bluuebunny/crossref_metadata_2025 huggingface dataset:
Counterspaces for women of color in STEM higher education: Marginal and central spaces for persistence and success
Authors: Ong Maria , Smith Janet M. , Ko Lily T.
Published: August 2017

Counterspaces in science, technology, engineering, and mathematics (STEM) are often considered “safe spaces” at the margins for groups outside the mainstream of STEM education. The prevailing culture and structural manifestations in STEM have traditionally privileged norms of success that favor competitive, individualistic, and solitary practices—norms associated with White male scientists. This privilege extends to structures that govern learning and mark progress in STEM education that have marginalized groups that do not reflect the gender, race, or ethnicity conventionally associated with STEM mainstream success, thus necessitating spaces in which the effects of marginalization may be countered. Women of color is one such marginalized group. This article explores the struggles of women of color that threaten their persistence in STEM education and how those struggles lead them to search out or create counterspaces. It also examines the ways that counterspaces operate for women of color in STEM higher education, particularly how they function as havens from isolation and microaggressions. Using a framework of Critical Race Theory (CRT) and intersectionality theory and drawing on interview data from 39 women of color about their STEM higher education experiences, we describe five ways in which counterspaces operate: in peer‐to‐peer relationships; mentoring relationships; national STEM diversity conferences; STEM and non‐STEM campus student groups; and STEM departments. Whereas most research has discussed counterspaces as racially or ethnically homogeneous social groups of peers at the margins, our research found that counterspaces vary in terms of the race/ethnicity, gender, and power levels of participants. We found that counterspaces can be physical settings, as well as conceptual and ideological. Additionally, we identified counterspaces both at the margins and at the center of STEM departments. Thus, our research expands the existing understanding of the types and functions of counterspaces and broadens the definition of what locations can be and should be considered counterspaces. © 2017 The Authors.Journal of Research in Science TeachingPublished by Wiley Periodicals, Inc. on behalf of National Association for Research in Science Teaching. J Res Sci Teach 55: 206–245, 2018
Ancient and modern: hints of a core post‐transcriptional network driving chemotherapy resistance in ovarian cancer
Authors: Blagden Sarah , Abdel Mouti Mai , Chettle James
Published: August 2017

RNA‐binding proteins (RBPs) and noncoding (nc)RNAs (such as microRNAs, long ncRNAs, and others) cooperate within a post‐transcriptional network to regulate the expression of genes required for many aspects of cancer behavior including its sensitivity to chemotherapy. Here, using an RBP‐centric approach, we explore the current knowledge surrounding contributers to post‐transcriptional gene regulation (PTGR) in ovarian cancer and identify commonalities that hint at the existence of an evolutionarily conserved core PTGR network. This network regulates survival and chemotherapy resistance in the contemporary context of the cancer cell. There is emerging evidence that cancers become dependent on PTGR factors for their survival. Further understanding of this network may identify innovative therapeutic targets as well as yield crucial insights into the hard‐wiring of many malignancies, including ovarian cancer. WIREs RNA 2018, 9:e1432. doi: 10.1002/wrna.1432

This article is categorized under:

RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications

Translation > Translation Mechanisms

RNA in Disease and Development > RNA in Disease
CHADS2 and modified CHA2DS2‐VASc scores for the prediction of congestive heart failure in patients with nonvalvular atrial fibrillation
Authors: Koeda Yorihiko , Komatsu Takashi , Matsuura Yuki , Morioka Hidemi , Uchimura Yohei , Taguchi Yuya , Tanaka Kentaro , Kawakami Jun , Nakamura Marie , Takahashi Shuko , Takahashi Yuji , Naganuma Yujiro , Endo Hiroshi , Ito Tatsuro , Morino Yoshihiro , Nakamura Motoyuki
Published: August 2017

Background & purpose

We have conducted a retrospective observational study to analyze the correlation between the CHADS2 score, the modified CHA2DS2‐VASc (mCHA2DS2‐VASc) score, and the incidence of all‐cause death and congestive heart failure (CHF).

Methods

The study cohort consisted of 292 consecutive patients with nonvalvular atrial fibrillation (NVAF) admitted to our hospital from 2012 to 2014. Electronic medical records were used to confirm medical history including prior heart failure, hypertension, diabetes, stroke, and coronary disease. A follow‐up survey for all‐cause deaths and incidence of CHF was carried out from the baseline data to May 2015. We analyzed the correlation between each score and the endpoints using the Kaplan‐Meier method and the Cox proportional hazards model.

Result

During the follow up period (mean=1.6 years), 69 all‐cause deaths and 58 CHF events occurred in the cohort. There was no significant association between these scores and all‐cause death in our CHF cohort. The incidence of CHF significantly increased along with increased CHADS2 (p=0.018) or mCHA2DS2‐VASc scores (p=0.044). The hazard ratio (HR) for CHF after adjustment for drug treatment was obtained from a Cox proportional hazards model. The HRs for the CHADS2 and mCHA2DS2‐VASc scores were 1.38 (95% CI; 1.13–1.68) and 1.35 (95% CI; 1.24–1.59), respectively.

