bluuebunny/crossref_metadata_2025 huggingface dataset:
Climate-Related Distribution Shifts of Migratory Songbirds and Sciurids in the White Mountain National Forest
Authors: Van Tatenhove Aimee , Filiberti Emily , Sillett T. Scott , Rodenhouse Nicholas , Hallworth Michael
Published: January 2019

Climate change has been linked to distribution shifts and population declines of numerous animal and plant species, particularly in montane ecosystems. The majority of studies suggest both that low-elevation avian and small mammal species are shifting up in elevation and that high-elevation avian communities are either shifting further upslope or relocating completely with an increase in average local temperatures. However, recent research suggests numerous high elevation montane species are either not shifting or are shifting down in elevation despite the local increasing temperature trends, perhaps as a result of the increased precipitation at high elevations. In this study, we examine common vertebrate species distributions across the Hubbard Brook valley in the White Mountain National Forest, including resident and migratory songbirds and small mammals, in relation to historic spring temperature and precipitation. We found no directional change in distributions through time for any of the species. However, we show that the majority of low-elevation bird species in our study area respond to warm spring temperatures by shifting upslope. All bird species that shifted were long-distance migrants. Each low-elevation migrant species responded differently to warm spring temperatures, through upslope distribution expansion, downslope distribution contraction, or total distribution shift upslope. In contrast, we found a majority of high-elevation bird species and both high- and low-elevation mammal species did not shift in response to spring temperature or precipitation and may be subject to more complex climate trends. The heterogeneous response to climate change highlights the need for more comprehensive studies on the subject and careful consideration for appropriate species and habitat management plans in northeastern montane regions.
Nutrient and Bioactive Composition of Five Gabonese Forest Fruits and Their Potential Contribution to Dietary Reference Intakes of Children Aged 1–3 Years and Women Aged 19–60 Years
Authors: Fungo Robert , Muyonga John , Ngondi Judith , Mikolo-Yobo Christian , Iponga Donald , Ngoye Alfred , Nchuaji Tang Erasmus , Chupezi Tieguhong Julius
Published: January 2019

Widely consumed forest fruits in Gabon were analysed for nutrient and bioactive compositions and their potential contributions to meeting the nutrient requirements of consumers. Edible pulps of Panda oleosa Pierre, Gambeya lacourtiana (De Wild.) Aubrév. & Pellegr. and Poga oleosa Pierre contained substantial amounts of bioactive compounds; flavonoids (13.5–22.8 mg/100 g), proanthocyanins (2.4–7.6 mg/100 g), polyphenols (49.6–77.3 mg/100 g) and vitamin C (6.7–97.7 mg/100 g). The highest content of β-carotene (76.6 µg/100 g) was registered in fruits of Pseudospondias longifolia Engl. The fruits of P. oleosa had the highest essential minerals Fe, Zn and Se. If a child aged 1 to 3 years consumed about 200 g or if a non-lactating and non-pregnant woman consumed 300 g of Panda oleosa, Afrostyrax lepidophyllus Mildbr., G. lacourtiana, P. longifolia and Poga oleosa, they could obtain substantial DRI ranging between 20–100% for energy, vitamins C and E, iron, magnesium, iron and zinc. Forest fruits can considerably contribute towards the human nutrient requirements. Based on the results of this study, forest foods should be considered in formulating policies governing food and nutrition security in Gabon.
Workshop Summary “The Power of Faraday Tomography”
Authors: Haverkorn Marijke , Machida Mami , Akahori Takuya
Published: January 2019

This article summarizes the work presented at the workshop “The Power of Faraday Tomography: towards 3D mapping of cosmic magnetic fields”, held in Miyazaki, Japan, in Spring 2018. We place the various oral and poster presentations given at the workshop in a broader perspective and present some highlight results from every presenter.
The Wisdom of and Science behind Indigenous Cultural Practices
Authors: Borunda Rose , Murray Amy
Published: January 2019

Conquest and colonization have systematically disrupted the processes by which Indigenous communities of the Americas transmit cultural knowledge and practices from one generation to the next. Even today, the extended arm of conquest and colonization that sustain oppression and culturicide continue to inflict trauma upon Indigenous people. Yet, current scientific research now attests to how Indigenous cultural practices promote healing and well-being within physical as well as mental health domains. This examination addresses Indigenous cultural practices related to storytelling, music, and dance. In drawing from evidence-based research, the case is made for not only restoring these practices where they have been disrupted for Indigenous people but that they have value for all people. The authors recommend reintroducing their use as a means to promote physical, spiritual, and mental well-being while recognizing that these practices originated from and exist for Indigenous people.
Systematic Review of Pain in Clinical Practice Guidelines for Management of COPD: A Case for Including Chronic Pain?
Authors: Lewthwaite Hayley , Williams Georgia , Baldock Katherine L. , Williams Marie T.
Published: January 2019

