation of defect polarization, which provides assistant comprehension on the dynamic of defect dipoles during phase transition at high temperature. Bubble‐ and ribbon‐like domain patterns were observed in (001)‐ and (110)‐plane, respectively, and smaller value of short‐length correlation radius in (001)‐ plane indicates less aggregation of polar nanoregions in this crystallographic plane than that in (110)‐plane.