Conclusion

Calculation of the CHADS2 and mCHA2DS2‐VASc scores in order to evaluate the risk of systemic thromboembolism was useful to predict the onset of CHF, but not all‐cause death, in patients with NVAF.
Acute Chemical Incidents With Injured First Responders, 2002-2012
Authors: Melnikova Natalia , Wu Jennifer , Yang Alice , Orr Maureen
Published: August 2017

Introduction

First responders, including firefighters, police officers, emergency medical services, and company emergency response team members, have dangerous jobs that can bring them in contact with hazardous chemicals among other dangers. Limited information is available on responder injuries that occur during hazardous chemical incidents.

Methods

We analyzed 2002-2012 data on acute chemical incidents with injured responders from 2 Agency for Toxic Substances and Disease Registry chemical incident surveillance programs. To learn more about such injuries, we performed descriptive analysis and looked for trends.

Results

The percentage of responders among all injured people in chemical incidents has not changed over the years. Firefighters were the most frequently injured group of responders, followed by police officers. Respiratory system problems were the most often reported injury, and the respiratory irritants, ammonia, methamphetamine-related chemicals, and carbon monoxide were the chemicals more often associated with injuries. Most of the incidents with responder injuries were caused by human error or equipment failure. Firefighters wore personal protective equipment (PPE) most frequently and police officers did so rarely. Police officers’ injuries were mostly associated with exposure to ammonia and methamphetamine-related chemicals. Most responders did not receive basic awareness-level hazardous material training.

Conclusion

All responders should have at least basic awareness-level hazardous material training to recognize and avoid exposure. Research on improving firefighter PPE should continue. (Disaster Med Public Health Preparedness. 2018;12:211–221)
Diagnostic Imaging in Disasters: A Bibliometric Analysis
Authors: Gong Bo , Mohammed Mohammed F. , Nicolaou Savvas , Nasrullah Muazzam , Forster Bruce B. , Khosa Faisal
Published: August 2017

Objective

To investigate the role of diagnostic imaging in the clinical diagnosis, treatment, and follow-up management of patients in response to disasters.

Methods

A MEDLINE (OVID) search of original research articles identified 177 articles on this topic published since 2000. A bibliometric analysis was conducted on the top 100 articles ranked by average yearly citation.

Results

The most frequently studied disaster categories were disease outbreak (55 articles), armed conflict (23 articles), terrorist incident (10 articles), and earthquake (7 articles). The most studied disasters were the H1N1 influenza outbreak in 2009 (28 articles), Severe Acute Respiratory Syndrome outbreak in 2003 (24 articles), War in Afghanistan, 2001-2014 (8 articles), Iraq War, 2003-2011 (6 articles), and the Sichuan earthquake (China) in 2008 (6 articles). Among the first authors, 59 were primarily affiliated with Radiology. The United States of America produced the most articles (25 articles), followed by the People’s Republic of China (24 articles). Eighty-one studies were retrospective, with 19 studies being prospective. Computed tomography was the most investigated modality (52.8%), followed by conventional radiography (33.3%) and ultrasound (9.7%).

Conclusions

Our study identifies intellectual milestones in the utility of diagnostic imaging in response to various disasters, and could help guide future research in developing disaster management plans. (Disaster Med Public Health Preparedness. 2018;12:265–277)
The Importance of Self-Efficacy in Parental Emergency Preparedness: A Moderated Mediation Model
Authors: Ryan Meagan T. , Rohrbeck Cynthia A. , Wirtz Philip W.
Published: August 2017

Objective

Disasters occur without warning and can have devastating consequences. Emergency preparedness can reduce negative effects. It is especially important that parents prepare, as children are particularly vulnerable after disasters. This study tested 2 hypotheses: (1) adults with more children are likely to be better prepared than those with fewer or no children because greater caretaking is linked to greater perceived threat of disaster leading to greater preparedness and (2) the strength of this mediational link varies as a function of parental self-efficacy.

Methods

Data from an online survey about human-made disasters (terrorism) with a community convenience sample were used to test the hypothesis that perceived threat mediates the relationship between parental status (number of children cared for) and preparedness behaviors, moderated by level of self-efficacy for emergency preparedness.

Results

A bootstrapping analysis with relevant covariates supported the hypothesized mediating effect of threat on the relationship between parental status and preparedness. This relationship was strengthened at higher levels of parental preparedness self-efficacy.

Conclusions

The results of this study are particularly relevant for preparedness interventions. Because threat leads to preparedness, particularly for parents with high self-efficacy, it is important to focus attention on factors that can improve parents’ sense of self-efficacy. (Disaster Med Public Health Preparedness. 2018; 12: 345–351)
Litterfall mass and nutrient fluxes over an altitudinal gradient in the coastal Atlantic Forest, Brazil
Authors: de Sousa-Neto Eráclito Rodrigues , Lins Sílvia Rafaela Machado , Martins Susian Christian , Piccolo Marisa de Cássia , Ferreira Maurício Lamano , de Camargo Plínio Barbosa , Carmo Janaina Braga do , Mazzi Edmar Antonio , Houlton Benjamin Z. , Martinelli Luiz Antonio
Published: August 2017