Chronic pain is highly prevalent and more common in people with chronic obstructive pulmonary disease (COPD) than people of similar age/sex in the general population. This systematic review aimed to describe how frequently and in which contexts pain is considered in the clinical practice guidelines (CPGs) for the broad management of COPD. Databases (Medline, Scopus, CiNAHL, EMbase, and clinical guideline) and websites were searched to identify current versions of COPD CPGs published in any language since 2006. Data on the frequency, context, and specific recommendations or strategies for the assessment or management of pain were extracted, collated, and reported descriptively. Of the 41 CPGs (English n = 20) reviewed, 16 (39%) did not mention pain. Within the remaining 25 CPGs, pain was mentioned 67 times (ranging from 1 to 10 mentions in a single CPG). The most frequent contexts for mentioning pain were as a potential side effect of specific pharmacotherapies (22 mentions in 13 CPGs), as part of differential diagnosis (14 mentions in 10 CPGs), and end of life or palliative care management (7 mentions in 6 CPGs). In people with COPD, chronic pain is common; adversely impacts quality of life, mood, breathlessness, and participation in activities of daily living; and warrants consideration within CPGs for COPD.
Desaturation during Six-Minute Walk Testing Predicts Major Morbidity Following Anatomic Lung Resection among Patients with COPD
Authors: Towe Christopher W. , Wu Katherine , Khil Alina , Perry Yaron , Worrell Stephanie G. , Ho Vanessa P. , Linden Philip A.
Published: January 2019

Background: Pulmonary function testing (PFT) is commonly used to risk-stratify patients prior to lung resection. Guidelines recommend that patients with reduced lung function, due to chronic lung conditions such as Chronic Obstructive Pulmonary Disease (COPD), should receive additional physiologic testing to determine fitness for resection. We reviewed our experience with six-minute walk testing (SMWT) to determine the association of test results and post-operative complications. Methods: Consecutive adult patients undergoing segmentectomy, lobectomy, bilobectomy or pneumonectomy between 1 January, 2007 and 1 January, 2017 were identified in a prospectively maintained database. Patients with poor lung function, as defined by percent predicted forced expiratory volume in 1 s (FEV1) or diffusion capacity of carbon monoxide (DLCO) ≤60%, had results of SMWT extracted from their chart. Association of test result to post-operative events was performed. Results: 581 patients had anatomic lung resections with predicted post-operative FEV1 or DLCO values ≤60%, consistent with a diagnosis of COPD. Among them, 50 (8.6%) had preoperative SMWT performed. Patients who received SMWT were more likely to have a FEV1 or DLCO less than 40 percent predicted (24/50 (48.0%) vs 166/531 (31.3%), p = 0.016). Post-operatively, patients who had SMWT performed had higher rates of pneumonia, but similar rates of major morbidity. The post-exercise oxygen saturation and the amount of desaturation correlated with the occurrence of major morbidity. In multivariable regression, oxygen desaturation was an independent risk factor for the occurrence of major morbidity, and desaturation was an excellent predictor of major morbidity by receiver operating characteristic curves analsysis. Conclusions: Among patients with elevated risk, oxygen desaturation during SMWT was independently associated with the occurence of major morbidity in multivariable analysis, while pulmonary function testing was not. SMWT is an important tool for risk-stratification, and may be underutilized.
Atlantis: A Grain of Truth Behind the Fiction?
Authors: Rapisarda Massimo
Published: January 2019

The legend of Atlantis was almost certainly invented by Plato to promote the political ideal of his masterwork The Republic, while praising the heroism of his own ancestors. This paper suggests that, in assembling the story, Plato might have reworked the myth of the foundation of Egypt—attributed to divine invaders bringing agriculture and unknown technologies to the country—and popularized in Greece through the writings of Herodotus. The key issue explored is the curious coincidence between the period of the alleged foundation of Egypt (according to traditional Egyptian sources) and some remarkable events that characterized the end of the Ice Age. Indeed, besides the sudden increase in temperature and the consequent rise in sea level, the period was also marked by the birth of agriculture and the appearance of totally new technologies in diverse Near Eastern locations. The memory of these events would have been handed down through the myth of the foundation of Egypt, and through this, to Greek culture, enabling Plato to exaggerate the antiquity of his noble ancestors, while embellishing the characteristics of the invaders. Such occasional technological leaps may also have occurred elsewhere in the world, for instance on the deltas of the Indus or the Yangtze, driven by the same change in climate that affected the whole planet. Although today there is no archaeological evidence of such events besides in the Near East, the article suggests that the possible discovery of obsidian in a submerged site would be a strong indication of a local technological leap. To this end it examines, as a Mediterranean example, some flooded islands in the Strait of Sicily, which, lying on the route to Pantelleria, may retain traces of ancient obsidian exploitation.
Structure of the Granitic Pegmatite Field of the Northern Coast of Portugal—Inner Pegmatite Structures and Mineralogical Fabrics
Authors: Faria Cristiana , Leal Gomes Carlos
Published: January 2019

On the coastline of Northern Portugal, metamorphic formations and pegmatites were the subject of structural analysis with the main goal of understanding Variscan kinematics and related pegmatite intrusion. This study also aims to discriminate, select and characterize relevant aspects of the structure and the paragenesis of pegmatites, well exposed as a result of coastal erosion, justifying its inclusion in the geological heritage of the Northern coast of Portugal. The pegmatite bodies show distinctive internal and external structures that are attributable to different modes of emplacement and subsequent deformation. The pegmatitic implantation in the areas of Moledo and Afife occurs in an intragneissic and perigranitic environment, for the first area, and perigneissic and perigranitic environment, for the second. In Pedras Ruivas predominates the implantation into an exo-gneissic to exo-granitic domain. The Moledo veins show evidence of multiphase open/filling, revealing positions, shapes, attitudes, sizes and internal structures that change as a function of the host lithology and host structure, but mainly due to the dilation and the cycles number of local telescoping. The structural analysis of the pegmatite bodies allows the deduction of a local fulcrum of expansion that hypothetically overlaps a hidden stock of parental granite. In Afife and Pedras Ruivas, some pegmatitic lenses are specialized and mineralized in Li, Cs and Ta, with spodumene and tantalite ± cassiterite. Spodumene occurs as giant crystals, centimetric to pluri-decimetric in length, which mark very clearly the structures of in situ or in flow crystallization inside the pegmatites (primary structures) and also the secondary structures resulting from deformation. The geometric analysis of fabrics helps the individualization of well-defined stages of progressive evolution of the deformation of the pegmatites, allowing its correlation with major D2–D3 episodes of regional Variscan deformation.
Roman Wine in Barbaricum. Preliminary Studies on Ancient Wine Recreation
Authors: Feier Iwona , Migała Aleksandra , Pietruszka Marta , Jackowski Mateusz
Published: January 2019

