bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonal variation of secondary metabolites in nine different bryophytes
Authors: Peters Kristian , Gorzolka Karin , Bruelheide Helge , Neumann Steffen
Published: August 2018

Bryophytes occur in almost all land ecosystems and contribute to global biogeochemical cycles, ecosystem functioning, and influence vegetation dynamics. As growth and biochemistry of bryophytes are strongly dependent on the season, we analyzed metabolic variation across seasons with regard to ecological characteristics and phylogeny. Using bioinformatics methods, we present an integrative and reproducible approach to connect ecology with biochemistry. Nine different bryophyte species were collected in three composite samples in four seasons. Untargeted liquid chromatography coupled with mass spectrometry (LC/MS) was performed to obtain metabolite profiles. Redundancy analysis, Pearson's correlation, Shannon diversity, and hierarchical clustering were used to determine relationships among species, seasons, ecological characteristics, and hierarchical clustering. Metabolite profiles of Marchantia polymorpha and Fissidens taxifolius which are species with ruderal life strategy (R‐selected) showed low seasonal variability, while the profiles of the pleurocarpous mosses and Grimmia pulvinata which have characteristics of a competitive strategy (C‐selected) were more variable. Polytrichum strictum and Plagiomnium undulatum had intermediary life strategies. Our study revealed strong species‐specific differences in metabolite profiles between the seasons. Life strategies, growth forms, and indicator values for light and soil were among the most important ecological predictors. We demonstrate that untargeted Eco‐Metabolomics provide useful biochemical insight that improves our understanding of fundamental ecological strategies.
Detecting ecological regime shifts from transect data
Authors: Ward Delphi F. L. , Wotherspoon Simon , Melbourne‐Thomas Jessica , Haapkylä Jessica , Johnson Craig R.
Published: August 2018

Timely detection of ecological regime shifts is a key problem for ecosystem managers, because changed ecosystem dynamics and function will usually necessitate a change in management strategies. However, currently available methods for detecting regime shifts depend on having multiple long time series data from both before and after the regime shift. This data requirement is prohibitive for many ecosystems. Here, we present a new approach for detecting regime shifts from one‐dimensional spatial (transect) data from just a single time step either side of the transition. Characteristic length scale (CLS) estimation is a method of attractor reconstruction combined with nonlinear prediction that enables identification of the emergent scale at which deterministic behavior of the system is best observed. Importantly, previous studies show that a fundamental change in ecosystem dynamics, from one domain of attraction to another, is reflected in a change in the CLS, i.e., the approach enables distinguishing regime shifts from variability in dynamics around a single attractor. Until now the method required highly resolved two‐dimensional spatial data, but here we adapted the approach so that the CLS can be estimated from one‐dimensional transect data. We demonstrate its successful application to both model and real ecosystem data. In our model test cases, we detected change in the CLS in cases where the shape (topology) of the interaction network had changed, leading to a shift in community composition. In an examination of benthic transect data from four Indonesian coral reefs, changes in the CLS for two of the reefs indicate a regime shift. This new development in estimating CLSs makes it possible to detect regime shifts in systems where data are limited, removing ambiguity in the interpretation of community change.
Managing fishery development in sensitive ecosystems: identifying penguin habitat use to direct management in Antarctica
Authors: Trathan P. N. , Warwick‐Evans V. , Hinke J. T. , Young E. F. , Murphy E. J. , Carneiro A. P. B. , Dias M. P. , Kovacs K. M. , Lowther A. D. , Godø O. R. , Kokubun N. , Kim J. H. , Takahashi A. , Santos M.
Published: August 2018

In the Southern Ocean, the at‐sea distributions of most predators of Antarctic krill are poorly known, primarily because tracking studies have only been undertaken on a restricted set of species, and then only at a limited number of sites. For chinstrap penguins, one of the most abundant krill predators breeding across the Antarctic Peninsula, we show that habitat models developed utilizing the distance from the colony and the bearing to the shelf‐edge, adjusting for the at‐sea density of Pygoscelis penguins from other colonies, can be used to predict, with a high level of confidence, the at‐sea distribution of chinstrap penguins from untracked colonies during the breeding season. Comparison of predicted penguin distributions with outputs from a high‐resolution oceanographic model shows that chinstrap penguins prefer nearshore habitats, over shallow bathymetry, with slow‐flowing waters, but that they sometimes also travel to areas beyond the edge of the continental shelf where the faster‐flowing waters of the Coastal Current or the fronts of the Antarctic Circumpolar Current occur. In the slow‐moving shelf waters, large penguin colonies may lead to krill depletion during incubation and chick‐rearing periods when penguins are acting as central place foragers. The habitats used by chinstrap penguins are also locations preferentially used by the commercial krill fishery, one of the last under‐developed marine capture fisheries anywhere on the planet. As it develops, this fishery has the potential to compete with chinstrap penguins and other natural krill predators. Scaling our habitat models by chinstrap penguin population data demonstrates where overlap with the fishery is likely to be most important. Our results suggest that a better understanding of krill retention and krill depletion in areas used by natural predators and by the krill fishery are needed, and that risk management strategies for the fishery should include assessment of how krill movement can satisfy the demands of both natural predators and the fishery across a range of spatial and temporal scales. Such information will help regional management authorities better understand how plausible ecosystem‐based management frameworks could be developed to ensure sustainable co‐existence of the fishery and competing natural predators.
STEPWAT2: an individual‐based model for exploring the impact of climate and disturbance on dryland plant communities
Authors: Palmquist Kyle A. , Bradford John B. , Martyn Trace E. , Schlaepfer Daniel R. , Lauenroth William K.
Published: August 2018

