bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Number of Copies, Structure, Behavior and Copy Number Variations (CNV) of the Y Chromosome in Male Infertility
Authors: Signore Fabrizio , Gulìa Caterina , Votino Raffaella , De Leo Vincenzo , Zaami Simona , Putignani Lorenza , Gigli Silvia , Santini Edoardo , Bertacca Luca , Porrello Alessandro , Piergentili Roberto
Published: December 2019

The World Health Organization (WHO) defines infertility as the inability of a sexually active, non-contracepting couple to achieve spontaneous pregnancy within one year. Statistics show that the two sexes are equally at risk. Several causes may be responsible for male infertility; however, in 30–40% of cases a diagnosis of idiopathic male infertility is made in men with normal urogenital anatomy, no history of familial fertility-related diseases and a normal panel of values as for endocrine, genetic and biochemical markers. Idiopathic male infertility may be the result of gene/environment interactions, genetic and epigenetic abnormalities. Numerical and structural anomalies of the Y chromosome represent a minor yet significant proportion and are the topic discussed in this review. We searched the PubMed database and major search engines for reports about Y-linked male infertility. We present cases of Y-linked male infertility in terms of (i) anomalies of the Y chromosome structure/number; (ii) Y chromosome misbehavior in a normal genetic background; (iii) Y chromosome copy number variations (CNVs). We discuss possible explanations of male infertility caused by mutations, lower or higher number of copies of otherwise wild type, Y-linked sequences. Despite Y chromosome structural anomalies are not a major cause of male infertility, in case of negative results and of normal DNA sequencing of the ascertained genes causing infertility and mapping on this chromosome, we recommend an analysis of the karyotype integrity in all cases of idiopathic fertility impairment, with an emphasis on the structure and number of this chromosome.
Developmental Transcriptomic Analysis of the Cave-Dwelling Crustacean, Asellus aquaticus
Authors: Gross Joshua B. , Sun Dennis A. , Carlson Brian M. , Brodo-Abo Sivan , Protas Meredith E.
Published: December 2019

Cave animals are a fascinating group of species often demonstrating characteristics including reduced eyes and pigmentation, metabolic efficiency, and enhanced sensory systems. Asellus aquaticus, an isopod crustacean, is an emerging model for cave biology. Cave and surface forms of this species differ in many characteristics, including eye size, pigmentation, and antennal length. Existing resources for this species include a linkage map, mapped regions responsible for eye and pigmentation traits, sequenced adult transcriptomes, and comparative embryological descriptions of the surface and cave forms. Our ultimate goal is to identify genes and mutations responsible for the differences between the cave and surface forms. To advance this goal, we decided to use a transcriptomic approach. Because many of these changes first appear during embryonic development, we sequenced embryonic transcriptomes of cave, surface, and hybrid individuals at the stage when eyes and pigment become evident in the surface form. We generated a cave, a surface, a hybrid, and an integrated transcriptome to identify differentially expressed genes in the cave and surface forms. Additionally, we identified genes with allele-specific expression in hybrid individuals. These embryonic transcriptomes are an important resource to assist in our ultimate goal of determining the genetic underpinnings of the divergence between the cave and surface forms.
Examination of the Responsiveness of the Great Recess Framework—Observational Tool
Authors: Massey William V. , Stellino Megan B. , Hayden Laura , Thalken Janelle
Published: December 2019

The purpose of this study was to test the responsiveness of the great recess framework-observational tool (GRF-OT) to detect changes in recess quality. GRF-OT data were collected at two time points (fall 2017 and spring 2018) in four geographically distinct regions of the United States. Following recommendations by Massey et al. (2018), a three-day average of recess observations was used for each data point. Data analysis was conducted on nine schools contracted to receive services from Playworks, a national non-profit organization specializing in recess implementation, for the first time; eight schools with returning Playworks services (i.e., multiple years of service) and five schools with no intervention services. Analysis of the change in GRF-OT scores from fall to spring revealed a large effect for first-year intervention schools (g = 1.19; 95% CI 0.13, 2.25) and multi-year intervention schools (g = 0.788; 95% CI −0.204, 1.78). GRF-OT scores decreased for schools not receiving an intervention (g = −0.562; 95% CI, −2.20, 1.07). New intervention schools (odds ratio= 21.59; 95% CI 4.27, 109.15) and multi-year intervention schools (odds ratio= 7.34; 95% CI 1.50, 35.97) were more likely to meet the threshold for meaningful positive change than non-intervention schools. The results of the current study suggest that GRF-OT is a responsive tool that researchers, practitioners, and policy makers can use to measure and assess changes in the quality of the recess environment.
Predominant Mechanisms in the Treatment of Wastewater Due to Interaction of Benzaldehyde and Iron Slag Byproduct
Authors: Faisal Ayad A. H. , Alquzweeni Saif S. , Naji Laith A. , Naushad Mu
Published: December 2019