Ancient Roman wine is found outside of the borders of the Roman world as a result of the Roman influence, trade and political relations. In our project, we decided to extensively research and recreate the ancient method of wine making in order to understand ancient viticulture and viniculture as it could have been if implemented outside of the borders. The objective was to recreate roman wine using ancient methods based on ancient texts (such as Columella, Pliny the Elder, Cicero, Cato the Elder, Galenus and Mago). The wine was made using modern grapes grown on lands considered by the Romans as barbaric (i.e., outside the Roman Limes), in modern Poland. The aim of the project—except for the wine making itself—was to measure the level of alcohol created through fermentation process. Ethanol levels in samples were obtained using gas chromatography (GC).
A Correlation–Scale–Threshold Method for Spatial Variability of Rainfall
Authors: Sivakumar Bellie , Woldemeskel Fitsum , Vignesh Rajendran , Jothiprakash Vinayakam
Published: January 2019

Rainfall data at fine spatial resolutions are often required for various studies in hydrology and water resources. However, such data are not widely available, as their collection is normally expensive and time-consuming. A common practice to obtain fine-spatial-resolution rainfall data is to employ interpolation schemes to derive them based on data available at nearby locations. Such interpolation schemes are generally based on rainfall correlation or distance between stations. The present study proposes a combined rainfall correlation-spatial scale-correlation threshold method for representing spatial rainfall variability. The method is applied to monthly rainfall data at a resolution of 0.25° × 0.25° latitude/longitude across Australia, available from the Tropical Rainfall Measuring Mission (TRMM 3B43 version). The results indicate that rainfall dynamics in northern and northeastern Australia have far greater spatial correlations when compared to the other regions, especially in southern and southeastern Australia, suggesting that tropical climates generally have greater spatial rainfall correlations when compared to temperate, oceanic, and continental climates, subject to other influencing factors. The implications of the outcomes for rainfall data interpolation and the rain gauge monitoring network are also discussed, especially based on results obtained for ten major cities in Australia.
Estimation of the Ecological Fallacy in the Geographical Analysis of the Association of Socio-Economic Deprivation and Cancer Incidence
Authors: Lokar Katarina , Zagar Tina , Zadnik Vesna
Published: January 2019

Ecological deprivation indices at the level of spatial units are often used to measure and monitor inequalities in health despite the possibility of ecological fallacy. For the purpose of this study, the European Deprivation Index (EDI) was used, which is based on Townsend theorization of relative deprivation. The Slovenian version of EDI (SI-EDI) at the aggregated level (SI-EDI-A) was calculated to the level of the national assembly polling stations. The SI-EDI was also calculated at the individual level (SI-EDI-I) by the method that represents a methodological innovation. The degree of ecological fallacy was estimated with the Receiver Operating Characteristics (ROC) curves. By calculating the area under the ROC curve, the ecological fallacy was evaluated numerically. Agreement between measuring deprivation with SI-EDI-A and SI-EDI-I was analysed by graphical methods and formal testing. The association of the socio-economic status and the cancer risk was analysed in all first cancer cases diagnosed in Slovenia at age 16 and older in the period 2011–2013. Analysis was done for each level separately, for SI-EDI-I and for SI-EDI-A. The Poisson regression model was implemented in both settings but adapted specifically for aggregated and individual data. The study clearly shows that ecological fallacy is unavoidable. However, although the association of cancer incidence and socio-economic deprivation at individual and aggregated levels was not the same for all cancer sites, the results were very similar for the majority of investigated cancer sites and especially for cancers associated with unhealthy lifestyles. The results confirm the assumptions from authors’ previous research that using the level of the national assembly polling stations would be the acceptable way to aggregate data when explaining inequalities in health in Slovenia in ecological studies.
Driving Anger, Aberrant Driving Behaviors, and Road Crash Risk: Testing of a Mediated Model
Authors: Zhang Tingru , Chan Alan H. S. , Xue Hongjun , Zhang Xiaoyan , Tao Da
Published: January 2019