Litterfall is one of the most important pathways through which nutrients are recycled in the terrestrial biosphere. In tropical soils, which are generally low in essential nutrients such as phosphorus and cations, the flux of nutrients through litterfall is particularly important to sustaining CO2-uptake capacity; however, questions remain over the role of altitude in altering litter nutrient cycling rates among tropical forest ecosystems. Here we examine litterfall, carbon (C), nitrogen (N) and phosphorus (P) fluxes through litterfall over an altitudinal gradient in the coastal Atlantic Forest located on the northern coast of the State of São Paulo, Brazil. Litterfall was collected twice a month for 1 y (April 2007–March 2008) using 30 litter traps placed in four different forest types arrayed by altitude – coastal forest (sea level), lowland forest (50–200 m asl), submontane forest (300–500 m asl) and montane forest (1000 m asl). Litterfall mass-fluxes decreased with increasing altitude, from ~9 Mg ha−1 in lowland forests to 7 Mg ha−1 in higher-altitude ecosystems. Contribution of reproductive organs to litterfall was significantly greater in lower than in higher altitudes. Litterfall N and P fluxes were higher in the lowland forest vs. other forest types, pointing to strong altitudinal controls over nutrient cycling. Furthermore, nitrogen-use efficiency (NUE) was lower and litter δ15N was higher in the lowland site providing additional evidence for lack of N constraints to productivity in lowland of the south-eastern Atlantic Forest.
Association of Sleep Quality on Memory-Related Executive Functions in Middle Age
Authors: Rana Brinda K. , Panizzon Matthew S. , Franz Carol E. , Spoon Kelly M. , Jacobson Kristen C. , Xian Hong , Ancoli-Israel Sonia , Lyons Michael , Kremen William S.
Published: August 2017

Objectives:Sleep quality affects memory and executive function in older adults, but little is known about its effects in midlife. If it affects cognition in midlife, it may be a modifiable factor for later-life functioning.Methods:We examined the association between sleep quality and cognition in 1220 middle-aged male twins (age 51–60 years) from the Vietnam Era Twin Study of Aging. We interviewed participants with the Pittsburgh Sleep Quality Index and tested them for episodic memory as well as executive functions of inhibitory and interference control, updating in working memory, and set shifting. Interference control was assessed during episodic memory, inhibitory control during working memory, and non-memory conditions and set shifting during working memory and non-memory conditions.Results:After adjusting for covariates and correcting for multiple comparisons, sleep quality was positively associated with updating in working memory, set shifting in the context of working memory, and better visual-spatial (but not verbal) episodic memory, and at trend level, with interference control in the context of episodic memory.Conclusions:Sleep quality was associated with visual-spatial recall and possible resistance to proactive/retroactive interference. It was also associated with updating in working memory and with set shifting, but only when working memory demands were relatively high. Thus, effects of sleep quality on midlife cognition appear to be at the intersection of executive function and memory processes. Subtle deficits in these age-susceptible cognitive functions may indicate increased risk for decline in cognitive abilities later in life that might be reduced by improved midlife sleep quality. (JINS, 2018,24, 67–76)
Draining the Swamp: Understanding the Crisis in Mainstream Politics as a Crisis of the State
Authors: Innes Abby
Published: August 2017

This paper examines Poland, Hungary, the UK and the US the most surprising cases of populist reaction. It argues that the social polarization caused by the failures of hyper-liberal reforms to the state, and the association of Social Democratic parties with those reforms, has provoked alienation from liberal democratic politics.
Red Scares and Orange Mobilizations: A Critical Anthropological Perspective on the Russian Hacking Scandal
Authors: Hemment Julie
Published: August 2017

This essay considers the Russian hacking controversy, which has been a prominent theme of the US Presidential election season. Tracking the context and contours of the scandal, I consider some of the anxieties, phobias and cultural logics that animate it (both in Russia and the US) and reflect on the dynamics that drive it.
TRPA1 channel mediates organophosphate-induced delayed neuropathy
Authors: Ding Qiang , Fang Sui , Chen Xueqin , Wang Youxin , Li Jian , Tian Fuyun , Xu Xiang , Attali Bernard , Xie Xin , Gao Zhaobing
Published: August 2017

The organophosphate-induced delayed neuropathy (OPIDN), often leads to paresthesias, ataxia and paralysis, occurs in the late-stage of acute poisoning or after repeated exposures to organophosphate (OP) insecticides or nerve agents, and may contribute to the Gulf War Syndrome. The acute phase of OP poisoning is often attributed to acetylcholinesterase inhibition. However, the underlying mechanism for the delayed neuropathy remains unknown and no treatment is available. Here we demonstrate that TRPA1 channel (Transient receptor potential cation channel, member A1) mediates OPIDN. A variety of OPs, exemplified by malathion, activates TRPA1 but not other neuronal TRP channels. Malathion increases the intracellular calcium levels and upregulates the excitability of mouse dorsal root ganglion neurons in vitro. Mice with repeated exposures to malathion also develop local tissue nerve injuries and pain-related behaviors, which resembles OPIDN. Both the neuropathological changes and the nocifensive behaviors can be attenuated by treatment of TRPA1 antagonist HC030031 or abolished by knockout of Trpa1 gene. In the classic hens OPIDN model, malathion causes nerve injuries and ataxia to a similar level as the positive inducer tri-ortho-cresyl phosphate (TOCP), which also activates TRPA1 channel. Treatment with HC030031 reduces the damages caused by malathion or tri-ortho-cresyl phosphate. Duloxetine and Ketotifen, two commercially available drugs exhibiting TRPA1 inhibitory activity, show neuroprotective effects against OPIDN and might be used in emergency situations. The current study suggests TRPA1 is the major mediator of OPIDN and targeting TRPA1 is an effective way for the treatment of OPIDN.
Utrophin Compensates dystrophin Loss during Mouse Spermatogenesis
Authors: Chen Hung-Chih , Chin Yu-Feng , Lundy David J. , Liang Chung-Tiang , Chi Ya-Hui , Kuo Paolin , Hsieh Patrick C. H.
Published: August 2017