Iron slag is a byproduct generated in huge quantities from recycled remnants of iron and steel factories; therefore, the possibility of using this waste in the removal of benzaldehyde from contaminated water offers an excellent topic in sustainability field. Results reveal that the removal efficiency was equal to 85% for the interaction of slag and water contaminated with benzaldehyde at the best operational conditions of 0.3 g/100 mL, 6, 180 min, and 250 rpm for the sorbent dosage, initial pH, agitation time, and speed, respectively with 300 mg/L initial concentration. The maximum uptake capacity of iron slag was 118.25 mg/g which was calculated by the Langmuir model. Physical sorption may be the major mechanism for the removal of benzaldehyde onto iron slag based on the analysis of isotherm and kinetic sorption data and thermodynamically, the process was spontaneous and endothermic. Finally, the X-ray fluorescence spectroscopy (XRF), X-ray diffraction (XRD), Fourier transform infrared (FT-IR), scanning electron microscope (SEM) and energy-dispersive spectroscope (EDS) tests for reactive material certified that the dissolution of calcium oxide can enhance the removal of benzaldehyde by the formation of bridge cations.
Health and Work Environment among Female and Male Swedish Elementary School Teachers—A Cross-Sectional Study
Authors: Boström Maria , Björklund Christina , Bergström Gunnar , Nybergh Lotta , Schäfer Elinder Liselotte , Stigmar Kjerstin , Wåhlin Charlotte , Jensen Irene , Kwak Lydia
Published: December 2019

Background and objectives: Changes in teachers’ work situation in Sweden since the 1990s may have contributed to an increase in common mental disorders (CMDs) and burnout. However, there is a lack of research in this field. The aim was to describe how Swedish elementary school teachers experience their health, organizational and social work environment, and the psychosocial safety climate at the workplace, and especially differences and similarities between female and male teachers. Materials and methods: Data were collected with the COPSOQ, OLBI, UWES and PSC-12 from 478 elementary teachers, 81.0% of them women, from twenty schools. The response rate was 96.4%. Results: Teachers reported relatively good general health but experienced high stress, high work pace and emotional demands, low influence at work and a poor psychosocial safety climate. These factors were especially prominent among female teachers. Both women and men experienced good development possibilities and high work engagement. Conclusions: The results of this study can help us to develop a more sustainable work environment for female and male teachers. A more sustainable work environment might attract more people to the profession and incentivize existing teachers to remain in the profession.
Association of Anxiety over Radiation Exposure and Acquisition of Knowledge Regarding Occupational Health Management in Operation Leader Candidates of Radioactivity Decontamination Workers in Fukushima, Japan: A Cross-Sectional Study
Authors: Hidaka Tomoo , Kakamu Takeyasu , Endo Shota , Kasuga Hideaki , Masuishi Yusuke , Kumagai Tomohiro , Sato Sei , Sasaki Takuma , Fukushima Tetsuhito
Published: December 2019

An operation leader (OL) of radioactivity decontamination workers is required by law to have accurate knowledge of occupational health management (OHM) such as working environment management, control of operations, and health management as a field supervisor in Japan. The purpose of the current study is to examine the association between anxiety over radiation exposure and the possession/acquisition of the OHM knowledge required for OLs. In this cross-sectional study, data were collected before and after training sessions held by Fukushima Prefecture Labor Standard Associations in Fukushima, Japan, in 2017. Eighty-seven males who completed the questionnaires were enrolled to this study. As a result, acquisition of knowledge of working environment management was significantly associated with an increase of anxiety over radiation exposure after the session comparing the situation before and after the session (knowledge possession; odds ratio = 4.489; 95% confidence interval = 1.216, 16.571). In conclusion, acquisition of accurate knowledge of how to manage working environment management was associated with anxiety over radiation exposure. Although acquisition of said knowledge may contribute to the reduction of physical health risks, it may increase mental health risks. Both mental health support for OLs with accurate knowledge and educational support for those without accurate knowledge are required.
Spatiotemporal Variations and Factors of Air Quality in Urban Central China during 2013–2015
Authors: Mao Mao , Zhang Xiaolin , Shao Yamei , Yin Yan
Published: December 2019

Spatiotemporal behaviors of particulate matter (PM2.5 and PM10) and trace gases (SO2, NO2, CO, and O3) in Hefei during the period from December 2013 to November 2015 are investigated. The mean annual PM2.5 (PM10) concentrations are 89.1 ± 59.4 µg/m3 (118.9 ± 66.8 µg/m3) and 61.6 ± 32.2 µg/m3 (91.3 ± 40.9 µg/m3) during 2014 and 2015, respectively, remarkably exceeding the Chinese Ambient Air Quality Standards (CAAQS) grade II. All trace gases basically meet the requirements though NO2 and O3 have a certain upward trend. Old districts have the highest pollution levels, followed by urban periphery sites and new districts. Severe haze pollution occurs in Hefei, with frequent exceedances in particulate matter with 178 (91) days in 2014 (2015). The abnormal PM2.5 concentrations in June 2014 attributed to agricultural biomass burning from moderate resolution imaging spectroradiometry (MODIS) wildfire maps and aerosol optical depth (AOD) analysis. PM2.5 is recognized as the major pollutant, and a longer interspecies relationship is found between PM2.5 and other criteria pollutants for episode days as compared to non-episode days. The air pollution in Hefei tends to be influenced by local primary emissions, secondary formation, and regional transport from adjacent cities and remote regions. Most areas of Anhui, southern Jiangsu, northern Zhejiang, and western Shandong are identified as the common high-potential source regions of PM2.5. Approximately 9.44 and 8.53 thousand premature mortalities are attributed to PM2.5 exposure in 2014 and 2015. The mortality benefits will be 32% (24%), 47% (41%), 70% (67%), and 85% (83%) of the total premature mortalities in 2014 (2015) when PM2.5 concentrations meet the CAAQS grade II, the World Health Organization (WHO) IT-2, IT-3, and Air Quality Guideline, respectively. Hence, joint pollution prevention and control measures need to be strengthened due to pollutant regional diffusion, and much higher health benefits could be achieved as the Hefei government adopts more stringent WHO guidelines for PM2.5.
A Technological Scenario for a Healthier, More Equitable and Sustainable Europe in 2040: Citizen Perceptions and Policy Implications
Authors: Xhelili Arlind , Strube Rosa , Grossi Francesca , Zvěřinová Iva , Taylor Timothy , Martinez-Juarez Pablo , Quiroga Sonia , Suárez Cristina , Gjorgjev Dragan
Published: December 2019