With the dramatic increase in motorization, road traffic crashes have become the leading cause of death in China. To reduce the losses associated with road safety problems, it is important to understand the risk factors contributing to the high crash rate among Chinese drivers. This study investigated how driving anger and aberrant driving behaviors are related to crash risk by proposing and testing one mediated model. In this model, the effects of driving anger on road crash risk were mediated by aberrant driving behaviors. However, unlike previous studies, instead of using the overall scale scores, the subscales of driving anger and aberrant driving behaviors were used to establish the mediated model in this study. To test the validity of this model, an Internet-based questionnaire, which included various measures of driving anger, aberrant driving, and road crash history, was completed by a sample of 1974 Chinese drivers. The results showed that the model fitted the data very well and aberrant driving behaviors fully mediated the effects of driving anger on road crash risk. Findings from the present study are useful for the development of countermeasures to reduce road traffic crashes in China.
Building Back Better: Local Health Department Engagement and Integration of Health Promotion into Hurricane Harvey Recovery Planning and Implementation
Authors: Kennedy Mallory , Gonick Shannon , Meischke Hendrika , Rios Janelle , Errett Nicole A.
Published: January 2019

Disaster recovery provides an opportunity to build healthier and more resilient communities. However, opportunities and challenges encountered by local health departments (LHDs) when integrating health considerations into recovery have yet to be explored. Following Hurricane Harvey, 17 local health and emergency management officials from 10 agencies in impacted Texas, USA jurisdictions were interviewed to describe the types and level of LHD engagement in disaster recovery planning and implementation and the extent to which communities leveraged recovery to build healthier, more resilient communities. Interviews were conducted between December 2017 and January 2018 and focused on if and how their communities were incorporating public health considerations into the visioning, planning, implementation, and assessment phases of disaster recovery. Using a combined inductive and deductive approach, we thematically analyzed interview notes and/or transcripts. LHDs reported varied levels of engagement and participation in activities to support their community’s recovery. However, we found that LHDs rarely articulated or informed decision makers about the health impacts of recovery activities undertaken by other sectors. LHDs would benefit from additional resources, support, and technical assistance designed to facilitate working across sectors and building resilience during recovery.
Clinical, Neuroimaging, and Neurophysiological Findings in Children with Microcephaly Related to Congenital Zika Virus Infection
Authors: C. Lage Maria-Lucia , Carvalho Alessandra L. de , Ventura Paloma A. , Taguchi Tania B. , Fernandes Adriana S. , Pinho Suely F. , Santos-Junior Onildo T. , Ramos Clara L. , Nascimento-Carvalho Cristiana M.
Published: January 2019

Zika virus (ZIKV) infection appeared in Brazil in 2015, causing an epidemic outbreak with increased rates of microcephaly and other serious birth disorders. We reviewed 102 cases of children who were diagnosed with microcephaly at birth and who had gestational exposure to ZIKV during the outbreak. We describe the clinical, neuroimaging, and neurophysiological findings. Most mothers (81%) reported symptoms of ZIKV infection, especially cutaneous rash, during the first trimester of pregnancy. The microcephaly was severe in 54.9% of the cases. All infants presented with brain malformations. The most frequent neuroimaging findings were cerebral atrophy (92.1%), ventriculomegaly (92.1%), malformation of cortical development (85.1%), and cortical–subcortical calcifications (80.2%). Abnormalities in neurological exams were found in 97.0% of the cases, epileptogenic activity in 56.3%, and arthrogryposis in 10.8% of the infants. The sensorineural screening suggested hearing loss in 17.3% and visual impairment in 14.1% of the infants. This group of infants who presented with microcephaly and whose mothers were exposed to ZIKV early during pregnancy showed clinical and radiological criteria for congenital ZIKV infection. A high frequency of brain abnormalities and signs of early neurological disorders were found, and epileptogenic activity and signs of sensorineural alterations were common. This suggests that microcephaly can be associated with a worst spectrum of neurological manifestations.
An Improved Empirical Model for Flood Discharge Atomization and Its Application to Optimize the Flip Bucket of the Nazixia Project
Authors: Lian Jijian , He Junling , Liu Fang , Ran Danjie , Wang Xiaoqun , Wang Chang
Published: January 2019

Flood discharge atomization is a serious challenge that threatens the daily lives of the residents around the dam area as well as the safety of the water conservancy project. This research aims to improve the prediction accuracy of the stochastic splash model. A physical model test with four types of flip bucket is conducted to obtain the hydraulic parameters of the impinging outer edge of the water jet, the relationship of the splashing droplet diameter with its corresponding velocity, and the spatial distribution of the downstream nappe wind. The factors mentioned above are introduced to formulate the empirical model. The rule obtained from the numerical analyses is compared with the results of the physical model test and the prototype observations, which yields a solid agreement. The numerical results indicate that the powerhouse is no longer in the heavy rain area when adopting the flip bucket whose curved surface is attached to the left wall. The rainfall intensity of the powerhouse is significantly weaker than that of other types under the designed condition, so we choose it as the recommended bucket type. Meanwhile, we compare the rainfall intensity distribution of the original bucket and the recommended bucket under different discharge which rates ranging from 150.71 to 1094.9 m3/s. It is found that the powerhouse and the owner camp are no longer in the heavy rain area under all of the working conditions. Finally, it is shown that the atomization influence during the flood discharge can be reduced by using the recommended bucket.
Hip Osteoarthritis and Physical Workload: Influence of Study Quality on Risk Estimations—A Meta-Analysis of Epidemiological Findings
Authors: Sun Yi , Nold Annette , Glitsch Ulrich , Bochmann Frank
Published: January 2019

