bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Naturally Occurring Asbestos in the Area of Episcopia (Lucania, Southern Italy)
Authors: Bloise Andrea , Ricchiuti Claudia , Giorno Eugenia , Fuoco Ilaria , Zumpano Patrizia , Miriello Domenico , Apollaro Carmine , Crispini Alessandra , De Rosa Rosanna , Punturo Rosalda
Published: May 2019

Over the last few years, the risk to human health related to asbestos fiber exposure has been widely demonstrated by many studies. Serpentinites are the main rocks associated with naturally occurring asbestos (NOA). In order to investigate the presence of NOA, a mineralogical study was conducted on eleven serpentinite samples collected nearby the village of Episcopia (Lucania, Southern Italy). Various analytical techniques such as X-ray powder diffraction (XRPD), scanning electron microscopy combined with energy dispersive spectrometry (SEM-EDS) and derivative thermogravimetry (DTG) were used to determine the occurrence of asbestos minerals and to make morphological observations. Results pointed out that all of the samples contain asbestos minerals (e.g., tremolite, actinolite and chrysotile). Moreover, it was observed that both natural processes and human activity may disturb NOA-bearing outcrops and provoke the formation of potentially inhalable airborne dust causing the release of asbestos fibers into the environment, thereby increasing the risk to human health. For this reason, our study aims to highlight the requirement of a natural asbestos survey and periodic update in the area.
An Innovative Concept for a Walker with a Self-Locking Mechanism Using a Single Mechanical Approach
Authors: Lopes Stephane , Filipe Lúcia , Silva Rosana , Cruz Arménio , Parreira Pedro , Couto Filipa , Bernardes Rafael , Apóstolo João , Roseiro Luís , Malça Cândida
Published: May 2019

Background: The ageing process involves a natural degeneration of physiological function and can imply life constraints, namely during activities of daily life (ADL). Walking can be strongly affected by strength, gait, and balance changes, which affect quality of life. The quality of life of the older adult is associated with available solutions that contribute to an active and safe ageing process. Most of these solutions involve technical aids that should be adapted to older adults’ conditions. Aim: To identify the advantages and disadvantages of two-wheeled walkers and of two different self-locking systems designed and developed by the authors. Methods: Two studies were performed based on the possible walker combinations used, using a walker with no wheels (classic fixed walker), a two-wheeled walker with self-locking mechanism made of gears and a spring (Approach 1), and a two-wheeled walker with a self-locking mechanism which uses a single spring (Approach 2). These combinations were tested in two quasi-experimental studies with pre–post test design. Results: No significant differences in duration, gait speed, and Expanded Timed Get Up and Go (ETGUG) were found between the walkers, but there was a marginally significant difference in Physiological Cost Index (PCIs), which means that the energetic cost with Approach 1 was greater than that with Approach 2. Users reported a feeling of insecurity and more weight, although no significant differences were observed and they were found to be equivalent in terms of safety. Study 2 found an improvement in duration and gait speed in the ETGUG between the different types of self-locking systems. Conclusions: The PCI is higher in the two-wheeled walker models and with the self-locking mechanism. Approach 2 did not show better conditions of use than the other two walkers, and participants did not highlight its braking system. Although safety is similar among the three walkers, further studies are needed, and the braking system of the two-wheeled walker needs to be improved (Approach 2).
Factors Affecting Breastfeeding Practices in Sindh Province, Pakistan: A Secondary Analysis of Cross-Sectional Survey Data
Authors: Noh Jin-Won , Kim Young-mi , Akram Nabeel , Yoo Ki-Bong , Cheon Jooyoung , Lee Lena J. , Kwon Young Dae , Stekelenburg Jelle
Published: May 2019