The combination of climate change and altered disturbance regimes is directly and indirectly affecting plant communities by mediating competitive interactions, resulting in shifts in species composition and abundance. Dryland plant communities, defined by low soil water availability and highly variable climatic regimes, are particularly vulnerable to climatic changes that exceed their historical range of variability. Individual‐based simulation models can be important tools to quantify the impacts of climate change, altered disturbance regimes, and their interaction on demographic and community‐level responses because they represent competitive interactions between individuals and individual responses to fluctuating environmental conditions. Here, we introduce STEPWAT2, an individual plant‐based simulation model for exploring the joint influence of climate change and disturbance regimes on dryland ecohydrology and plant community composition. STEPWAT2 utilizes a process‐based soil water model (SOILWAT2) to simulate available soil water in multiple soil layers, which plant individuals compete for based on the temporal matching of water and active root distributions with depth. This representation of resource utilization makes STEPWAT2 particularly useful for understanding how changes in soil moisture and altered disturbance regimes will concurrently impact demographic and community‐level responses in drylands. Our goals are threefold: (1) to describe the core modules and functions within STEPWAT2 (model description), (2) to validate STEPWAT2 model output using field data from big sagebrush plant communities (model validation), and (3) to highlight the usefulness of STEPWAT2 as a modeling framework for examining the impacts of climate change and disturbance regimes on dryland plant communities under future conditions (model application). To address goals 2 and 3, we focus on 15 sites that span the spatial extent of big sagebrush plant communities in the western United States. For goal 3, we quantify how climate change, fire, and grazing can interact to influence plant functional type biomass and composition. We use big sagebrush‐dominated plant communities to demonstrate the functionality of STEPWAT2, as these communities are among the most widespread dryland ecosystems in North America.
Fish farm effluents are suitable growth media for Nannochloropsis gaditana, a polyunsaturated fatty acid producing microalga
Authors: Dourou Marianna , Tsolcha Olga N. , Tekerlekopoulou Athanasia G. , Bokas Dimitrios , Aggelis George
Published: August 2018

Fish farm effluents may be used as culture media for marine microalgae, the cell mass of which constitute an excellent fish feed rich in bioactive compounds. In the current investigation different fish farm effluents were tested as culture media for Nannochloropsis strains. Among them, Nannochloropsis gaditana grew well on the effluent released from the sedimentation tank (EST), which is the final step of the wastewater treatment. Mono‐algal but non‐aseptic cultures were conducted in two types of photo‐bioreactors, namely stirred tank reactor (STR) and open pond simulating reactor (OPSR) working under various photoperiods. N. gaditana grew well under full illumination mode on phosphate rich EST in the STR, producing 847.0 mg/L of dry cell mass containing 7.8%, w/w lipids, while when cultivated on phosphate limited EST, cell mass production was slightly lower but lipid biosynthesis was favored, with the lipid content reaching 24.7%, w/w in dry cell mass. In all trials, Nannochloropsis cell mass contained significant quantities of proteins and polysaccharides. Neutral lipids were predominant over polar lipids. Both glycolipid and phospholipid fractions were rich in polyunsaturated fatty acids, especially in eicosapentaenoic acid. We conclude that fish farm wastewaters can be re‐used as microalgae growth media, which is of financial and environmental importance.
Testimonial tips: How to make the most of your brand ambassadors
Authors: Talarico Donna
Published: August 2018

People trust their peers. For this reason, testimonials are a tried‐and‐true tactic for conveying your brand promise. Here, I'll share a few tips on gathering, editing, using, and reusing feedback from your students and alumni.
Rely on data to set, share strategy
Authors: Hope Joan
Published: August 2018

When MJ Knoll‐Finn, senior vice president for enrollment management at New York University, makes decisions about her unit's direction, she is guided by strategy and informed by data. And the same is true about the decisions that have guided her career.
CO2—H2O Capture and Cyclability on Sodium Cobaltate at Low Temperatures (30–80 °C): Experimental and Theoretical Analysis
Authors: Vera Elizabeth , Duan Yuhua , Pfeiffer Heriberto
Published: August 2018

Sodium cobaltate (NaCoO2) is analyzed for the CO2 cyclic carbonation–decarbonation process at low temperatures (30–80 °C) with relative humidity (RH) values between 0% and 80%, using water vapor as a catalytic intermediate. The presence of H2O clearly enhances the CO2 capture at T < 100 °C, compared with dry conditions, where the amount of CO2 captured increases as a function of RH. These improvements are attributed to the formation of NaHCO3 and Na2CO3 during carbonation. In the case of NaHCO3, water vapor becomes a part of carbonation, favoring reactivity. After the carbonation analysis, the decarbonation process is analyzed using a N2 flow, where results evidence that only NaHCO3 decomposition takes place at low temperatures, producing NaOH and CO2. This result indicates that NaCoO2 can be partially regenerated, suggesting a possible CO2 cyclic carbonation. CO2 carbonation–decarbonation tests are performed, confirming the cyclic capacity and stability. Moreover, the NaCoO2 sample is modified by adding different transition metals (Fe, Cu, and Ni) to improve CO2—H2O sorption under similar physicochemical conditions. Results indicate that Fe‐containing samples present the best properties. Finally, the effect of CO2 partial pressure on NaCoO2 and Fe‐containing samples is analyzed using similar RHs.
Spatiotemporal modeling of hydrological return levels: A quantile regression approach
Authors: Franco‐Villoria Maria , Scott Marian , Hoey Trevor
Published: August 2018