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder resulting from mutations in the dystrophin gene. The mdx/utrn−/− mouse, lacking in both dystrophin and its autosomal homologue utrophin, is commonly used to model the clinical symptoms of DMD. Interestingly, these mice are infertile but the mechanisms underlying this phenomenon remain unclear. Using dystrophin deficient mdx mouse and utrophin haplodeficient mdx/utrn+/− mouse models, we demonstrate the contribution of Dp427 (full-length dystrophin) and utrophin to testis and epididymis development, as well as spermatogenesis. We show that Dp427 deficiency disturbed the balance between proliferation and apoptosis of germ cells during spermatogenesis, which was further disrupted with utrophin haplodeficiency, deciphering a compensatory role of utrophin for dystrophin in the male reproductive system. In the spermatozoa, we have found a compensatory response of utrophin to dystrophin deficiency - namely the upregulation and relocation of utrophin to the flagellar midpiece. This study demonstrates the contribution of Dp427 and utrophin in male fertility, suggesting a potential pathology in DMD patients.
CD146 is required for VEGF-C-induced lymphatic sprouting during lymphangiogenesis
Authors: Yan Huiwen , Zhang Chunxia , Wang Zhaoqing , Tu Tao , Duan Hongxia , Luo Yongting , Feng Jing , Liu Feng , Yan Xiyun
Published: August 2017

VEGF-C is essential for lymphangiogenesis during development and tumor progression. VEGFR-3 is the well-known cognate receptor of VEGF-C to regulate lymphatic migration and proliferation, but the receptor of VEGF-C in regulating lymphatic sprouting, the initiating step of lymphangiogenesis, still remains elusive. Here we use both in vitro and in vivo methods to demonstrate CD146 as a receptor of VEGF-C to regulate lymphangiogenesis, especially at the sprouting step. Mechanistically, CD146 selectively activates the downstream p38 kinase, upon VEGF-C stimulation, to regulate lymphatic sprouting. Moreover, CD146 can also activate ERK to mediate VEGF-C regulation of the subsequent proliferation and migration of lymphatic endothelial cells. In zebrafish embryos, knockdown or dysfunction of CD146 results in similar developmental defects in lymphatic sprouting, capillary network, parachordal lymphangioblast (PL), and thoracic duct (TD) similar to down-regulation of VEGF-C. Altogether, our data reveals a critical role of CD146 to mediate VEGF-C signaling pathway in lymphangiogenesis.
Mixture of easy trials enables transient and sustained perceptual improvements through priming and perceptual learning
Authors: Lin Zhicheng , Dosher Barbara Anne , Lu Zhong-Lin
Published: August 2017

The sense of vision allows us to discriminate fine details across a wide range of tasks. How to improve this perceptual skill, particularly within a short training session, is of substantial interest. Emerging evidence suggests that mixing easy trials can quickly improve performance in hard trials, but it is equivocal whether the improvement is short-lived or long-lasting, and additionally what accounts for this improvement. Here, by tracking objective performance (accuracy) and subjective experience (ratings of target visibility and choice confidence) over time and in a large sample of participants, we demonstrate the coexistence of transient and sustained effects of mixing easy trials, which differ markedly in their timescales, in their effects on subjective awareness, and in individual differences. In particular, whereas the transient effect was found to be ubiquitous and manifested similarly across objective and subjective measures, the sustained effect was limited to a subset of participants with weak convergence from objective and subjective measures. These results indicate that mixture of easy trials enables two distinct, co-existing forms of rapid perceptual improvements in hard trials, as mediated by robust priming and fragile learning. Placing constraints on theory of brain plasticity, this finding may also have implications for alleviating visual deficits.
Altered leaf functional traits by nitrogen addition in a nutrient-poor pine plantation: A consequence of decreased phosphorus availability
Authors: Zheng Lin-Lin , Zhao Qiong , Yu Zhan-Yuan , Zhao Shan-Yu , Zeng De-Hui
Published: August 2017

This study aimed to determine how specific leaf area (SLA) and leaf dry matter content (LDMC) respond to N addition and understory vegetation removal in a 13-year-old Mongolian pine (Pinus sylvestrisvar.mongolica) plantation. Traits (SLA, LDMC, individual needle dry weight, N and P concentrations) of different-aged needles and their crown-average values were measured, and their relationships with soil N and P availability were examined. N addition and understory removal reduced soil Olsen-P by 15–91%. At the crown level, N addition significantly reduced foliar P concentration (by 19%) and SLA (by 8%), and elevated N concentration (by 31%), LDMC (by 10%) and individual leaf dry weight (by 14%); understory removal did not have a significant effect on all leaf traits. At the needle age level, traits of the previous year’s needles responded more strongly to N addition and understory removal than the traits of current-year needles, particularly SLA and N concentration. SLA and LDMC correlated more closely with soil Olsen-P than with soil inorganic N, and LDMC correlated more closely with soil Olsen-P than SLA did. These results indicate that aggravated P limitation resulting from N addition and understory removal could constrain Mongolian pine growth through their effects on the leaf traits.
Human Brainstem Exhibits higher Sensitivity and Specificity than Auditory-Related Cortex to Short-Term Phonetic Discrimination Learning
Authors: Elmer Stefan , Hausheer Marcela , Albrecht Joëlle , Kühnis Jürg
Published: August 2017