This article aims at exploring, understanding and comparing European citizens’ insights and perceptions towards “My life between realities”, a positive future scenario which depicts a narrative of reaching healthier, more equitable and sustainable societies by 2040 with the support of technology and technological solutions. It responds to the need for gathering and incorporating more citizen insights into future policy developments and strategic actions to tackle the global challenge of unsustainable development. Citizens of five European countries—the Czech Republic, Germany, North Macedonia, Spain and the United Kingdom—have been consulted through focus groups. The exercise has uncovered citizens’ preferences and attitudes towards four main lifestyle areas; namely, green spaces, energy efficient housing, active mobility and (food) consumption. The technological attributes of the scenario led to citizens expressing diametrically opposed and critical perceptions and attitudes. Given the prospects of technology in driving sustainable development, based on these insights, policy recommendations for the better integration and acceptance of technological advances by the public are discussed herein.
Toxicity Evaluation of Quantum Dots (ZnS and CdS) Singly and Combined in Zebrafish (Danio rerio)
Authors: Matos Beatriz , Martins Marta , Samamed Antonio Cid , Sousa David , Ferreira Isabel , Diniz Mário S.
Published: December 2019

The exponential growth of nanotechnology has led to the production of large quantities of nanomaterials for numerous industrial, technological, agricultural, environmental, food and many other applications. However, this huge production has raised growing concerns about the adverse effects that the release of these nanomaterials may have on the environment and on living organisms. Regarding the effects of QDs on aquatic organisms, existing data is scarce and often contradictory. Thus, more information is needed to understand the mechanisms associated with the potential toxicity of these nanomaterials in the aquatic environment. The toxicity of QDs (ZnS and CdS) was evaluated in the freshwater fish Danio rerio. The fishes were exposed for seven days to different concentrations of QDs (10, 100 and 1000 µg/L) individually and combined. Oxidative stress enzymes (catalase, superoxide dismutase and glutathione S-transferase), lipid peroxidation, HSP70 and total ubiquitin were assessed. In general, results suggest low to moderate toxicity as shown by the increase in catalase activity and lipid peroxidation levels. The QDs (ZnS and CdS) appear to cause more adverse effects singly than when tested combined. However, LPO results suggest that exposure to CdS singly caused more oxidative stress in zebrafish than ZnS or when the two QDs were tested combined. Levels of Zn and Cd measured in fish tissues indicate that both elements were bioaccumulated by fish and the concentrations increased in tissues according to the concentrations tested. The increase in HSP70 measured in fish exposed to 100 µg ZnS-QDs/L may be associated with high levels of Zn determined in fish tissues. No significant changes were detected for total ubiquitin. More experiments should be performed to fully understand the effects of QDs exposure to aquatic biota.
The Effect of Respiratory Muscle Training on the Pulmonary Function, Lung Ventilation, and Endurance Performance of Young Soccer Players
Authors: Mackała Krzysztof , Kurzaj Monika , Okrzymowska Paulina , Stodółka Jacek , Coh Milan , Rożek-Piechura Krystyna
Published: December 2019

This study investigated whether the addition of eight weeks of inspiratory muscle training (IMT) to a regular preseason soccer training program, including incremental endurance training (IET), would change pulmonary function, lung ventilation, and aerobic performance in young soccer players. Sixteen club-level competitive junior soccer players (mean age 17.63 ± 0.48 years, height 182 ± 0.05 cm, body mass 68.88 ± 4.48 kg) participated in the study. Participants were randomly assigned into two groups: experimental (n = 8) and control (n = 8). Both groups performed regular preseason soccer training, including endurance workouts as IET. In addition to this training, the experimental group performed additional IMT for eigght weeks with a commercially available respiratory muscle trainer (Threshold IMT), with a total of 80 inhalations (twice per day, five days per week). Pre- and post-intervention tests of pulmonary function, maximal inspiratory pressure, and the Cooper test were implemented. Eight weeks of IMT had a positive impact on expiratory muscle strength (p = 0.001); however, there was no significant effect on respiratory function parameters. The results also indicate increased efficiency of the inspiratory muscles, contributing to an improvement in aerobic endurance, measured by VO₂max estimated from running distance in the cardiorespiratory Cooper test (p < 0.005).
Sedentariness of College Students Is Negatively Associated with Perceived Neighborhood Greenness at Home, but Not at University
Authors: Loder Alexander Karl Ferdinand , van Poppel Mireille Nicoline Maria
Published: December 2019