Extreme river flows can lead to inundation of floodplains, with consequent impacts for society, the environment, and the economy. Extreme flows are inherently difficult to model, being infrequent, irregularly spaced, and affected by nonstationary climatic controls. To identify patterns in extreme flows, a quantile regression approach can be used. This paper introduces a new framework for spatiotemporal quantile regression modeling, where the regression model is built as an additive model that includes smooth functions of time and space, as well as space–time interaction effects. The model exploits the flexibility that P‐splines offer and can be easily extended to incorporate potential covariates. We propose to estimate model parameters using a penalized least squares regression approach as an alternative to linear programming methods, classically used in quantile parameter estimation. The model is illustrated on a data set of flows in 98 rivers across Scotland.
How many measurements are required to construct an accurate sand budget in a large river? Insights from analyses of signal and noise
Authors: Grams Paul E. , Buscombe Daniel , Topping David J. , Kaplinski Matt , Hazel Joseph E.
Published: August 2018

Morphological change in river channels is frequently evaluated in the context of mass balance sediment budgets. In a closed sediment budget, measurements of sediment influx and efflux are coupled with measured changes in channel topography to provide both spatial and temporal resolution, and independent estimates of the mass balance. For sediment budgets constructed over long river segments (~102 channel widths or greater) and long periods (~2 years or longer), spatial and temporal accumulation of measurement uncertainty, compounded by inadequate sampling frequency or spatial coverage, may produce indeterminate results. The degree of indeterminacy may be evaluated in the context of a signal‐to‐noise ratio (SNR), which is a function of the magnitude of the mass balance and the magnitudes of potential systematic uncertainties associated with measurements and incomplete sampling. We report on a closed sand budget consisting of measurements of flux and two morphological surveys for a 50‐km segment of a large river over a 3‐year period. Accurate reporting of the magnitude and sign of the change in sand storage was only possible by using state‐of‐the‐art techniques with high temporal frequency and large spatial extent. Together, a sand flux and morphological mass balance revealed that sand evacuation was temporally concentrated (~100% of mass change occurred during 19% of the study period) and highly localized (70% of mass change occurred in 12% of the study segment). A SNR analysis revealed that uncertainty resulting from undersampling may approach or exceed that caused by measurement uncertainty and that daily sampling of suspended‐sand concentration or repeat mapping of at least 50% of the river segment was required to determine the sand budget with SNR > 1. The approach used here to analyze sand budget uncertainty is especially applicable to other river systems with large temporal variability in sediment transport and large spatial variability in erosion and deposition. © 2018 John Wiley & Sons, Ltd.
Temporal coding and rate remapping: Representation of nonspatial information in the hippocampus
Authors: Sanders Honi , Ji Daoyun , Sasaki Takuya , Leutgeb Jill K. , Wilson Matthew A. , Lisman John E.
Published: August 2018

Hippocampal place cells represent nonspatial information through a process called rate remapping, which involves a change in the firing rate of a place cell without changes in its spatial specificity. However, many hippocampal phenomena occur on very short time scales over which long‐term average firing rates are not an appropriate description of activity. To understand how rate remapping relates to fine‐scale temporal firing phenomena, we asked how rate remapping affected burst firing and trial‐to‐trial spike count variability. In addition, we looked at how rate remapping relates to the theta‐frequency oscillations of the hippocampus, which are thought to temporally organize firing on time scales faster than 100 ms. We found that theta phase coding was preserved through changes in firing rate due to rate remapping. Interestingly, rate remapping in CA1 in response to task demands preferentially occurred during the first half of the theta cycle. The other half of the theta cycle contained preferential expression of phase precession, a phenomenon associated with place cell sequences, in agreement with previous results. This difference of place cell coding during different halves of the theta cycle supports recent theoretical suggestions that different processes occur during the two halves of the theta cycle. The differentiation between the halves of the theta cycle was not clear in recordings from CA3 during rate remapping induced by task‐irrelevant sensory changes. These findings provide new insight into the way that temporal coding is utilized in the hippocampus and how rate remapping is expressed through that temporal code.
Cardiopulmonary resuscitation and first‐aid training of river users in Australia: A strategy for reducing drowning
Authors: Peden Amy E. , Franklin Richard C. , Leggat Peter A.
Published: August 2018

Issue addressed

Rivers are a leading location for fatal drowning worldwide, often geographically isolated from timely medical assistance. Cardiopulmonary resuscitation (CPR) benefits drowning victims and those who suffer cardiac arrests. This study explored CPR and first‐aid training of river users in Australia.

Methods

Adult river users (18+ years) were surveyed at four high‐risk river drowning sites. Respondents were asked the last time they undertook CPR (responses converted into: “CPR ever undertaken”—yes/no; and “CPR training current”—yes/no (training undertaken ≤12 months ago). Responses were explored by demographics and social determinants of health.

Results

Of those surveyed (N = 688), 98.4% responded regarding CPR. Seventy‐five percent (74.9%) had undertaken CPR training previously. Females and 35‐ to 44‐year‐olds were more likely to have undertaken training (P < 0.05). Males and older people (65+ years) were less likely to hold a current qualification (P < 0.05). Major city residents reported a longer mean time (5.4 years) since last trained than remote and very remote locations (2.0 years). People in low socio‐economic areas had a shorter time since qualification current (5.8 years) than those in areas deemed high (7.2 years).