Phonetic discrimination learning is an active perceptual process that operates under the influence of cognitive control mechanisms by increasing the sensitivity of the auditory system to the trained stimulus attributes. It is assumed that the auditory cortex and the brainstem interact in order to refine how sounds are transcribed into neural codes. Here, we evaluated whether these two computational entities are prone to short-term functional changes, whether there is a chronological difference in malleability, and whether short-term training suffices to alter reciprocal interactions. We performed repeated cortical (i.e., mismatch negativity responses, MMN) and subcortical (i.e., frequency-following response, FFR) EEG measurements in two groups of participants who underwent one hour of phonetic discrimination training or were passively exposed to the same stimulus material. The training group showed a distinctive brainstem energy reduction in the trained frequency-range (i.e., first formant), whereas the passive group did not show any response modulation. Notably, brainstem signal change correlated with the behavioral improvement during training, this result indicating a close relationship between behavior and underlying brainstem physiology. Since we did not reveal group differences in MMN responses, results point to specific short-term brainstem changes that precede functional alterations in the auditory cortex.
Orientational Mapping Augmented Sub-Wavelength Hyper-Spectral Imaging of Silk
Authors: Ryu Meguya , Balčytis Armandas , Wang Xuewen , Vongsvivut Jitraporn , Hikima Yuta , Li Jingliang , Tobin Mark J. , Juodkazis Saulius , Morikawa Junko
Published: August 2017

Molecular alignment underpins optical, mechanical, and thermal properties of materials, however, its direct measurement from volumes with micrometer dimensions is not accessible, especially, for structurally complex bio-materials. How the molecular alignment is linked to extraordinary properties of silk and its amorphous-crystalline composition has to be accessed by a direct measurement from a single silk fiber. Here, we show orientation mapping of the internal silk fiber structure via polarisation-dependent IR absorbance at high spatial resolution of 4.2 μm and 1.9 μm in a hyper-spectral IR imaging by attenuated total reflection using synchrotron radiation in the spectral fingerprint region around 6 μm wavelength. Free-standing longitudinal micro-slices of silk fibers, thinner than the fiber cross section, were prepared by microtome for the four polarization method to directly measure the orientational sensitivity of absorbance in the molecular fingerprint spectral window of the amide bands of β-sheet polypeptides of silk. Microtomed lateral slices of silk fibers, which may avoid possible artefacts that affect spectroscopic measurements with fibers of an elliptical cross sections were used in the study. Amorphisation of silk by ultra-short laser single-pulse exposure is demonstrated.
Humid heat waves at different warming levels
Authors: Russo Simone , Sillmann Jana , Sterl Andreas
Published: August 2017

The co-occurrence of consecutive hot and humid days during a heat wave can strongly affect human health. Here, we quantify humid heat wave hazard in the recent past and at different levels of global warming. We find that the magnitude and apparent temperature peak of heat waves, such as the ones observed in Chicago in 1995 and China in 2003, have been strongly amplified by humidity. Climate model projections suggest that the percentage of area where heat wave magnitude and peak are amplified by humidity increases with increasing warming levels. Considering the effect of humidity at 1.5° and 2° global warming, highly populated regions, such as the Eastern US and China, could experience heat waves with magnitude greater than the one in Russia in 2010 (the most severe of the present era). The apparent temperature peak during such humid-heat waves can be greater than 55 °C. According to the US Weather Service, at this temperature humans are very likely to suffer from heat strokes. Humid-heat waves with these conditions were never exceeded in the present climate, but are expected to occur every other year at 4° global warming. This calls for respective adaptation measures in some key regions of the world along with international climate change mitigation efforts.
A high-throughput chemical screen identifies novel inhibitors and enhancers of anti-inflammatory functions of the glucocorticoid receptor
Authors: Jiang Xiaofeng , Dahlin Amber , Weiss Scott T. , Tantisira Kelan , Lu Quan
Published: August 2017

Glucocorticoids (GCs)—ligands of the glucocorticoid receptor (GR)—are widely used to treat inflammatory diseases, but suffer from significant side effects and poor responsiveness in certain patient populations. Identification of chemical GR modulators may provide insights into the regulatory mechanisms of anti-inflammatory functions of GR and help improve GC-based therapy. Here we report the development and application of a high-throughput screening to identify compounds that either enhance or suppress the anti-inflammatory effect of GR function. Using a cell-based GR activity assay that measures Dexamethasone (Dex)-mediated NF-κB repression, we have screened ~8,000 compounds and identified several compounds that suppressed GR activity, including multiple GSK3β inhibitors and anti-cancer agent camptothecin. Notably, we also identified two kinase IKK2 inhibitors, including TPCA-1, as GR enhancers that improve the anti-inflammatory effect of GR. In particular, TPCA-1 augmented the activity of Dex in NF-κB repression by attenuating GR down-regulation. Consistent with the observation, siRNA-mediated IKK2 knockdown decreased GR down-regulation and increased GR expression. Together, our results identified chemical compounds as novel modulators of GR and revealed an unexpected role for IKK2 in GR down-regulation. Furthermore, we have established a high-throughput screening platform for discovering GR-modulating compounds that may be repurposed to improve current GC-based therapies.
Complete Acid Ceramidase ablation prevents cancer-initiating cell formation in melanoma cells
Authors: Lai Michele , Realini Natalia , La Ferla Marco , Passalacqua Ilaria , Matteoli Giulia , Ganesan Anand , Pistello Mauro , Mazzanti Chiara Maria , Piomelli Daniele
Published: August 2017