Previous studies reported contradictory evidence for associations between perceived greenness and obesity mediated by physical activity, focusing on people’s homes or general greenness. Data are lacking in other environments. We studied the association of perceived greenness at home and at university with BMI and physical activity. An online survey collected data from 601 participants, living and studying in and around the city of Graz, Austria; mean age of 24 years. Greenness was assessed using questions on quality of and access to green space; Body mass index (BMI) was derived from self-reported measures; physical activity and sedentariness were measured using the IPAQ questionnaire (short version). On average, BMI was 22.6 (SD = 3.7), physical activity was 63.3 (SD = 51.7) METh/week, and participants spent 5.8 (SD = 4.0) h/day sitting. Regression analyses revealed no associations between perceived greenness and BMI and physical activity for all environments, but a negative association for sedentariness and perceived greenness at home, but not at university. The results indicate a relation between perceived greenness and sedentariness, which differs for the home-and study environment.
Exploring the Associations of Walking Behavior with Neighborhood Environments by Different Life Stages: A Cross-Sectional Study in a Smaller Chinese City
Authors: Sun Ziwen , Lai Ka Yan , Bell Simon , Scott Iain , Zhang Xiaomeng
Published: December 2019

Because of high population density and rapid urbanization, different human life stages have distinct growth experiences, leading to different lifestyles and age-spatial separation in the same neighborhood environment, particularly in smaller Chinese cities. The relationship of environment to physical activity may differ from western or larger Chinese cities. This study examined the associations of walking duration to the neighborhood environment and other factors, and explored the nuances of walking behavior for different life stages of adults in a smaller Chinese city, Yuncheng. An interviewer-administered questionnaire survey (n = 173) and face-to-face interviews (n = 19) were conducted in August 2017. Descriptive analysis and multiple linear regression were performed to describe walking motivations, sociodemographic characteristics, neighborhood environments, and their impacts on walking duration across three life stages. The quantitative findings were followed by interviews to validate and interpret them. Our results showed no positive associations of land-use mix (LUM) and residential density on walking duration, and even inverse associations of LUM-recreation and LUM-education for specific life stages were identified. Younger people’s walking behavior was more related to consumption amenities distinct from those of older people. Our findings suggest that using walkable neighborhood policies (e.g., high residential density and land-use mix) to increase physical activity might be ineffective in smaller Chinese cities.
Should We Scale-Up? A Mixed Methods Process Evaluation of an Intervention Targeting Sedentary Office Workers Using the RE-AIM QuEST Framework
Authors: MacDonald Bradley , Gibson Ann-Marie , Janssen Xanne , Hutchinson Jasmin , Headley Samuel , Matthews Tracey , Kirk Alison
Published: December 2019

Background: Interventions targeting a reduction in sedentary behaviour in office workers need to be scaled-up to have impact. In this study, the RE-AIM QuEST framework was used to evaluate the potential for further implementation and scale-up of a consultation based workplace intervention which targeted both the reduction, and breaking up of sitting time. Methods: To evaluate the Springfield College sedentary behaviour intervention across multiple RE-AIM QuEST indicators; intervention participant, non-participant (employees who did not participate) and key informant (consultation delivery team; members of the research team and stakeholders in workplace health promotion) data were collected using interviews, focus groups and questionnaires. Questionnaires were summarized using descriptive statistics and interviews and focus groups were transcribed verbatim, and thematically analysed. Results: Barriers to scale-up were: participant burden of activity monitoring; lack of management support; influence of policy; flexibility (scheduling/locations); time and cost. Facilitators to scale up were: visible leadership; social and cultural changes in the workplace; high acceptability; existing health and wellbeing programmes; culture and philosophy of the participating college. Conclusions: There is potential for scale-up, however adaptations will need to be made to address the barriers to scale-up. Future interventions in office workers should evaluate for scalability during the pilot phases of research.
The Perceived Availability of Online Social Support: Exploring the Contributions of Illness and Rural Identities in Adults with Chronic Respiratory Illness
Authors: Paige Samantha R. , Damiani Rachel E. , Flood-Grady Elizabeth , Krieger Janice L. , Stellefson Michael
Published: December 2019

Joining an online social support group may increase perceived membership to a community, but it does not guarantee that the community will be available when it is needed. This is especially relevant for adults with Chronic Obstructive Pulmonary Disease (COPD), many of whom reside in rural regions and continually negotiate their illness identity. Drawing from social support literature and communication theory of identity, this cross-sectional study explored how COPD illness and geographic identities interact to influence patients’ perceived availability of online social support. In April 2018, 575 adults with a history of respiratory symptoms completed an online survey. Patients with a COPD diagnosis reported greater availability of online support. This was partially mediated by a positive degree of COPD illness identity (i.e., being diagnosed with COPD, a history of tobacco use, severe respiratory symptoms, high disease knowledge, and low income but high education). The relationship between COPD illness identity and the availability of online support was strongest among those with low rural identity; however, at lower levels of COPD illness identity, participants with high rural identity reported the greatest degree of available online support. Results have important implications for tailored education approaches across the COPD care continuum by illness and geographic identities.
Consumers’ Willingness to Pay for Imported Milk: Based on Shanghai, China
Authors: Xu Lingling , Yang Xixi , Wu Linhai
Published: December 2019