Conclusion

Current CPR qualifications are important, particularly among those visiting high‐risk river drowning locations. System‐level, upstream strategies that should be explored include compulsory CPR training in secondary schools and linking CPR updates to motor vehicle licence renewals.

So what?

Cardiopulmonary resuscitation is a vital component of multifaceted river drowning prevention. Social determinants of health, such as socio‐economic disadvantage and geographical isolation, were not barriers to participation or currency of qualification.
PCNA‐associated factor P15PAF, targeted by FOXM1, predicts poor prognosis in high‐grade serous ovarian cancer patients
Authors: Jin Chengjuan , Liu Zhaojian , Li Yingwei , Bu Hualei , Wang Yu , Xu Ying , Qiu Chunping , Yan Shi , Yuan Cunzhong , Li Rongrong , Diao Nannan , Zhang Zhiwei , Wang Xiangxiang , Liu Lidong , Kong Beihua
Published: August 2018

Activation of the FOXM1 signaling pathway and the PI3K/AKT/mTOR signaling pathway is associated with poor prognosis in ovarian cancer. In this study, we demonstrated that P15PAF (KIAA0101) was significantly upregulated in high‐grade serous ovarian cancer (HGSOC) and that high KIAA0101 expression was associated with poor prognosis. FOXM1 transcriptionally activated KIAA0101 to drive proliferation and metastasis of ovarian cancer cells. KIAA0101 activated the PI3K/AKT/mTOR signaling pathway to inhibit cisplatin‐induced apoptosis and autophagy in ovarian cancer cells resulting in cisplatin resistance. Thus, KIAA0101 was closely related to the FOXM1 and PI3K/AKT/mTOR signaling pathways. Collectively, these findings provide insights into the mechanisms of poor prognosis of ovarian cancer and have implications for the development of both predictive and therapeutic biomarkers for the treatment of ovarian cancer.
Incidence of cervical intraepithelial neoplasia in women infected with human immunodeficiency virus (HIV) with no evidence of disease at baseline: Results of a prospective cohort study with up to 6.4 years of follow‐up from India
Authors: Joshi Smita , Muwonge Richard , Kulkarni Vinay , Deodhar Kedar , Mandolkar Mahesh , Lucas Eric , Sankaranarayanan Rengaswamy
Published: August 2018

We report the incidence of cervical intraepithelial neoplasia (CIN) among HIV‐infected women who did not have any colposcopic or histopathological evidence of CIN at baseline. Of the 1,023 women without any CIN at baseline, 855 (83.6%) have been followed up to a maximum of 6.4 years contributing 2,875 person years of observation (PYO). Among these 855 women, 54 cases of any CIN were observed resulting in incidence rate of any CIN of 1.9 per 100 PYO. The median time for follow‐up for women with any CIN was 3.0 (IQR 1.6–3.7) years. The cumulative incidence rate per 100 PYO of CIN 2 or worse lesion in women with HPV‐18 infection at baseline was 13.3% (95% CI 5.1–26.8); in women with HPV‐16 infection was 10.8% (95% CI 4.4–20.9); in women with HPV‐31 infection was 4.2% (95% CI 0.9–11.7); and in women with other high‐risk HPV infections was 5.4% (95% CI 2.6–9.7). HPV‐18 infection at baseline contributed highest frequency of incident CIN 2 or worse lesions followed by HPV‐16 infection; however, other high‐risk HPV types were also responsible for substantial number of incident CIN. The elevated risk of CIN2+ disease in the study cohort was non‐significant in women with CD4 count <200, possibly because of the small number of cases. Our results emphasize the need for regular cervical cancer screening of HIV‐infected women and urgent implementation of cervical cancer screening services in HIV programs in India and other low and middle‐income countries.
AIM2 deficiency reduces the development of hepatocellular carcinoma in mice
Authors: Martínez‐Cardona Claudia , Lozano‐Ruiz Beatriz , Bachiller Victoria , Peiró Gloria , Algaba‐Chueca Francisco , Gómez‐Hurtado Isabel , Such José , Zapater Pedro , Francés Rubén , González‐Navajas José Manuel
Published: August 2018

Chronic liver inflammation is crucial in the pathogenesis of hepatocellular carcinoma (HCC). Activation of the inflammasome complex is a key inflammatory process that has been associated with different liver diseases, but its role in HCC development remains largely unexplored. Here we analyzed the impact of different inflammasome components, including absent in melanoma 2 (AIM2) and NOD‐like receptor family pyrin domain containing 3 (NLRP3), in the development of diethylnitrosamine (DEN)‐induced HCC in mice. Genetic inactivation of AIM2, but not NLRP3, reduces liver damage and HCC development in this model. AIM2 deficiency ameliorates inflammasome activation, liver inflammation and proliferative responses during HCC initiation. We also identified that AIM2 is highly expressed in Kupffer cells, and that AIM2‐mediated production of IL‐1β by these cells is enhanced after DEN‐induced liver damage. Our data indicate that AIM2 promotes inflammation during carcinogenic liver injury and that it contributes to genotoxic HCC development in mice, thereby recognizing AIM2 as a potential therapeutic target in this disease.
Comparative analysis of transcervical resection and loop electrosurgical excision in the treatment of high‐grade cervical intraepithelial neoplasia
Authors: Chen Meizhuang , Cai Huihua , Chen Songqiang , Wu Xinyi , Ma Xiao , Liu Mubiao , Chen Le
Published: August 2018

Objective

To compare the efficacy of transcervical resection of the cervix (TCRC) and loop electrosurgical excision procedure (LEEP) in the treatment of high‐grade cervical squamous intraepithelial lesions (HSIL).