Breastfeeding practices are critical for child health and growth. This paper investigates demographic factors, socioeconomic status, and information sources that affect breastfeeding practices in Sindh Province, Pakistan. A secondary analysis was performed of data on 10,028 women with a birth in the preceding two years who had participated in the 2013–14 Maternal and Child Health Program Indicator Survey. Multiple logistic regressions were used to test the association between breastfeeding status (ever breastfed and still breastfeeding) and age, number of living children, residence, education, wealth, information sources about breastfeeding, assistance during delivery, and place of delivery. Of the 9955 women included in the analysis, 97.9% had breastfed and 83.9% were still breastfeeding at the time of the survey. Being in the second, third, or fourth wealth quintiles and receiving breastfeeding information from relatives and friends were associated with ever breastfeeding. Women who were 35 years or older, living in a town/small city, higher maternal education, middle wealth quintile, and receiving breastfeeding information from the media were associated with still breastfeeding. The findings suggest the need to develop interventions considering maternal socioeconomic status and peer counseling interventions. Mass media campaigns to promote breastfeeding practices should be accompanied by governmental restrictions on the marketing of infant formula.
Comparison of Growth Curve Estimates of Infants in São Tomé Island, Africa, with the WHO Growth Standards: A Birth Cohort Study
Authors: Garzón Marisol , Papoila Ana Luísa , Alves Marta , Pereira-da-Silva Luís
Published: May 2019

This birth cohort study compared the infant growth curve estimates in São Tomé Island to the WHO growth standards. Despite this island belonging to a lower-middle-income country, there were several factors favorable for growth that were present. Four-hundred and seventy-five full-term singleton appropriate for-gestational-age infants were enrolled and followed-up to 24 months of age. Weight-for-age, length-for-age, weight-for-length, body mass index-for-age, head circumference-for-age, weight velocity, and length velocity curves were estimated and compared to the WHO standards. In the first 6 months of age, the weight gain was adequate in the presence of a high prevalence of exclusive breastfeeding. Thereafter, weight trajectories tracked close to the WHO standards, except for a progressive decline in the infants growing in higher percentiles, especially in girls. Median length at birth was below the median WHO standards, followed by an early postnatal velocity spurt, which probably reflected the transition from an unfavorable to a more favorable postnatal environment. Thereafter, linear growth faltering was observed without relevant deterioration up to 24 months of age, which was probably due to the presence of protective factors. These results may be useful to implement strategies to further approximate infant growth in São Tomé Island to the WHO standards.
Ion Channels and Thermosensitivity: TRP, TREK, or Both?
Authors: Lamas J. Antonio , Rueda-Ruzafa Lola , Herrera-Pérez Salvador
Published: May 2019

Controlling body temperature is a matter of life or death for most animals, and in mammals the complex thermoregulatory system is comprised of thermoreceptors, thermosensors, and effectors. The activity of thermoreceptors and thermoeffectors has been studied for many years, yet only recently have we begun to obtain a clear picture of the thermosensors and the molecular mechanisms involved in thermosensory reception. An important step in this direction was the discovery of the thermosensitive transient receptor potential (TRP) cationic channels, some of which are activated by increases in temperature and others by a drop in temperature, potentially converting the cells in which they are expressed into heat and cold receptors. More recently, the TWIK-related potassium (TREK) channels were seen to be strongly activated by increases in temperature. Hence, in this review we want to assess the hypothesis that both these groups of channels can collaborate, possibly along with other channels, to generate the wide range of thermal sensations that the nervous system is capable of handling.
A PTPmu Biomarker is Associated with Increased Survival in Gliomas
Authors: Johansen Mette L. , Vincent Jason , Gittleman Haley , Craig Sonya E. L. , Couce Marta , Sloan Andrew E. , Barnholtz-Sloan Jill S. , Brady-Kalnay Susann M.
Published: May 2019

An integrated approach has been adopted by the World Health Organization (WHO) for diagnosing brain tumors. This approach relies on the molecular characterization of biopsied tissue in conjunction with standard histology. Diffuse gliomas (grade II to grade IV malignant brain tumors) have a wide range in overall survival, from months for the worst cases of glioblastoma (GBM) to years for lower grade astrocytic and oligodendroglial tumors. We previously identified a change in the cell adhesion molecule PTPmu in brain tumors that results in the generation of proteolytic fragments. We developed agents to detect this cell surface-associated biomarker of the tumor microenvironment. In the current study, we evaluated the PTPmu biomarker in tissue microarrays and individual tumor samples of adolescent and young adult (n = 25) and adult (n = 69) glioma populations using a fluorescent histochemical reagent, SBK4-TR, that recognizes the PTPmu biomarker. We correlated staining with clinical data and found that high levels of the PTPmu biomarker correlate with increased survival of glioma patients, including those with GBM. Patients with high PTPmu live for 48 months on average, whereas PTPmu low patients live only 22 months. PTPmu high staining indicates a doubling of patient survival. Use of the agent to detect the PTPmu biomarker would allow differentiation of glioma patients with distinct survival outcomes and would complement current molecular approaches used in glioma prognosis.
Repeats in S1 Proteins: Flexibility and Tendency for Intrinsic Disorder
Authors: Machulin Andrey , Deryusheva Evgenia , Lobanov Mikhail , Galzitskaya Oxana
Published: May 2019