Against the backdrop of the continuous large-scale growth of imported milk in China, in this research 310 consumers in Shanghai were used as a sample, and a choice experiment was conducted to study consumer preference and willingness to pay for imported milk. The following product attributes were included: nutrition claim, fat content, flavor, country of origin, and price. Our results show that, excepting price, consumers consider flavor the most important attribute, followed by nutrition claim, fat content, and country of origin. Consumers can be delineated into four segments based on consumer preference for the attributes of imported milk: “nutrition claim seekers” are willing to pay the highest price for imported milk with nutrition claims, “indifferent” consumers pay little attention to imported milk attributes, “flavor-oriented” consumers have a strong preference for strawberry-flavored imported milk, and “price-sensitive” consumers weigh the price when choosing imported milk.
Effect of Work Environment on Presenteeism among Aging American Workers: The Moderated Mediating Effect of Sense of Control
Authors: Yang Tianan , Shi Hubin , Guo Yuangeng , Jin Xuan , Liu Yexin , Gao Yongchuang , Deng Jianwei
Published: December 2019

With the rapid increase of aging workforces, companies worldwide are concerned with improving the health and working status of older workers. Sense of control is an important psychological variable in sociology but has attracted less attention in studies of occupational health and management. This study examined the association of sense of control with presenteeism among aging workers in the United States. Data from the Health and Retirement Survey were analyzed, specifically, 2308 observations in 2012. Structural equation modeling was used to assess work environment, sense of control (measured in relation to personal mastery and perceived constraints), and associations with presenteeism. The moderating effect of subjective social status on the association between sense of control and presenteeism was examined with a moderated mediation model. In the final structural equation modeling model, work environment was directly inversely associated with presenteeism, and work environment was significantly inversely associated with perceived constraints. There was a direct positive association between work environment and personal mastery, a direct positive association between perceived constraints and presenteeism, and a significant inverse association between personal mastery and presenteeism. The significant indirect effects between work environment and presenteeism were significantly mediated by sense of control. Subjective social status inversely moderated the relation between presenteeism and perceived mastery, a dimension of sense of control. To increase the performance of aging workers in the United States, managers should create a work environment that facilitates access to job resources, as this might improve personal sense of control, particularly among those with high subjective social status.
Assessing and Improving the Quality in Mental Health Services
Authors: Samartzis Lampros , Talias Michael A.
Published: December 2019

Background: The mental health of the population consists of the three essential pillars of quality of life, economy, and society. Mental health services take care of the prevention and treatment of mental disorders and through them maintain, improve, and restore the mental health of the population. The purpose of this study is to describe the methodology for qualitative and quantitative evaluation and improvement of the mental health service system. Methods: This is a narrative review study that searches the literature to provide criteria, indicators, and methodology for evaluating and improving the quality of mental health services and the related qualitative and quantitative indicators. The bibliography was searched in popular databases PubMed, Google Scholar, CINAHL, using the keywords “mental”, “health”, “quality”, “indicators”, alone or in combinations thereof. Results: Important quality indicators of mental health services have been collected and presented, and modified where appropriate. The definition of each indicator is presented here, alongside its method of calculation and importance. Each indicator belongs to one of the eight dimensions of quality assessment: (1) Suitability of services, (2) Accessibility of patients to services, (3) Acceptance of services by patients, (4) Ability of healthcare professionals to provide services, (5) Efficiency of health professionals and providers, (6) Continuity of service over time (ensuring therapeutic continuity), (7) Efficiency of health professionals and services, (8) Safety (for patients and for health professionals). Discussion/Conclusions: Accessibility and acceptability of service indicators are important for the attractiveness of services related to their use by the population. Profitability indicators are important economic indicators that affect the viability and sustainability of services, factors that are now taken into account in any health policy. All of the indicators mentioned are related to public health, affecting the quality of life, morbidity, mortality, and life expectancy, directly or indirectly. The systematic measurement and monitoring of indicators and the measurement and quantification of quality through them, are the basis for evidence-based health policy for improvement of the quality of mental health services.
Evolving a Peptide: Library Platforms and Diversification Strategies
Authors: Bozovičar Krištof , Bratkovič Tomaž
Published: December 2019

Peptides are widely used in pharmaceutical industry as active pharmaceutical ingredients, versatile tools in drug discovery, and for drug delivery. They find themselves at the crossroads of small molecules and proteins, possessing favorable tissue penetration and the capability to engage into specific and high-affinity interactions with endogenous receptors. One of the commonly employed approaches in peptide discovery and design is to screen combinatorial libraries, comprising a myriad of peptide variants of either chemical or biological origin. In this review, we focus mainly on recombinant peptide libraries, discussing different platforms for their display or expression, and various diversification strategies for library design. We take a look at well-established technologies as well as new developments and future directions.
Alpha-Tocotrienol Prevents Oxidative Stress-Mediated Post-Translational Cleavage of Bcl-xL in Primary Hippocampal Neurons
Authors: Park Han-A , Mnatsakanyan Nelli , Broman Katheryn , Davis Abigail U. , May Jordan , Licznerski Pawel , Crowe-White Kristi M. , Lackey Kimberly H. , Jonas Elizabeth A.
Published: December 2019