In this paper, we critically evaluate the quality of epidemiological evidence on hip osteoarthritis and workload published so far. The influence of study quality on risk estimations was analyzed in sensitivity meta-analyses and meta-regression analyses. Comprehensive searches for epidemiological studies of hip osteoarthritis and occupational workload were performed in literature databases and current reviews. All studies were assessed on the basis of study design, defined quality scores, and relevant confounders considered. In total, 34 suitable studies were identified for critical evaluation. Of these, 20 are prevalence studies and 14 incidence studies. Strong heterogeneity is observed in study design, quality level, and estimated exposure parameters. A consistent positive association between heavy physical workload and hip osteoarthritis was observed only among the male populations, not among the female populations. In general, cohort studies provided lower effect estimates than cross-sectional and population-based case-control studies. Studies with high quality scores also produced lower effect estimates than studies with low quality scores. Consideration of BMI as a confounder in published studies also yielded lower effect estimates than studies without consideration of BMI as a confounder. Our analyses indicate that high-quality studies of the association between occupational workload and hip osteoarthritis provide lower effect estimates than studies of lower quality.
The Risk of Stroke in Kidney Transplant Recipients with End-Stage Kidney Disease
Authors: Huang Shih-Ting , Yu Tung-Min , Chuang Ya-Wen , Chung Mu-Chi , Wang Chen-Yu , Fu Pin-Kuei , Ke Tai-Yuan , Li Chi-Yuan , Lin Cheng-Li , Wu Ming-Ju , Kao Chia-Hung
Published: January 2019

Background: The incidence of stroke after kidney transplantation is poorly understood. Our study aimed to determine the incidence and predictors of stroke as well as mortality from stroke in kidney transplant recipients (KTRs). Methods: This retrospective cohort study used the National Health Insurance Research Database in Taiwan to study KTRs (N = 4635), patients with end-stage renal disease (ESRD; N = 69,297), and patients from the general population who were chronic kidney disease (CKD)-free and matched by comorbidities (N = 69,297) for the years 2000 through 2010. The risk of stroke was analyzed using univariate and multivariate Cox regression models and compared between study cohorts. Findings: Compared with the ESRD subgroup, KTRs had a significantly lower risk of overall stroke (adjusted hazard ratio (aHR) = 0.37, 95% confidence interval (CI) = 0.31–0.44), ischemic stroke (aHR = 0.45, 95% CI = 0.37–0.55), and hemorrhagic stroke (aHR = 0.20, 95% CI = 0.14–0.29). The risk patterns for each type of stroke in the KTR group were not significantly different than those of the CKD-free control subgroup. The predictors of stroke were age and diabetes in KTRs. All forms of stroke after transplantation independently predicted an increased risk of subsequent mortality, and the strongest risk was related to hemorrhagic events. Interpretation: KTRs had a lower risk of stroke than ESRD patients, but this risk was not significantly different from that of the CKD-free comorbidities-matched general population group. Although stroke was relatively uncommon among cardiovascular events, it predicted unfavorable outcome in KTRs.
Endothelial Cells Tissue-Specific Origins Affects Their Responsiveness to TGF-β2 during Endothelial-to-Mesenchymal Transition
Authors: Ursoli Ferreira Fernanda , Eduardo Botelho Souza Lucas , Hassibe Thomé Carolina , Tomazini Pinto Mariana , Origassa Clarice , Salustiano Suellen , Marcel Faça Vitor , Olsen Câmara Niels , Kashima Simone , Tadeu Covas Dimas
Published: January 2019

The endothelial-to-mesenchymal transition (EndMT) is a biological process where endothelial cells (ECs) acquire a fibroblastic phenotype after concomitant loss of the apical-basal polarity and intercellular junction proteins. This process is critical to embryonic development and is involved in diseases such as fibrosis and tumor progression. The signaling pathway of the transforming growth factor β (TGF-β) is an important molecular route responsible for EndMT activation. However, it is unclear whether the anatomic location of endothelial cells influences the activation of molecular pathways responsible for EndMT induction. Our study investigated the molecular mechanisms and signaling pathways involved in EndMT induced by TGF-β2 in macrovascular ECs obtained from different sources. For this purpose, we used four types of endothelial cells (coronary artery endothelial cells, CAECs; primary aortic endothelial cells PAECs; human umbilical vein endothelia cells, HUVECs; and human pulmonary artery endothelial cells, HPAECs) and stimulated with 10 ng/mL of TGF-β2. We observed that among the ECs analyzed in this study, PAECs showed the best response to the TGF-β2 treatment, displaying phenotypic changes such as loss of endothelial marker and acquisition of mesenchymal markers, which are consistent with the EndMT activation. Moreover, the PAECs phenotypic transition was probably triggered by the extracellular signal–regulated kinases 1/2 (ERK1/2) signaling pathway activation. Therefore, the anatomical origin of ECs influences their ability to undergo EndMT and the selective inhibition of the ERK pathway may suppress or reverse the progression of diseases caused or aggravated by the involvement EndMT activation.
Vanillic Acid Suppresses HIF-1α Expression via Inhibition of mTOR/p70S6K/4E-BP1 and Raf/MEK/ERK Pathways in Human Colon Cancer HCT116 Cells
Authors: Gong Jingli , Zhou Shengxue , Yang Shihai
Published: January 2019