An important feature of ribosomal S1 proteins is multiple copies of structural domains in bacteria, the number of which changes in a strictly limited range from one to six. For S1 proteins, little is known about the contribution of flexible regions to protein domain function. We exhaustively studied a tendency for intrinsic disorder and flexibility within and between structural domains for all available UniProt S1 sequences. Using charge–hydrophobicity plot cumulative distribution function (CH-CDF) analysis we classified 53% of S1 proteins as ordered proteins; the remaining proteins were related to molten globule state. S1 proteins are characterized by an equal ratio of regions connecting the secondary structure within and between structural domains, which indicates a similar organization of separate S1 domains and multi-domain S1 proteins. According to the FoldUnfold and IsUnstruct programs, in the multi-domain proteins, relatively short flexible or disordered regions are predominant. The lowest percentage of flexibility is in the central parts of multi-domain proteins. Our results suggest that the ratio of flexibility in the separate domains is related to their roles in the activity and functionality of S1: a more stable and compact central part in the multi-domain proteins is vital for RNA interaction, terminals domains are important for other functions.
Cadmium Complexed with β2-Microglubulin, Albumin and Lipocalin-2 rather than Metallothionein Cause Megalin:Cubilin Dependent Toxicity of the Renal Proximal Tubule
Authors: Fels Johannes , Scharner Bettina , Zarbock Ralf , Zavala Guevara Itzel Pamela , Lee Wing-Kee , Barbier Olivier C. , Thévenod Frank
Published: May 2019

Cadmium (Cd2+) in the environment is a significant health hazard. Chronic low Cd2+ exposure mainly results from food and tobacco smoking and causes kidney damage, predominantly in the proximal tubule. Blood Cd2+ binds to thiol-containing high (e.g., albumin, transferrin) and low molecular weight proteins (e.g., the high-affinity metal-binding protein metallothionein, β2-microglobulin, α1-microglobulin and lipocalin-2). These plasma proteins reach the glomerular filtrate and are endocytosed at the proximal tubule via the multiligand receptor complex megalin:cubilin. The current dogma of chronic Cd2+ nephrotoxicity claims that Cd2+-metallothionein endocytosed via megalin:cubilin causes renal damage. However, a thorough study of the literature strongly argues for revision of this model for various reasons, mainly: (i) It relied on studies with unusually high Cd2+-metallothionein concentrations; (ii) the KD of megalin for metallothionein is ~105-times higher than (Cd2+)-metallothionein plasma concentrations. Here we investigated the uptake and toxicity of ultrafiltrated Cd2+-binding protein ligands that are endocytosed via megalin:cubilin in the proximal tubule. Metallothionein, β2-microglobulin, α1-microglobulin, lipocalin-2, albumin and transferrin were investigated, both as apo- and Cd2+-protein complexes, in a rat proximal tubule cell line (WKPT-0293 Cl.2) expressing megalin:cubilin at low passage, but is lost at high passage. Uptake was determined by fluorescence microscopy and toxicity by MTT cell viability assay. Apo-proteins in low and high passage cells as well as Cd2+-protein complexes in megalin:cubilin deficient high passage cells did not affect cell viability. The data prove Cd2+-metallothionein is not toxic, even at >100-fold physiological metallothionein concentrations in the primary filtrate. Rather, Cd2+-β2-microglobulin, Cd2+-albumin and Cd2+-lipocalin-2 at concentrations present in the primary filtrate are taken up by low passage proximal tubule cells and cause toxicity. They are therefore likely candidates of Cd2+-protein complexes damaging the proximal tubule via megalin:cubilin at concentrations found in the ultrafiltrate.
Renal Regenerative Potential of Extracellular Vesicles Derived from miRNA-Engineered Mesenchymal Stromal Cells
Authors: Tapparo Marta , Bruno Stefania , Collino Federica , Togliatto Gabriele , Deregibus Maria Chiara , Provero Paolo , Wen Sicheng , Quesenberry Peter J. , Camussi Giovanni
Published: May 2019

Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) possess pro-regenerative potential in different animal models with renal injury. EVs contain different molecules, including proteins, lipids and nucleic acids. Among the shuttled molecules, miRNAs have a relevant role in the pro-regenerative effects of EVs and are a promising target for therapeutic interventions. The aim of this study was to increase the content of specific miRNAs in EVs that are known to be involved in the pro-regenerative effect of EVs, and to assess the capacity of modified EVs to contribute to renal regeneration in in vivo models with acute kidney injuries. To this purpose, MSCs were transiently transfected with specific miRNA mimics by electroporation. Molecular analyses showed that, after transfection, MSCs and derived EVs were efficiently enriched in the selected miRNAs. In vitro and in vivo experiments indicated that EVs engineered with miRNAs maintained their pro-regenerative effects. Of relevance, engineered EVs were more effective than EVs derived from naïve MSCs when used at suboptimal doses. This suggests the potential use of a low amount of EVs (82.5 × 106) to obtain the renal regenerative effect.
A Comprehensive Review on Current Advances in Peptide Drug Development and Design
Authors: Lee Andy Chi-Lung , Harris Janelle Louise , Khanna Kum Kum , Hong Ji-Hong
Published: May 2019

Protein–protein interactions (PPIs) execute many fundamental cellular functions and have served as prime drug targets over the last two decades. Interfering intracellular PPIs with small molecules has been extremely difficult for larger or flat binding sites, as antibodies cannot cross the cell membrane to reach such target sites. In recent years, peptides smaller size and balance of conformational rigidity and flexibility have made them promising candidates for targeting challenging binding interfaces with satisfactory binding affinity and specificity. Deciphering and characterizing peptide–protein recognition mechanisms is thus central for the invention of peptide-based strategies to interfere with endogenous protein interactions, or improvement of the binding affinity and specificity of existing approaches. Importantly, a variety of computation-aided rational designs for peptide therapeutics have been developed, which aim to deliver comprehensive docking for peptide–protein interaction interfaces. Over 60 peptides have been approved and administrated globally in clinics. Despite this, advances in various docking models are only on the merge of making their contribution to peptide drug development. In this review, we provide (i) a holistic overview of peptide drug development and the fundamental technologies utilized to date, and (ii) an updated review on key developments of computational modeling of peptide–protein interactions (PepPIs) with an aim to assist experimental biologists exploit suitable docking methods to advance peptide interfering strategies against PPIs.
Quantification of 3D Brain Microangioarchitectures in an Animal Model of Krabbe Disease
Authors: Righi Marco , Belleri Mirella , Presta Marco , Giacomini Arianna
Published: May 2019

We performed a three-dimensional (3D) analysis of the microvascular network of the cerebral cortex of twitcher mice (an authentic model of Krabbe disease) using a restricted set of indexes that are able to describe the arrangement of the microvascular tree in CD31-stained sections. We obtained a near-linear graphical “fingerprint” of the microangioarchitecture of wild-type and twitcher animals that describes the amounts, spatial dispersion, and spatial relationships of adjacent classes of caliber-filtered microvessels. We observed significant alterations of the microangioarchitecture of the cerebral cortex of twitcher mice, whereas no alterations occur in renal microvessels, which is keeping with the observation that kidney is an organ that is not affected by the disease. This approach may represent an important starting point for the study of the microvascular changes that occur in the central nervous system (CNS) under different physiopathological conditions.
Genetic Transformation and Green Fluorescent Protein Labeling in Ceratocystis paradoxa from Coconut
Authors: Niu Xiaoqing , Pei Mengtian , Liang Chenyu , Lv Yuexiao , Wu Xinyi , Zhang Ruina , Lu Guodong , Yu Fengyu , Zhu Hui , Qin Weiquan
Published: May 2019