B-cell lymphoma-extra large (Bcl-xL) is an anti-apoptotic member of the Bcl2 family of proteins, which supports neurite outgrowth and neurotransmission by improving mitochondrial function. During excitotoxic stimulation, however, Bcl-xL undergoes post-translational cleavage to ∆N-Bcl-xL, and accumulation of ∆N-Bcl-xL causes mitochondrial dysfunction and neuronal death. In this study, we hypothesized that the generation of reactive oxygen species (ROS) during excitotoxicity leads to formation of ∆N-Bcl-xL. We further proposed that the application of an antioxidant with neuroprotective properties such as α-tocotrienol (TCT) will prevent ∆N-Bcl-xL-induced mitochondrial dysfunction via its antioxidant properties. Primary hippocampal neurons were treated with α-TCT, glutamate, or a combination of both. Glutamate challenge significantly increased cytosolic and mitochondrial ROS and ∆N-Bcl-xL levels. ∆N-Bcl-xL accumulation was accompanied by intracellular ATP depletion, loss of mitochondrial membrane potential, and cell death. α-TCT prevented loss of mitochondrial membrane potential in hippocampal neurons overexpressing ∆N-Bcl-xL, suggesting that ∆N-Bcl-xL caused the loss of mitochondrial function under excitotoxic conditions. Our data suggest that production of ROS is an important cause of ∆N-Bcl-xL formation and that preventing ROS production may be an effective strategy to prevent ∆N-Bcl-xL-mediated mitochondrial dysfunction and thus promote neuronal survival.
Claudins in the Renal Collecting Duct
Authors: Leiz Janna , Schmidt-Ott Kai M.
Published: December 2019

The renal collecting duct fine-tunes urinary composition, and thereby, coordinates key physiological processes, such as volume/blood pressure regulation, electrolyte-free water reabsorption, and acid-base homeostasis. The collecting duct epithelium is comprised of a tight epithelial barrier resulting in a strict separation of intraluminal urine and the interstitium. Tight junctions are key players in enforcing this barrier and in regulating paracellular transport of solutes across the epithelium. The features of tight junctions across different epithelia are strongly determined by their molecular composition. Claudins are particularly important structural components of tight junctions because they confer barrier and transport properties. In the collecting duct, a specific set of claudins (Cldn-3, Cldn-4, Cldn-7, Cldn-8) is expressed, and each of these claudins has been implicated in mediating aspects of the specific properties of its tight junction. The functional disruption of individual claudins or of the overall barrier function results in defects of blood pressure and water homeostasis. In this concise review, we provide an overview of the current knowledge on the role of the collecting duct epithelial barrier and of claudins in collecting duct function and pathophysiology.
Composing the Early Embryonic Microenvironment: Physiology and Regulation of Oviductal Secretions
Authors: Saint-Dizier Marie , Schoen Jennifer , Chen Shuai , Banliat Charles , Mermillod Pascal
Published: December 2019

The oviductal fluid is the first environment experienced by mammalian embryos at the very beginning of life. However, it has long been believed that the oviductal environment was not essential for proper embryonic development. Successful establishment of in vitro embryo production techniques (which completely bypass the oviduct) have reinforced this idea. Yet, it became evident that in vitro produced embryos differ markedly from their in vivo counterparts, and these differences are associated with lower pregnancy outcomes and more health issues after birth. Nowadays, researchers consider the oviduct as the most suitable microenvironment for early embryonic development and a substantial effort is made to understand its dynamic, species-specific functions. In this review, we touch on the origin and molecular components of the oviductal fluid in mammals, where recent progress has been made thanks to the wider use of mass spectrometry techniques. Some of the factors and processes known to regulate oviductal secretions, including the embryo itself, as well as ovulation, insemination, endogenous and exogenous hormones, and metabolic and heat stress, are summarized. Special emphasis is laid on farm animals because, owing to the availability of sample material and the economic importance of fertility in livestock husbandry, a large part of the work on this topic has been carried out in domestic animals used for dairy and/or meat production.
HP-CagA+ Regulates the Expression of CDK4/CyclinD1 via reg3 to Change Cell Cycle and Promote Cell Proliferation
Authors: Liu Bin , Li Xiaokang , Sun Fuze , Tong Xiaoling , Bai Yanmin , Jin Kairang , Liu Lin , Dai Fangyin , Li Niannian
Published: December 2019

Previous studies have shown that regeneration gene 3 (reg3) is significantly expressed in gastric mucosa tissues with Helicobacter pylori (HP) cytotoxin-associated gene A (CagA)-positive (HP-CagA+). CagA-positive HP increases the risk of gastric cancer. The purpose of this study was to investigate the correlation between reg3 and HP-CagA+ and explore the effects of reg3 on the proliferation of gastric cancer cells and the development of tissues and organs. We analyzed the expression of reg3 in human tissues and organs. The results showed that reg3 expression in gastric tissues was significantly higher than that in other tissues and organs. In addition, reg3 influenced the prognosis of gastric, lung, and ovarian cancers. Immunohistochemical analysis indicated that the expression of reg3 and CagA in cancerous tissues was higher than that in adjacent tissues. HP-CagA+ infection of gastric cancer cells promotes reg3 expression, suggesting that reg3 may be a target gene of CagA in gastric cancer, which together affects the formation and development of gastric cancer. reg3 and CagA promote cell proliferation, and then affect the development of mouse tissues and organs by regulating G1/S phase transition of the cell cycle via the formation of the cell cycle-dependent complex CDK4/CyclinD1. This is the first study that shows the influence of CagA on the cell cycle and induction of cell proliferation by promoting reg3 expression.
Particulate Matter Increases the Severity of Bleomycin-Induced Pulmonary Fibrosis through KC-Mediated Neutrophil Chemotaxis
Authors: Cheng I-Yin , Liu Chen-Chi , Lin Jiun-Han , Hsu Tien-Wei , Hsu Jyuan-Wei , Li Anna Fen-Yau , Ho Wen-Chao , Hung Shih-Chieh , Hsu Han-Shui
Published: December 2019