Methods

A retrospective case record review was conducted of patients with HSIL treated with TCRC or LEEP at Guangdong General Hospital, Guangdong Academy of Medical Sciences and Zhujiang Hospital, Guangzhou, China, from 2009 to 2015. The clinical characteristics, cone margin statuses, clinical outcomes, and adverse events were compared between the two groups.

Results

Among 647 included patients, 292 (45.1%) were treated with TCRC and 355 (54.9%) with LEEP. The incidences of positive margins, persistent and recurrent lesions, and intraoperative bleeding were lower in the TCRC group than in the LEEP group (P<0.001 for all comparisons). The rates of cervical adhesions were comparable between the two groups. During TCRC, 78 (26.7%) intrauterine lesions were diagnosed; most of these had been missed by transvaginal sonography.

Conclusion

TCRC may be an alternative method to LEEP in the treatment of HSIL. Compared with LEEP, TCRC has comparable clinical efficacy without additional adverse events. Moreover, TCRC is useful for detecting and/or removing intrauterine lesions during surgery.
A study of Cook Islands nurses' attitudes towards electronic medical records technology
Authors: Frank Jonathan , Salmona Michelle , Rivard Peter , Al‐Amin Mona
Published: August 2018

The Polynesian nurse prided herself on her ability to describe her patient's pain in a one‐page hand written note to her doctor. Now, the electronic medical records system was asking her to choose 1 to 10 on a drop down menu scale. This paper analyzed through a series of interviews what it is like for nurses in the remote Cook Islands to use Western‐designed medical information systems. Their experiences were examined through the lens of social construction of learning and cultural diffusion. Analysis of qualitative interview data suggested cultural as well as infrastructural barriers to engaged learning. Future researchers are advised to consider Facilitating Factors and Cultural Embeddedness constructs when considering technology adoption attitudes of medical practitioners in remote archipelago.
Mycobacterium tuberculosis: Surviving and Indulging in an Unwelcoming Host
Authors: Mishra Archita , Surolia Avadhesha
Published: August 2018

More than a century has passed since the identification of Mycobacterium tuberculosis (Mtb) as the causative agent of tuberculosis (TB), we still are nowhere close to eradicating this deadly disease. Moreover, emergence of new drug‐resistant strains has further complicated the situation, making it even more difficult to treat by conventional therapy regimens. Humans are the only reservoir for the existence and propagation of Mtb, which suggests that its latent forms will be most difficult to eradicate, till the human race lasts. Mtb has been associated with us for ages and its evolution is strictly guided to exploit its human host for survival and spread. The strategies employed by Mtb are unique and host specific, thereby making it hard to break this association without accurate understanding of this host‐pathogen interaction. Metabolic pathways have always been at the heart of Mtb pathogenesis, with a continuous cross‐talk between the pathogen and the host. Over the years, Mtb has mastered the art of manipulating the host machinery, along with modulating its own metabolism for survival in the hostile conditions. Here we aim to summarize the history of tuberculosis, its pathology and recent advances in basic understanding of the machinery, with eventual gape on the novel therapeutic strategies emerged in the past decade. © 2018 IUBMB Life, 70(9):917–925, 2018
Glucocorticoid‐Induced Autophagy Protects Osteocytes Against Oxidative Stress Through Activation of MAPK/ERK Signaling
Authors: Kar Rekha , Riquelme Manuel A. , Hua Rui , Jiang Jean X.
Published: August 2018

Autophagy confers protective or detrimental effects on cells depending on the cellular context. We showed here that oxidative stress‐induced cell death in osteocytic MLO‐Y4 cells coincided with decreased autophagy. Decreased autophagy was also observed in osteocytes of superoxide dismutase 1‐ (SOD1‐) deficient mice. Oxidative stress‐induced osteocyte death was exacerbated by an autophagy inhibitor, chloroquine, suggesting a protective function of basal autophagy levels against oxidative stress‐induced cell death. Pretreatment with dexamethasone reduced the susceptibility of osteocytes to oxidative stress‐induced cell death and conferred protection against TNFα/cycloheximide‐induced cell death. Inhibition of MAPK/ERK attenuated the formation of autophagosome, leading to increased osteocyte cell death. Taken together, our results suggest that autophagy, induced by moderate levels of glucocorticoids, leads to the preconditioning of osteocytes and conveys a novel cell‐protective function against cell death induced by oxidative stress and other insults. © 2018 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
Solving the riddle: Unraveling the mechanisms of blocking the binding of leukotoxin by therapeutic antagonists in periodontal diseases
Authors: Abdullahi Maryam , Olotu Fisayo A. , Soliman Mahmoud E.
Published: August 2018