Hypoxia-inducible factor 1 (HIF-1) plays a pivotal role in tumor adaptation to microenvironmental hypoxia, and it also exerts important roles in angiogenesis and tumor development. Vanillic acid is a dietary phenolic compound reported to exhibit anticancer properties. However, the mechanisms by which vanillic acid inhibits tumor growth are not fully understood. Here, we investigated the effect of vanillic acid on HIF-1α activation. Vanillic acid significantly inhibits HIF-1α expression induced by hypoxia in various human cancer cell lines. Further analysis revealed that vanillic acid inhibited HIF-1α protein synthesis. Neither the HIF-1α protein degradation rate nor the steady-state HIF-1α mRNA levels were affected by vanillic acid. Moreover, vanillic acid inhibited HIF-1α expression by suppressing mammalian target of rapamycin/p70 ribosomal protein S6 kinase/eukaryotic initiation factor 4E-binding protein-1 and Raf/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK pathways. We found that vanillic acid dose-dependently inhibited VEGF and EPO protein expressions and disrupted tube formation. The results suggest that vanillic acid effectively inhibits angiogenesis. Flow cytometry analysis demonstrated that vanillic acid significantly induced G1 phase arrest and inhibited the proliferation of human colon cancer HCT116 cells. In vivo experiments confirmed that vanillic acid treatment caused significant inhibition of tumor growth in a xenografted tumor model. These studies reveal that vanillic acid is an effective inhibitor of HIF-1α and provides new perspectives into the mechanism of its antitumor activity.
Pioglitazone-Primed Mesenchymal Stem Cells Stimulate Cell Proliferation, Collagen Synthesis and Matrix Gene Expression in Tenocytes
Authors: Kim Won , Lee Seul Ki , Kwon Young-Won , Chung Sun G. , Kim Soo
Published: January 2019

Various therapeutic effects of mesenchymal stem cells (MSCs) have been reported. However, the rapid clearance of these cells in vivo, difficulties in identifying their therapeutic mechanism of action, and insufficient production levels remain to be resolved. We investigated whether a pioglitazone pre-treatment of MSCs (Pio-MSCs) would stimulate the proliferation of co-cultured tenocytes. Pioglitazone increased the proliferation of MSCs and enhanced the secretion of VEGF (vascular endothelial growth factor) and collagen in these cells. We then examined the effects of Pio-MSCs on tenocytes using an indirect transwell culture system. A significant increase in tenocyte proliferation and cell cycle progression was observed in these co-cultures. Significant increases were observed in wound scratch closure by tenocytes from a Pio-MSC co-culture. Pio-MSCs also enhanced the secretion of collagen from tenocytes. A higher mRNA level of collagen type 1 (Col 1) and type 3 (Col 3), scleraxis (Scx), and tenascin C (TnC) was found in the tenocytes in Pio-MSC co-cultures compared with monocultured cells or tenocytes cultured with non-treated MSCs. Our results indicate that pioglitazone enhances the therapeutic effects of MSCs on tendon repair.
An Overview on Streptococcus bovis/Streptococcus equinus Complex Isolates: Identification to the Species/Subspecies Level and Antibiotic Resistance
Authors: Pompilio Arianna , Di Bonaventura Giovanni , Gherardi Giovanni
Published: January 2019

Streptococcus bovis/Streptococcus equinus complex (SBSEC), a non-enterococcal group D Streptococcus spp. complex, has been described as commensal bacteria in humans and animals, with a fecal carriage rate in humans varying from 5% to over 60%. Among streptococci, SBSEC isolates represent the most antibiotic-resistant species—with variable resistance rates reported for clindamycin, erythromycin, tetracycline, and levofloxacin—and might act as a reservoir of multiple acquired genes. Moreover, reduced susceptibility to penicillin and vancomycin associated with mobile genetic elements have also been detected, although rarely. Since the association of SBSEC bacteremia and colon lesions, infective endocarditis and hepatobiliary diseases has been established, particularly in elderly individuals, an accurate identification of SBSEC isolates to the species and subspecies level, as well as the evaluation of antibiotic resistance, are needed. In this paper, we reviewed the major methods used to identify SBSEC isolates and the antimicrobial resistance rates reported in the scientific literature among SBSEC species.
Interplay of Auxin and Cytokinin in Lateral Root Development
Authors: Jing Hongwei , Strader Lucia C.
Published: January 2019

The spacing and distribution of lateral roots are critical determinants of plant root system architecture. In addition to providing anchorage, lateral roots explore the soil to acquire water and nutrients. Over the past several decades, we have deepened our understanding of the regulatory mechanisms governing lateral root formation and development. In this review, we summarize these recent advances and provide an overview of how auxin and cytokinin coordinate the regulation of lateral root formation and development.
Zn2+ Aggravates Tau Aggregation and Neurotoxicity
Authors: Li Xuexia , Du Xiubo , Ni Jiazuan
Published: January 2019