Acid ceramidase (AC) is a lysosomal cysteine hydrolase that catalyzes the conversion of ceramide into fatty acid and sphingosine. This reaction lowers intracellular ceramide levels and concomitantly generates sphingosine used for sphingosine-1-phosphate (S1P) production. Since increases in ceramide and consequent decreases of S1P reduce proliferation of various cancers, AC might offer a new target for anti-tumor therapy. Here we used CrispR-Cas9-mediated gene editing to delete the gene encoding for AC, ASAH1, in human A375 melanoma cells. ASAH1-null clones show significantly greater accumulation of long-chain saturated ceramides that are substrate for AC. As seen with administration of exogenous ceramide, AC ablation blocks cell cycle progression and accelerates senescence. Importantly, ASAH1-null cells also lose the ability to form cancer-initiating cells and to undergo self-renewal, which is suggestive of a key role for AC in maintaining malignancy and self-renewal of invasive melanoma cells. The results suggest that AC inhibitors might find therapeutic use as adjuvant therapy for advanced melanoma.
Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming
Authors: Bernstock Joshua D. , Ye Daniel , Gessler Florian A. , Lee Yang-ja , Peruzzotti-Jametti Luca , Baumgarten Peter , Johnson Kory R. , Maric Dragan , Yang Wei , Kögel Donat , Pluchino Stefano , Hallenbeck John M.
Published: August 2017

Protein SUMOylation is a dynamic post-translational modification shown to be involved in a diverse set of physiologic processes throughout the cell. SUMOylation has also been shown to play a role in the pathobiology of myriad cancers, one of which is glioblastoma multiforme (GBM). As such, the clinical significance and therapeutic utility offered via the selective control of global SUMOylation is readily apparent. There are, however, relatively few known/effective inhibitors of global SUMO-conjugation. Herein we describe the identification of topotecan as a novel inhibitor of global SUMOylation. We also provide evidence that inhibition of SUMOylation by topotecan is associated with reduced levels of CDK6 and HIF-1α, as well as pronounced changes in cell cycle progression and cellular metabolism, thereby highlighting its putative role as an adjuvant therapy in defined GBM patient populations.
Deformation behavior of Re alloyed Mo thin films on flexible substrates: In situ fragmentation analysis supported by first-principles calculations
Authors: Jörg Tanja , Music Denis , Hauser Filipe , Cordill Megan J. , Franz Robert , Köstenbauer Harald , Winkler Jörg , Schneider Jochen M. , Mitterer Christian
Published: August 2017

A major obstacle in the utilization of Mo thin films in flexible electronics is their brittle fracture behavior. Within this study, alloying with Re is explored as a potential strategy to improve the resistance to fracture. The sputter-deposited Mo1−xRexfilms (with 0 ≤ x ≤ 0.31) were characterized in terms of structural and mechanical properties, residual stresses as well as electrical resistivity. Their deformation behavior was assessed by straining 50 nm thin films on polyimide substrates in uniaxial tension, while monitoring crack initiation and propagationin situby optical microscopy and electrical resistance measurements. A significant toughness enhancement occurs with increasing Re content for all body-centered cubic solid solution films (x ≤ 0.23). However, at higher Re concentrations (x > 0.23) the positive effect of Re is inhibited due to the formation of dual-phase films with the additional close packed A15 Mo3Re phase. The mechanisms responsible for the observed toughness behavior are discussed based on experimental observations and electronic structure calculations. Re gives rise to both increased plasticity and bond strengthening in these Mo-Re solid solutions.
Intraspecies and interspecies transmission of mink H9N2 influenza virus
Authors: Yong-feng Zhao , Fei-fei Diao , Jia-yu Yu , Feng-xia Zhang , Chang-qing Jiang , Jian-li Wang , Shou-yu Guo , Kai Cui , Chuan-yi Liu , Xue-hua Wei , Jiang Shi-jin , Zhi-jing Xie
Published: August 2017

H9N2 influenza A virus (IAV) causes low pathogenic respiratory disease and infects a wide range of hosts. In this study, six IAVs were isolated from mink and identified as H9N2 IAV. Sequence analysis revealed that the six isolates continued to evolve, and their PB2 genes shared high nucleotide sequence identity with H7N9 IAV. The six isolates contained an amino acid motif PSRSSR↓GL at the hemagglutinin cleavage site, which is a characteristic of low pathogenic influenza viruses. A serosurvey demonstrated that H9N2 IAV had spread widely in mink and was prevalent in foxes and raccoon dogs. Transmission experiments showed that close contact between H9N2-infected mink and naive mink, foxes and raccoon dogs resulted in spread of the virus to the contact animals. Furthermore, H9N2 challenge experiments in foxes and raccoon dogs showed that H9N2 IAV could infect these hosts. Virological and epidemiological surveillance of H9N2 IAV should be strengthened for the fur animal industry.
Hypoxia induced mitogenic factor (HIMF) triggers angiogenesis by increasing interleukin-18 production in myoblasts
Authors: Su Chen-Ming , Wang I-Ching , Liu Shan-Chi , Sun Yi , Jin Lulu , Wang Shih-Wei , Lee Hsiang-Ping , Tseng Wen-Pei , Tang Chih-Hsin
Published: August 2017