Background: Although particular matter (PM) increases incidence and severity of idiopathic pulmonary fibrosis, the underlying mechanism remains elusive. Methods: The effects of PM were evaluated in a murine model of bleomycin-induced pulmonary fibrosis. Mice were divided into four groups, receiving: (1) Saline (control), (2) bleomycin, (3) PM, or (4) bleomycin plus PM (Bleo+PM). Additional groups of Bleo+PM mice were treated with sivelestat (an inhibitor of neutrophil elastase) or reparixin (a C-X-C motif chemokine receptor 2 antagonist), or were genetically modified with keratinocyte chemoattractant (KC) deletion. Results: Pulmonary fibrosis was not observed in the control or PM groups. Bleomycin induced pulmonary fibrosis within 14 days. The Bleo+PM group showed worse pulmonary fibrosis when compared to the bleomycin group. Analyses of immune cell profile and chemokine/cytokine concentrations at day 2-bronchoalveolar lavage fluid (BALF) revealed that the Bleo+PM group had increased neutrophil number and elastase level and KC concentration compared to the bleomycin group. Neutrophil elastase activated the Smad2/Smad3/α-SMA pathway to induce collagen deposition, while sivelestat abrogated the increased severity of pulmonary fibrosis caused by PM. Chemotaxis assay revealed that BALF of the Bleo+PM group recruited neutrophil, which was dependent on KC. Further, genetic KC deletion or pharmaceutical inhibition of KC binding to CXCR2 with reparixin ameliorated the PM-induced increased severity of pulmonary fibrosis. Conclusions: These data provide evidence that the PM-induced increased severity of pulmonary fibrosis depends on KC-mediated neutrophil chemotaxis and give additional mechanic insight that will aid in the development of therapeutic strategies.
Molecular and Cellular Risk Assessment of Healthy Human Cells and Cancer Human Cells Exposed to Nanoparticles
Authors: Helal-Neto Edward , de Barros Aline Oliveira da Silva , Saldanha-Gama Roberta , Brandão-Costa Renata , Alencar Luciana Magalhães Rebêlo , dos Santos Clenilton Costa , Martínez-Máñez Ramón , Ricci-Junior Eduardo , Alexis Frank , Morandi Verônica , Barja-Fidalgo Christina , Santos-Oliveira Ralph
Published: December 2019

Nanodrugs have in recent years been a subject of great debate. In 2017 alone, almost 50 nanodrugs were approved for clinical use worldwide. Despite the advantages related to nanodrugs/nanomedicine, there is still a lack of information regarding the biological safety, as the real behavior of these nanodrugs in the body. In order to better understand these aspects, in this study, we evaluated the effect of polylactic acid (PLA) nanoparticles (NPs) and magnetic core mesoporous silica nanoparticles (MMSN), of 1000 nm and 50 nm, respectively, on human cells. In this direction we evaluated the cell cycle, cytochemistry, proliferation and tubulogenesis on tumor cells lines: from melanoma (MV3), breast cancer (MCF-7, MDA-MB-213), glioma (U373MG), prostate (PC3), gastric (AGS) and colon adenocarcinoma (HT-29) and non-tumor cell lines: from human melanocyte (NGM), fibroblast (FGH) and endothelial (HUVEC), respectively. The data showed that an acute exposure to both, polymeric nanoparticles or MMSN, did not show any relevant toxic effects on neither tumor cells nor non-tumor cells, suggesting that although nanodrugs may present unrevealed aspects, under acute exposition to human cells they are harmless.
2-Deoxy-d-Glucose and Its Analogs: From Diagnostic to Therapeutic Agents
Authors: Pajak B. , Siwiak E. , Sołtyka M. , Priebe A. , Zieliński R. , Fokt I. , Ziemniak M. , Jaśkiewicz A. , Borowski R. , Domoradzki T. , Priebe W.
Published: December 2019

The ability of 2-deoxy-d-glucose (2-DG) to interfere with d-glucose metabolism demonstrates that nutrient and energy deprivation is an efficient tool to suppress cancer cell growth and survival. Acting as a d-glucose mimic, 2-DG inhibits glycolysis due to formation and intracellular accumulation of 2-deoxy-d-glucose-6-phosphate (2-DG6P), inhibiting the function of hexokinase and glucose-6-phosphate isomerase, and inducing cell death. In addition to glycolysis inhibition, other molecular processes are also affected by 2-DG. Attempts to improve 2-DG’s drug-like properties, its role as a potential adjuvant for other chemotherapeutics, and novel 2-DG analogs as promising new anticancer agents are discussed in this review.
Establishment and Characterization of a Murine Mucosal Mast Cell Culture Model
Authors: Kakinoki Aya , Kameo Tsuyoshi , Yamashita Shoko , Furuta Kazuyuki , Tanaka Satoshi
Published: December 2019