Aggregatibacter actinomycetemcomitans is a Gram‐negative bacteria that has gained wide recognition for its causative role in the development of various immune diseases, which includes localized aggressive periodontitis. Its ability to evade host defense mechanisms is mediated by the secretion of leukotoxin (LtxA), which induces death of white blood cells (leukocytes) by specific binding to their surface‐expressed leukocyte function–associated receptor (LFA‐1) in its active state. Therapeutic compounds that interfere with this pathogenic process and abrogate A. actinomycetemcomitans virulence have been reported in literature. These include doxycycline, and more recently phytochemical compounds such as hamamelitanin, resveratrol, naringin, and quercetin. However, the question remains how do they work? Therefore, with the aid of computational tools, we explore the molecular mechanisms by which they possibly elicit their therapeutic functions. Molecular mechanics Poisson/Boltzmann surface area analyses revealed that these compounds bind favorably to active LFA‐1 with high affinity and considerable stability, indicative of their ability to occupy the LtxA binding site (LBS) and prevent LtxA binding. The conformational transition of open LFA‐1 to its closed state further describe the mechanistic activity of these compounds. In addition to notable reductions in structural mobility and flexibility, the burial of surface‐exposed interactive side chains at the LBS was observed, an occurrence that could alter the complementary binding of LtxA. It is also important to mention that these occurrences were induced more prominently by the phytochemicals. We believe that these findings will enhance the scope of drug design and discovery for potent LtxA antagonists with improved activities and therapeutic efficacies in the treatment of virulent A. actinomycetemcomitans diseases.
Retracted: Long noncoding RNA SNHG16 contributes to the development of bladder cancer via regulating miR‐98/STAT3/Wnt/β‐catenin pathway axis
Authors: Feng Feng , Chen Aiping , Huang Junjian , Xia Qinghua , Chen Yougen , Jin Xunbo
Published: August 2018

This study aimed to investigate the role and the possible mechanism of the long noncoding small nucleolar RNA host gene 16 (SNHG16) in bladder cancer development. The expression of SNHG16 in the tumor tissues and plasma of patients with bladder cancer as well as bladder cancer cell lines was detected. T24 cells were then transfected with sh‐SNHG16 to further investigate the effects of suppression of SNHG16 on T24 cell proliferation, apoptosis, migration, and invasion. In addition, the regulatory relationships between SNHG16 and miR‐98 as well as the target of miR‐98 were explored. Besides, the association between SNHG16 and the Wnt/β‐catenin pathway was further elucidated. The SNHG16 expression was upregulated in the tumor tissues and plasma of patients with bladder cancer, as well as bladder cancer cells. Suppression of SNHG16 inhibited T24 cell proliferation, promoted apoptosis, and suppressed migration and invasion in vitro. In addition, SNHG16 negatively regulated miR‐98 expression and regulated the malignant behaviors of T24 cells through sponging miR‐98. Moreover, signal transducer and activator of transcription 3 (STAT3) was identified as a functional target of miR‐98, and miR‐98 regulated the malignant behaviors of bladder cancer cells by targeting STAT3. Besides, suppression of SNHG16 inhibited the activation of the Wnt/β‐catenin pathway, which was further regulated by miR‐98 and STAT3, indicating that the effects of SNHG16/miR‐98/STAT3 on T24 cells were achieved through the Wnt/β‐catenin pathway. Our findings reveal that long noncoding RNAs SNHG16 is upregulated in bladder cancer and contributes to the development of bladder cancer possibly via regulating the miR‐98/STAT3/Wnt/β‐catenin pathway axis. The SNHG16/miR‐98/STAT3/Wnt/β‐catenin pathway axis may provide a new strategy for bladder cancer treatment.
Bidirectional regulation of adenosine 5′‐monophosphate–activated protein kinase activity by berberine and metformin in response to changes in ambient glucose concentration
Authors: Xiao Yuanyuan , Xu Miao , Alimujiang Miriayi , Bao Yuqian , Wei Li , Yin Jun
Published: August 2018

Both berberine and metformin are well‐known antihyperglycemic agents for diabetes treatment. Adenosine monophosphate (AMP)‐activated protein kinase (AMPK) activation is often considered as the most important molecular mechanism although the mechanism has been challenged recently. Up to now, when the ambient glucose level changes dynamically, the interaction between AMPK activity and the glucose‐lowering effects of the agents remains largely unknown. To address this issue, HepG2 hepatocytes and C2C12 myotubes were preincubated at normal (5.6 mM), moderate (15 mM), or high (30 mM) glucose concentrations followed by moderate‐glucose incubation plus berberine or metformin treatment. Preincubation at high glucose concentration followed by moderate‐glucose incubation activated the AMPK pathway, but the activation was abolished with berberine or metformin treatment. In contrast, alteration from normal glucose to moderate glucose concentration in the medium suppressed AMPK activity, which was activated by berberine or metformin. Both metformin and berberine decreased the intercellular adenosine triphosphate content, enhanced glucose consumption, and lactate release under all three preincubation glucose concentrations regardless of AMPK activity. In conclusion, AMPK activated by glucose reduction is inhibited by berberine or metformin. The elevation of glucose level led to suppressed AMPK activity, which was activated with the addition of agents. The potent glucose‐lowering effects with minimal hypoglycemia of berberine and metformin may be partially due to their bidirectional regulation of the AMPK signaling pathway. Berberine and metformin promote glucose metabolism via stimulation of glycolysis, which may not be related to AMPK activity.
Excreted‐secreted antigens of Toxoplasma gondii inhibit Foxp3 via IL‐2Rγ/JAK3/Stats pathway
Authors: Chen Jinling , Huang Caiqun , Zhu Dandan , Chen Liuting , Wang Jianxin , Sun Xiaolei , Hu Liang , Duan Yinong
Published: August 2018