Inflammatory myopathy is a rare autoimmune muscle disorder. Treatment typically focuses on skeletal muscle weakness or inflammation within muscle, as well as complications of respiratory failure secondary to respiratory muscle weakness. Impaired respiratory muscle function contributes to increased dyspnea and reduced exercise capacity in pulmonary hypertension (PH), a debilitating condition that has few treatment options. The initiation and progression of PH is associated with inflammation and inflammatory cell recruitment and it is established that hypoxia-induced mitogenic factor (HIMF, also known as resistin-like molecule α), activates macrophages in PH. However, the relationship between HIMF and inflammatory myoblasts remains unclear. This study investigated the signaling pathway involved in interleukin-18 (IL-18) expression and its relationship with HIMF in cultured myoblasts. We found that HIMF increased IL-18 production in myoblasts and that secreted IL-18 promoted tube formation of the endothelial progenitor cells. We used the mouse xenograft model and the chick chorioallantoic membrane assay to further explore the role of HIMF in inflammatory myoblasts and angiogenesis in vivo. Thus, our study focused on the mechanism by which HIMF mediates IL-18 expression in myoblasts through angiogenesis in vitro and in vivo. Our findings provide an insight into HIMF functioning in inflammatory myoblasts.
Synthesis and fluorescence spectroscopy of tris(pyrenyl)pnictogen compounds
Authors: Behm Kira , Essner Jeremy B. , Barnes Charles L. , Baker Gary A. , Walensky Justin R.
Published: August 2017

A homologous series of tris(pyrenyl)pnictogen compounds has been prepared and studied, revealing the dramatic impact of pnictogen choice on fluorescence quantum yield and photophysical properties.
Novel mononuclear Ln complexes with pyrazine-2-carboxylate and acetylacetonate co-ligands: remarkable single molecule magnet behavior of a Yb derivative
Authors: Gavrikov Andrey V. , Efimov Nikolay N. , Dobrokhotova Zhanna V. , Ilyukhin Andrey B. , Vasilyev Pavel N. , Novotortsev Vladimir M.
Published: August 2017

A series of novel mononuclear complexes were prepared, and the Yb derivative exhibits the highest Δeff/kB value known for ytterbium complexes.
Antioxidant and anti-inflammatory effects of cauliflower leaf powder-enriched diet against LPS induced toxicity in rabbits
Authors: Larocca Marilena , Perna Anna Maria , Simonetti Amalia , Gambacorta Emilio , Iannuzzi Alessandra , Perucatti Angela , Rossano Rocco
Published: August 2017

Brassicaphytochemicals exert a broad spectrum of health-promoting activities.
Ezetimibe alleviates non-alcoholic fatty liver disease through the miR-16 inhibiting mTOR/p70S6K1 pathway
Authors: Wang Xiang , Meng Yunbing , Zhang Junrong
Published: August 2017

Emerging studies have indicated the role of ezetimibe, miR-16 and mTOR signaling in non-alcoholic fatty liver disease (NAFLD).
Sintered metal fibers@carbon molecular sieve membrane (SMFs@CMSM) composites for the adsorptive removal of low concentration isopropanol
Authors: Shao Yan , Chen Huanhao , Li Yibiao , Xie Shan , Li Bin
Published: August 2017

Structured fixed-bed adsorber based on SMF@CMSM adsorbents show enhanced mass transfer and 3 bed utilization efficiency.
Enhanced charge collection and stability in planar perovskite solar cells based on a cobalt(iii)-complex additive
Authors: Ma Yunping , Fan Jiandong , Zhang Cuiling , Li Hongliang , Li Wenzhe , Mai Yaohua
Published: August 2017

Chemical doping has emerged as a favourable method for tuning the electrical properties of the hole-transport layer (HTL) in perovskite solar cells.
Facile synthesis of Cu/Ni alloy nanospheres with tunable size and elemental ratio
Authors: Liu Jinglei , Zheng Yiqun , Hou Shifeng
Published: August 2017

We report a facile synthesis of copper/nickel (Cu/Ni) alloy nanospheres in high purity and with tunable, well-controlled sizes and elemental ratios.
Targeted isolation of sulfur-containing metabolites from Lsr2-deletion mutant strain of Streptomyces roseosporus
Authors: Deng Lina , Wang Rui , Wang Guowei , Liu Mingxu , Liao Guojian , Liao Zhihua , Chen Min
Published: August 2017

UPLC-QTOF-MS/MS targeted isolation of novel sulfur-containing metabolites, pyrismycins A–F, from a Lsr2-deletion mutant strain of Streptomyces roseosporus.
Photo-sensitive benzoxazine II: chalcone-containing benzoxazine and its photo and thermal-cured thermoset
Authors: Lin Ching Hsuan , Chien Chun Kai , Chen Chien Han , Juang Tzong Yuan
Published: August 2017

Chalcone-containing benzoxazine (BHP-a) was synthesized. Two procedures were applied to cure BHP-a, thermal curing of chalcone and oxazine moieties. Another one was photo curing the chalcone moiety, followed by thermal curing of the oxazine moiety.
Steric effect on Li+ coordination and transport properties in polyoxetane-based polymer electrolytes bearing nitrile groups
Authors: Sai Ryansu , Ueno Kazuhide , Fujii Kenta , Nakano Yohei , Tsutsumi Hiromori
Published: August 2017

The steric hindrance of the ethyl groups in poly(3-(2-cyanoethoxymethyl)-3-ethyloxetane) resulted in more-pronounced Li+ coordination with the nitrile side chains.
Executive Functions Impact the Relation Between Respiratory Sinus Arrhythmia and Frequency of Stuttering in Young Children Who Do and Do Not Stutter
Authors: Jones Robin M. , Walden Tedra A. , Conture Edward G. , Erdemir Aysu , Lambert Warren E. , Porges Stephen W.
Published: August 2017

Purpose

This study sought to determine whether respiratory sinus arrhythmia (RSA) and executive functions are associated with stuttered speech disfluencies of young children who do (CWS) and do not stutter (CWNS).