Accumulating evidence suggests that mast cells play critical roles in disruption and maintenance of intestinal homeostasis, although it remains unknown how they affect the local microenvironment. Interleukin-9 (IL-9) was found to play critical roles in intestinal mast cell accumulation induced in various pathological conditions, such as parasite infection and oral allergen-induced anaphylaxis. Newly recruited intestinal mast cells trigger inflammatory responses and damage epithelial integrity through release of a wide variety of mediators including mast cell proteases. We established a novel culture model (IL-9-modified mast cells, MCs/IL-9), in which murine IL-3-dependent bone-marrow-derived cultured mast cells (BMMCs) were further cultured in the presence of stem cell factor and IL-9. In MCs/IL-9, drastic upregulation of Mcpt1 and Mcpt2 was found. Although histamine storage and tryptase activity were significantly downregulated in the presence of SCF and IL-9, this was entirely reversed when mast cells were cocultured with a murine fibroblastic cell line, Swiss 3T3. MCs/IL-9 underwent degranulation upon IgE-mediated antigen stimulation, which was found to less sensitive to lower concentrations of IgE in comparison with BMMCs. This model might be useful for investigation of the spatiotemporal changes of newly recruited intestinal mast cells.
Targeting XPO1 and PAK4 in 8505C Anaplastic Thyroid Cancer Cells: Putative Implications for Overcoming Lenvatinib Therapy Resistance
Authors: Khan Husain Yar , Ge James , Nagasaka Misako , Aboukameel Amro , Mpilla Gabriel , Muqbil Irfana , Szlaczky Mark , Chaker Mahmoud , Baloglu Erkan , Landesman Yosef , Mohammad Ramzi M. , Azmi Asfar S. , Sukari Ammar
Published: December 2019

Lenvatinib is a multitargeted tyrosine kinase inhibitor (TKI) that shows improved median progression-free survival (PFS) in patients with thyroid carcinomas. However, virtually all patients ultimately progress, indicating the need for a better understanding of the mechanisms of resistance. Here, we examined the molecular profile of anaplastic thyroid cancer cells (8505C) exposed to lenvatinib and found that long-term exposure to lenvatinib caused phenotypic changes. Consistent with change toward mesenchymal morphology, activation of pro-survival signaling, nuclear exporter protein exportin 1 (XPO1) and Rho GTPase effector p21 activated kinases (PAK) was also observed. RNA-seq analysis showed that prolonged lenvatinib treatment caused alterations in numerous cellular pathways and several oncogenes such as CEACAM (carcinoembryonic antigen-related cell adhesion molecule) and NUPR1 (Nuclear protein 1) were also upregulated. Further, we evaluated the impact of XPO1 and PAK4 inhibition in the presence or absence of lenvatinib. Targeted inhibition of XPO1 and PAK4 could sensitize the 8505C cells to lenvatinib. Both XPO1 and PAK4 inhibitors, when combined with lenvatinib, showed superior anti-tumor activity in 8505C sub-cutaneous xenograft. These studies bring forward novel drug combinations to complement lenvatinib for treating anaplastic thyroid cancer. Such combinations may possibly reduce the chances of lenvatinib resistance in thyroid cancer patients.
Cell Wall Proteome of Wheat Grain Endosperm and Outer Layers at Two Key Stages of Early Development
Authors: Mehdi Cherkaoui , Virginie Lollier , Audrey Geairon , Axelle Bouder , Colette Larré , Hélène Rogniaux , Elisabeth Jamet , Fabienne Guillon , Mathilde Francin-Allami
Published: December 2019

The cell wall is an important compartment in grain cells that fulfills both structural and functional roles. It has a dynamic structure that is constantly modified during development and in response to biotic and abiotic stresses. Non-structural cell wall proteins (CWPs) are key players in the remodeling of the cell wall during events that punctuate the plant life. Here, a subcellular and quantitative proteomic approach was carried out to identify CWPs possibly involved in changes in cell wall metabolism at two key stages of wheat grain development: the end of the cellularization step and the beginning of storage accumulation. Endosperm and outer layers of wheat grain were analyzed separately as they have different origins (maternal and seed) and functions in grains. Altogether, 734 proteins with predicted signal peptides were identified (CWPs). Functional annotation of CWPs pointed out a large number of proteins potentially involved in cell wall polysaccharide remodeling. In the grain outer layers, numerous proteins involved in cutin formation or lignin polymerization were found, while an unexpected abundance of proteins annotated as plant invertase/pectin methyl esterase inhibitors were identified in the endosperm. In addition, numerous CWPs were accumulating in the endosperm at the grain filling stage, thus revealing strong metabolic activities in the cell wall during endosperm cell differentiation, while protein accumulation was more intense at the earlier stage of development in outer layers. Altogether, our work gives important information on cell wall metabolism during early grain development in both parts of the grain, namely the endosperm and outer layers. The wheat cell wall proteome is the largest cell wall proteome of a monocot species found so far.