Toxoplasma gondii excreted‐secreted antigens (ESA) could lead to the fetal abortion especially in the early stage of pregnancy. Deficit in regulatory T cells is a critical event in the fetal abortion. Transcription factor forkhead box p3 (Foxp3) mediates differentiation and functional roles on regulatory T cells. Previously, we revealed that ESA inhibited Foxp3 through the suppression of transforming growth factor‐β type II receptor, phosphorylation of Smad2, Smad3, and Smad4. Knockdown of Smad2 collaborated with ESA to further inhibit Foxp3. The decrease in Foxp3 caused by ESA reversed via forced expression of Smad2, Smad3, and Smad4, respectively. In this study, we investigate whether other signaling pathways are implicated in ESA‐induced Foxp3 downregulation. EL4 cells were cultured and stimulated with ESA. Interleukin‐2 receptor γ (IL‐2Rγ) chain, Janus kinase 3 (JAK3), signal transducer and activator of transcription 5 (Stat5), Stat3, phosphorylation of Stat5 and Stat3 were assayed by Western blot analysis. Phosphorylation of Stat5 and Stat3 was further measured by cellular immunofluorescence. The expression plasmid of pcDNA3.1‐Stat3 and pcDNA3.1‐Stat5b was constructed, respectively. The concentration of interleukin‐2 (IL‐2) in the culture supernatants was detected by enzyme‐linked immunosorbent assay. ESA inhibited the level of JAK3, phosphorylation of Stat5 and Stat3, and Foxp3 in EL4 cells. The suppressive effects of ESA on Foxp3 were attenuated by forced expression of Stat5 and Stat3. In addition, ESA suppressed IL‐2Rγ in EL4 cells, while IL‐2Rγ agonist could markedly reverse the diminished Foxp3 caused by ESA. Furthermore, ESA directly influenced the expression of IL‐2Rγ, rather than the availability of IL‐2 indirectly. ESA suppressed the level of Foxp3 via inhibiting IL‐2Rγ/JAK3/Stats signaling pathway in EL4 cells.
LncRNA CRNDE is a biomarker for clinical progression and poor prognosis in clear cell renal cell carcinoma
Authors: Ding Chenguang , Han Feng , Xiang Heli , Xia Xinxin , Wang Yuxiang , Dou Meng , Zheng Jin , Li Yang , Xue Wujun , Ding Xiaoming , Tian Puxun
Published: August 2018

Colorectal neoplasia differentially expressed (CRNDE) served as an oncogenic long noncoding RNA (lncRNA) to be involved in the initialization and development of human cancers. However, the clinical significance and biological function of CRNDE in clear cell renal cell carcinoma (ccRCC) was not fully understood. In our study, we found CRNDE levels were increased in ccRCC tissue specimens and cell lines, and corrected with advanced clinical stage, large tumor size, lymph node metastasis, distant metastasis, and poor pathological grade in patients with ccRCC. Furthermore, levels of CRNDE were negatively correlated with overall survival of patients with ccRCC, and high‐expression of CRNDE was an independent poor prognostic factor for patients with ccRCC. Moreover, loss‐of‐function and gain‐of‐function approaches showed CRNDE‐enhanced ccRCC cell migration and invasion through modulating EMT‐associated genes. In conclusion, CRNDE acts as an oncogenic lncRNA in ccRCC.
Interaction between epidermal growth factor receptor and interleukin‐6 receptor in NSCLC progression
Authors: Yuquan Bai , Hexiao Tang , Laiyi Wan , Gaofeng Pan , Xuefeng Zhou , Ming Xu , Yanhong Wei , Li Zhang , Jinping Zhao
Published: August 2018

Even though the interaction between epithelial growth factor receptor (EGFR) and interleukin‐6 receptor (IL‐6R) has been found in many tumors, there is a lack of relevant in‐depth study of lung cancer. The following study investigates the interaction of EGFR and IL‐6R in lung cancer. In the current study, EGFR, IL‐6, and glycoprotein 130 (GP130) were highly expressed in non–small cell lung cancer (NSCLC) tissue samples and were associated with clinicopathological features and poor prognosis of patients with NSCLC. Furthermore, the effect of EGF and IL‐6 on biological behavior of lung cancer cells (cell proliferation, invasion, cycle, and apoptosis) and the expression of EGFR, GP130, p‐protein kinase B (p‐AKT), and p‐p44/42 mitogen‐activated protein kinase (p‐p44/42 MAPK) was significantly stronger compared with other treatment groups (all P < 0.05). These results suggest that EGFR and IL‐6R have synergistic effects on NSCLC progression. This could help to solve the problem of EGFR inhibitors in the treatment of lung cancer resistance and improve the efficacy of current treatment for lung cancer through a combination of EGFR and IL‐6R signaling pathways.
Sodium tungstate: Is it a safe option for a chronic disease setting, such as diabetes?
Authors: Bertinat Romina , Westermeier Francisco , Gatica Rodrigo , Nualart Francisco
Published: August 2018