Method

Thirty-six young CWS and 36 CWNS were exposed to neutral, negative, and positive emotion-inducing video clips, followed by their participation in speaking tasks. During the neutral video, we measured baseline RSA, a physiological index of emotion regulation, and during video viewing and speaking, we measured RSA change from baseline, a physiological index of regulatory responses during challenge. Participants' caregivers completed the Children's Behavior Questionnaire from which a composite score of the inhibitory control and attentional focusing subscales served to index executive functioning.

Results

For both CWS and CWNS, greater decrease of RSA during both video viewing and speaking was associated with more stuttering. During speaking, CWS with lower executive functioning exhibited a negative association between RSA change and stuttering; conversely, CWNS with higher executive functioning exhibited a negative association between RSA change and stuttering.

Conclusion

Findings suggest that decreased RSA during video viewing and speaking is associated with increased stuttering and young CWS differ from CWNS in terms of how their executive functions moderate the relation between RSA change and stuttered disfluencies.
Understanding Word Reading Difficulties in Children With SLI
Authors: Adlof Suzanne M.
Published: August 2017

Children with specific language impairment (SLI) often show considerable reading difficulties. Research has revealed two primary reading profiles among children with SLI: (a) one of poor word reading and decoding skills and associated reading comprehension difficulties, and (b) one involving relatively strong word reading skills but poor comprehension. This article reviews studies characterizing these two subtypes of SLI, discusses their current clinical implications, and suggests important directions for future study.
Small Group Reading Instruction: Activities for Teaching Phonemic Awareness, the Alphabetic Principle, and Phonics in a Tier 2 Setting
Authors: Henbest Victoria S.
Published: August 2017

Explicit and systematic instruction in phonemic awareness, the alphabetic principle, and phonics are critical for children who are struggling to read words. Further, it is the responsibility of the speech-language pathologist (SLP) to provide intervention for students that present with written language difficulties including those who have not yet been identified as having a disability. This paper serves as a guide for SLPs who aim to improve the word reading skills of young elementary-age students in a small group setting, characteristic of Tier 2 in a Response to Intervention (RTI) framework. First, phonemic awareness, the alphabetic principle, and phonics are defined and their critical roles for success with early word reading are discussed. Next, examples of activities addressing each of these skills are provided including the rationale for each activity, required materials, and additional considerations and/or modifications for students with varying skill levels. The paper concludes with further important considerations when addressing the word reading skills of young struggling readers.
Asymptotic analysis of two‐layer D‐BLAST with group‐zero forcing detection in general channels
Authors: Sundaramurthi Rajarajan , Chaturvedi Sanjay Kumar
Published: July 2017

In this study, the authors perform the asymptotic analysis of two‐layer D‐BLAST transmission scheme with group detection receiver under broad class of fading channels. The asymptotic analysis includes both diversity‐multiplexing trade‐off (DMT) and throughput‐reliability trade‐off (TRT) analyses. The D‐BLAST considered here is a multi‐layered space–time transmission scheme, wherein each diagonal of code‐word forms a group. On the other hand, group detection considered detects symbols by nulling out interference from other groups and performs maximum‐likelihood decoding on the chosen group. The reason for choosing this scheme is that the first inflexion of DMT of this system ceases at multiplexing gain ≪1, i.e. second inflexion began at multiplexing gain <1 under Gaussian fading scenario. The results of DMT indicate that the system behaves differently in different fading channel constraints when multiplexing gain ≪1. The results of the TRT analysis show that the system performs different in different fading channels in the zeroth operating region.
Smart load management of distribution‐class toroidal transformers using a dynamic thermal model
Authors: Lu Haowei , Borbuev Akim , Jazebi Saeed , Hong Tianqi , de León Francisco
Published: July 2017

Thermal behaviour is a prime factor in the accurate performance assessment of power transformers as well as in the prediction of their life expectancy. This study presents a computer modelling tool based on an electro‐thermal equivalent circuit of transformers that is able to predict the hot‐spot temperature and average surface temperatures for all internal layers of distribution‐class toroidal transformers. Temperature is the limiting factor that prevents running transformers for hours or days in overload conditions. The modelling tool presented in this study is capable to identify the safe maximum overload current and duration that a transformer can handle without introducing damage or loss of life. The model is helpful to predict the short‐term (few hours) and long‐term (few days) overload capabilities of transformers. The electro‐thermal model can also be used as a tool to optimise the design and evaluate the performance of transformers. This study is specifically focused on the implementation of the proposed method on dry‐type distribution‐grade toroidal transformers. The model is built using circuit components (lumped R and C) obtained from the thermal–electrical analogy. The model is validated with numerous finite‐element method simulations and laboratory tests with transformers of various power ratings.