Alzheimer’s disease (AD) is a neurodegenerative disease with high morbidity that has received extensive attention. However, its pathogenesis has not yet been completely elucidated. It is mainly related to β-amyloid protein deposition, the hyperphosphorylation of tau protein, and the loss of neurons. The main function of tau is to assemble tubulin into stable microtubules. Under pathological conditions, tau is hyperphosphorylated, which is the major component of neurofibrillary tangles (NFT) in AD. There is considerable evidence showing that the dyshomeostasis of Zn2+ is closely related to the development of AD. Herein, by using the third repeat unit of the microtubule-binding domain of tau (tau-R3), we investigated the effect of Zn2+ on the aggregation and neurotoxicity of tau. Experimental results showed that tau-R3 probably bound Zn2+ via its Cys residue with moderate affinity (association constant (Ka) = 6.82 ± 0.29 × 104 M−1). Zn2+ accelerated tau-R3 aggregation and promoted tau-R3 to form short fibrils and oligomers. Compared with tau-R3, Zn2+-tau-R3 aggregates were more toxic to Neuro-2A (N2A) cells and induced N2A cells to produce higher levels of reactive oxygen species (ROS). The dendrites and axons of Zn2+-tau-R3-treated neurons became fewer and shorter, resulting in a large number of neuronal deaths. In addition, both tau-R3 and Zn2+-tau-R3 aggregates were found to be taken up by N2A cells, and more Zn2+-tau-R3 entered the cells compared with tau-R3. Our data demonstrated that Zn2+ can aggravate tau-R3 aggregation and neurotoxicity, providing clues to understand the relationship between Zn2+ dyshomeostasis and the etiology of Alzheimer’s disease.
VEGF/Neuropilin Signaling in Cancer Stem Cells
Authors: Mercurio Arthur M.
Published: January 2019

The function of vascular endothelial growth factor (VEGF) in cancer extends beyond angiogenesis and vascular permeability. Specifically, VEGF-mediated signaling occurs in tumor cells and this signaling contributes to key aspects of tumorigenesis including the self-renewal and survival of cancer stem cells (CSCs). In addition to VEGF receptor tyrosine kinases, the neuropilins (NRPs) are critical for mediating the effects of VEGF on CSCs, primarily because of their ability to impact the function of growth factor receptors and integrins. VEGF/NRP signaling can regulate the expression and function of key molecules that have been implicated in CSC function including Rho family guanosine triphosphatases (GTPases) and transcription factors. The VEGF/NRP signaling axis is a prime target for therapy because it can confer resistance to standard chemotherapy, which is ineffective against most CSCs. Indeed, several studies have shown that targeting either NRP1 or NRP2 can inhibit tumor initiation and decrease resistance to other therapies.
Cell-Free Protein Synthesis Using S30 Extracts from Escherichia coli RFzero Strains for Efficient Incorporation of Non-Natural Amino Acids into Proteins
Authors: Adachi Jiro , Katsura Kazushige , Seki Eiko , Takemoto Chie , Shirouzu Mikako , Terada Takaho , Mukai Takahito , Sakamoto Kensaku , Yokoyama Shigeyuki
Published: January 2019

Cell-free protein synthesis is useful for synthesizing difficult targets. The site-specific incorporation of non-natural amino acids into proteins is a powerful protein engineering method. In this study, we optimized the protocol for cell extract preparation from the Escherichia coli strain RFzero-iy, which is engineered to lack release factor 1 (RF-1). The BL21(DE3)-based RFzero-iy strain exhibited quite high cell-free protein productivity, and thus we established the protocols for its cell culture and extract preparation. In the presence of 3-iodo-l-tyrosine (IY), cell-free protein synthesis using the RFzero-iy-based S30 extract translated the UAG codon to IY at various sites with a high translation efficiency of >90%. In the absence of IY, the RFzero-iy-based cell-free system did not translate UAG to any amino acid, leaving UAG unassigned. Actually, UAG was readily reassigned to various non-natural amino acids, by supplementing them with their specific aminoacyl-tRNA synthetase variants (and their specific tRNAs) into the system. The high incorporation rate of our RFzero-iy-based cell-free system enables the incorporation of a variety of non-natural amino acids into multiple sites of proteins. The present strategy to create the RFzero strain is rapid, and thus promising for RF-1 deletions of various E. coli strains genomically engineered for specific requirements.
The Selective Acetamidine-Based iNOS Inhibitor CM544 Reduces Glioma Cell Proliferation by Enhancing PARP-1 Cleavage In Vitro
Authors: Gallorini Marialucia , Maccallini Cristina , Ammazzalorso Alessandra , Amoia Pasquale , De Filippis Barbara , Fantacuzzi Marialuigia , Giampietro Letizia , Cataldi Amelia , Amoroso Rosa
Published: January 2019

Gliomas are the most aggressive adult primary brain tumors. Expression of inducible Nitric Oxide Synthase has been reported as a hallmark of chemoresistance in gliomas and several studies have reported that inhibition of inducible Nitric Oxide Synthase could be related to a decreased proliferation of glioma cells. The present work was to analyze the molecular effects of the acetamidine derivative compound 39 (formally CM544, N-(3-{[(1-iminioethyl)amino]methyl}benzyl) prolinamide dihydrochloride), a newly synthetized iNOS inhibitor, in a C6 rat glioma cell model. There is evidence of CM544 selective binding to the iNOS, an event that triggers the accumulation of ROS/RNS, the expression of Nrf-2 and the phosphorylation of MAPKs after 3 h of treatment. In the long run, CM544 leads to the dephosphorylation of p38 and to a massive cleavage of PARP-1, confirming the block of C6 rat glioma cell proliferation in the G1/S checkpoint and the occurrence of necrotic cell death.
Discovery of New Cyclopentaquinoline Analogues as Multifunctional Agents for the Treatment of Alzheimer’s Disease
Authors: Czarnecka Kamila , Girek Małgorzata , Kręcisz Paweł , Skibiński Robert , Łątka Kamil , Jończyk Jakub , Bajda Marek , Kabziński Jacek , Majsterek Ireneusz , Szymczyk Piotr , Szymański Paweł
Published: January 2019