Diabetes is a complex metabolic disorder triggered by the deficient secretion of insulin by pancreatic β cells, the resistance of peripheral tissues to the action of the hormone, or both, and is characterized by chronic hyperglycemia leading to organ damage and failure. Tight glycemic control represents the best therapy to delay or stop progression of diabetes, with many antidiabetic drugs being commercially available nowadays. However, no ideal normoglycemic agent has been developed as yet, and those already available still induce hypoglycemia and/or weight gain as major side effects, worsening glycemic control. In this respect, the inorganic salt sodium tungstate (Na2WO4) has been proven to offer a good antidiabetic alternative in different animal models of diabetes, reducing body weight and normalizing glycemia without causing hypoglycemic episodes. The mechanisms of action mediating the potent antidiabetic actions but also the spectrum of undesirable effects of Na2WO4 are still poorly understood. In fact, along with its beneficial effects, Na2WO4 has been consistently reported to be toxic and even carcinogenic. Given that Na2WO4 is accumulated in the kidneys for elimination, here, we discuss a possible association between long‐term Na2WO4 treatment and a higher risk of renal carcinogenesis in diabetic individuals.
Heat shock protein 70: A promising therapeutic target for myocardial ischemia–reperfusion injury
Authors: Song Yan‐Jun , Zhong Chong‐Bin , Wang Xian‐Bao
Published: August 2018

Acute myocardial infarction is a major cause of death worldwide. The most important therapy for limiting ischemic injury and infarct size is timely and efficient myocardial reperfusion treatment, which may instead induce cardiomyocyte necrosis due to myocardial ischemia–reperfusion (I/R) injury. Heat shock protein 70 (HSP70), a stress‐inducible protein, is overexpressed during myocardial I/R. The induced HSP70 is shown to regulate several intracellular proteins (e.g., transcription factors, enzymes, and apoptosis‐related proteins) and signaling pathways (e.g., c‐Jun N‐terminal kinase pathway and extracellular‐signal‐regulated kinase 1/2 pathway), forming a complicated network that contributes to reducing reactive oxygen species accumulation, improving calcium homeostasis, inhibiting cellular apoptosis, thereby enhancing the stress adaption of myocardium to I/R injury. In addition, the extracellular HSP70, which is released from injured cardiomyocytes during I/R, acts as a proinflammatory mediator that results in cell death, while the intracellular HSP70 exerts antiinflammatory effects by suppressing proinflammatory signaling pathways. Notably, HSP70 is induced and contributes to the cardioprotection in several types of preconditioning and postconditioning. Meanwhile, it is shown that the cardioprotective effectiveness of preconditioning‐induced HSP70 (e.g., hyperthermia preconditioning‐induced HSP70) can be impaired by certain pathological conditions, such as hyperlipidemia and hyperglycemia. Thus, we highlight the widespread cardioprotective involvement of HSP70 in preconditioning and postconditioning and elucidate how HSP70‐mediated cardioprotection is impaired in these pathological conditions. Furthermore, several therapeutic potentials of HSP70 against myocardial I/R injury and potential directions for future studies are also provided in this review.
Identification and mapping of brain natriuretic peptide in the normal ventricular myocardium of a desert‐dwelling mammalian model, the camel (Camelus dromedarius): Immunohistochemical and ultrastructural study
Authors: Osman Abdel‐Hamid K. , Minamino Naoto , Marei Hany E.
Published: August 2018

Brain natriuretic peptide (BNP) is mainly produced in the ventricular myocardium, where it is released into the circulation, producing rapid volume decrease by diuresis, natriuresis, and water shift into the extracellular space, and vasodilation. The dromedary camel, a mammalian model of the desert nomads, lives under unfavorable physiological stresses during thirst, starvation, desiccation, and hot climate, thus has a special demand for water homeostasis. The present studies characterized BNP in the ventricular myocardium of healthy camels, immunohistochemically with a specific antibody, and ultrastructurally identified the endocrine property of the cardiomyocytes and Purkinje fibers. The paranuclear, granular, immunoreactive material was not restricted to the cardiomyocytes, as it was also visible in the Purkinje fibers and their associated nerve varicosities. The intensity of immunoreactive BNP showed a transmural gradient from the subepicardium to the myocardium. Intense immunoreactivity was also noted among the perivascular cardiomyocytes. At the electron microscopic level, specific granules were demonstrated in the paranuclear cytosol of cardiomyocytes and Purkinje fibers. The current study provides the first immunohistochemical localization pattern of BNP in the camel myocardium and suggests a relationship between the intense subepicardial BNP‐immunoexpression and a possible translocation of the active hormone to the pericardial fluid for further paracrine actions on the heart and its coronaries.
Differential regulation of estrogen in iron metabolism in astrocytes and neurons
Authors: Xu Manman , Tan Xu , Li Na , Wu Hao , Wang Yue , Xie Junxia , Wang Jun
Published: August 2018

Previous studies have demonstrated an effect of estrogen on iron metabolism in peripheral tissues. The role of estrogen on brain iron metabolism is currently unknown. In this study, we investigated the effect and mechanism of estrogen on iron transport proteins. We demonstrated that the iron exporter ferroportin 1 (FPN1) and iron importer divalent metal transporter 1 (DMT1) were upregulated and iron content was decreased after estrogen treatment for 12 hr in primary cultured astrocytes. Hypoxia‐inducible factor‐1 alpha (HIF‐1α) was upregulated, but HIF‐2α remained unchanged after estrogen treatment for 12 hr in primary cultured astrocytes. In primary cultured neurons, DMT1 was downregulated, FPN1 was upregulated, iron content decreased, iron regulatory protein (IRP1) was downregulated, but HIF‐1α and HIF‐2α remained unchanged after estrogen treatment for 12 hr. These results suggest that the regulation of iron metabolism by estrogen in astrocytes and neurons is different. Estrogen increases FPN1 and DMT1 expression by inducing HIF‐1α in astrocytes, whereas decreased expression of IRP1 may account for the decreased DMT1 and increased FPN1 expression in neurons.