Here we report the two-step synthesis of 8 new cyclopentaquinoline derivatives as modifications of the tetrahydroacridine structure. Next, the biological assessment of each of them was performed. Based on the obtained results we identified 6-chloro-N-[2-(2,3-dihydro-1H-cyclopenta[b]quinolin-9-ylamino)-hexyl]]-nicotinamide hydrochloride (3e) as the most promising compound with inhibitory potencies against EeAChE and EqBuChE in the low nanomolar level 67 and 153 nM, respectively. Moreover, 3e compound is non-hepatotoxic, able to inhibit amyloid beta aggregation, and shows a mix-type of cholinesterase’s inhibition. The mixed type of inhibition of the compound was confirmed by molecular modeling. Then, yeast three-hybrid (Y3H) technology was used to confirm the known ligand-receptor interactions. New derivatives do not show antioxidant activity (confirmed by the use of two different tests). A pKa assay method was developed to identify the basic physicochemical properties of 3e compound. A LogP assay confirmed that 3e compound fulfills Lipinsky’s rule of five
Unacylated Ghrelin Improves Vascular Dysfunction and Attenuates Atherosclerosis during High-Fat Diet Consumption in Rodents
Authors: Zanetti Michela , Gortan Cappellari Gianluca , Graziani Andrea , Barazzoni Rocco
Published: January 2019

Unacylated ghrelin (UnGhr) exerts several beneficial actions on vascular function. The aim of this study was to assess the effects of UnGhr on high-fat induced endothelial dysfunction and its underlying mechanisms. Thoracic aortas from transgenic mice, which were overexpressing UnGhr and being control fed either a standard control diet (CD) or a high-fat diet (HFD) for 16 weeks, were harvested and used for the assessment of vascular reactivity, endothelial nitric oxide synthase (eNOS) expression and activity, thiobarbituric acid reactive substances (TBARS) and glutathione levels, and aortic lipid accumulation by Oil Red O staining. Relaxations due to acetylcholine and to DEA-NONOate were reduced (p < 0.05) in the HFD control aortas compared to vessels from the CD animals. Overexpression of UnGhr prevented HFD-induced vascular dysfunction, while eNOS expression and activity were similar in all vessels. HFD-induced vascular oxidative stress was demonstrated by increased (p < 0.05) aortic TBARS and glutathione in wild type (Wt) mice; however, this was not seen in UnGhr mice. Moreover, increased (p < 0.05) HFD-induced lipid accumulation in vessels from Wt mice was prevented by UnGhr overexpression. In conclusion, chronic UnGhr overexpression results in improved vascular function and reduced plaque formation through decreased vascular oxidative stress, without affecting the eNOS pathway. This research may provide new insight into the mechanisms underlying the beneficial effects of UnGhr on the vascular dysfunction associated with obesity and the metabolic syndrome.
The Interplay between Immunity and Microbiota at Intestinal Immunological Niche: The Case of Cancer
Authors: Cianci Rossella , Franza Laura , Schinzari Giovanni , Rossi Ernesto , Ianiro Gianluca , Tortora Giampaolo , Gasbarrini Antonio , Gambassi Giovanni , Cammarota Giovanni
Published: January 2019

The gut microbiota is central to the pathogenesis of several inflammatory and autoimmune diseases. While multiple mechanisms are involved, the immune system clearly plays a special role. Indeed, the breakdown of the physiological balance in gut microbial composition leads to dysbiosis, which is then able to enhance inflammation and to influence gene expression. At the same time, there is an intense cross-talk between the microbiota and the immunological niche in the intestinal mucosa. These interactions may pave the way to the development, growth and spreading of cancer, especially in the gastro-intestinal system. Here, we review the changes in microbiota composition, how they relate to the immunological imbalance, influencing the onset of different types of cancer and the impact of these mechanisms on the efficacy of traditional and upcoming cancer treatments.
Post-Injury Neuroprotective Effects of the Thalidomide Analog 3,6′-Dithiothalidomide on Traumatic Brain Injury
Authors: Batsaikhan Buyandelger , Wang Jing-Ya , Scerba Michael T. , Tweedie David , Greig Nigel H. , Miller Jonathan P. , Hoffer Barry J. , Lin Chih-Tung , Wang Jia-Yi
Published: January 2019

Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide. Long-term deficits after TBI arise not only from the direct effects of the injury but also from ongoing processes such as neuronal excitotoxicity, inflammation, oxidative stress and apoptosis. Tumor necrosis factor-α (TNF-α) is known to contribute to these processes. We have previously shown that 3,6′-dithiothalidomide (3,6′-DT), a thalidomide analog that is more potent than thalidomide with similar brain penetration, selectively inhibits the synthesis of TNF-α in cultured cells and reverses behavioral impairments induced by mild TBI in mice. In the present study, we further explored the therapeutic potential of 3,6′-DT in an animal model of moderate TBI using Sprague-Dawley rats subjected to controlled cortical impact. A single dose of 3,6′-DT (28 mg/kg, i.p.) at 5 h after TBI significantly reduced contusion volume, neuronal degeneration, neuronal apoptosis and neurological deficits at 24 h post-injury. Expression of pro-inflammatory cytokines in the contusion regions were also suppressed at the transcription and translation level by 3,6′-DT. Notably, neuronal oxidative stress was also suppressed by 3,6′-DT. We conclude that 3,6′-DT may represent a potential therapy to ameliorate TBI-induced functional deficits.