Ceratocystis paradoxa, the causal agent of stem-bleeding disease of the coconut palm, causes great losses to the global coconut industry. As the mechanism of pathogenicity of C. paradoxa has not been determined, an exogenous gene marker was introduced into the fungus. In this study, pCT74-sGFP, which contains the green fluorescent protein (GFP) gene, and the hygromycin B resistance gene as a selective marker, was used as an expression vector. Several protoplast release buffers were compared to optimize protoplast preparation. The plasmid pCT74-sGFP was successfully transformed into the genome of C. paradoxa, which was verified using polymerase chain reaction and green fluorescence detection. The transformants did not exhibit any obvious differences from the wild-type isolates in terms of growth and morphological characteristics. Pathogenicity tests showed that the transformation process did not alter the virulence of the X-3314 C. paradoxa strain. This is the first report on the polyethylene glycol-mediated transformation of C. paradoxa carrying a ‘reporter’ gene GFP that was stably and efficiently expressed in the transformants. These findings provide a basis for future functional genomics studies of C. paradoxa and offer a novel opportunity to track the infection process of C. paradoxa.
Furosine, a Maillard Reaction Product, Triggers Necroptosis in Hepatocytes by Regulating the RIPK1/RIPK3/MLKL Pathway
Authors: Li Huiying , Wang Yizhen , Yang Huaigu , Zhang Yangdong , Xing Lei , Wang Jiaqi , Zheng Nan
Published: May 2019

As one of the typical Maillard reaction products, furosine has been widely reported in a variety of heat-processed food. Though furosine was shown to be toxic on organs, its toxicity mechanism is still unclear. The present study aimed to investigate the toxicity mechanism of furosine in liver tissue. An intragastric gavage mice model (42-day administration, 0.1/0.25/0.5 g/kg of furosine per day) and a mice primary hepatocyte model were employed to investigate the toxicity mechanism of furosine on mice liver tissue. A metabonomics analysis of mice liver, serum, and red blood cells (RBC) was performed. The special metabolic mediator of furosine, lysophosphatidylcholine 18:0 (LPC (18:0)) was identified. Then, the effect of the upstream gene phospholipase A2 gamma (PLA2-3) on LPC (18:0), as well as the effect of furosine (100 mg/L) on the receptor-interacting serine/threonine-protein kinase (RIPK)1/RIPK3/mixed lineage kinase domain-like protein (MLKL) pathway and inflammatory factors, was determined in liver tissue and primary hepatocytes. PLA2-3 was found to regulate the level of LPC (18:0) and activate the expression of RIPK1, RIPK3, P-MLKL, and of the inflammatory factors including tumor necrosis factor α (TNF-α) and interleukin (IL-1β), both in liver tissue and in primary hepatocytes. Upon treatment with furosine, the upstream sensor PLA2-3 activated the RIPK1/RIPK3/MLKL necroptosis pathway and caused inflammation by regulating the expression of LPC (18:0), which further caused liver damage.
Leptin and Immunological Profile in Obesity and Its Associated Diseases in Dogs
Authors: Cortese Laura , Terrazzano Giuseppe , Pelagalli Alessandra
Published: May 2019

Growing scientific evidence has unveiled increased incidences of obesity in domestic animals and its influence on a plethora of associated disorders. Leptin, an adipokine regulating body fat mass, represents a key molecule in obesity, able to modulate immune responses and foster chronic inflammatory response in peripheral tissues. High levels of cytokines and inflammatory markers suggest an association between inflammatory state and obesity in dogs, highlighting the parallelism with humans. Canine obesity is a relevant disease always accompanied with several health conditions such as inflammation, immune-dysregulation, insulin resistance, pancreatitis, orthopaedic disorders, cardiovascular disease, and neoplasia. However, leptin involvement in many disease processes in veterinary medicine is poorly understood. Moreover, hyperleptinemia as well as leptin resistance occur with cardiac dysfunction as a consequence of altered cardiac mitochondrial metabolism in obese dogs. Similarly, leptin dysregulation seems to be involved in the pancreatitis pathophysiology. This review aims to examine literature concerning leptin and immunological status in obese dogs, in particular for the aspects related to obesity-associated diseases.
Electro-Kinetic Instability in a Laminar Boundary Layer Next to an Ion Exchange Membrane
Authors: Magnico Pierre
Published: May 2019

The electro-kinetic instability in a pressure driven shear flow near an ion exchange membrane is considered. The electrochemical system, through which an electrical potential drop is applied, consists in a polarization layer in contact with the membrane and a bulk. The numerical investigation contained two aspects: analysis of the instability modes and description of the Lagrangian transport of fluid and ions. Regarding the first aspect, the modes were analyzed as a function of the potential drop. The analysis revealed how the spatial distribution of forces controls the dynamics of vortex association and dissociation. In particular, the birth of a counter-clockwise vortex between two clockwise vortices, and the initiation of clusters constituting one or two envelopes wrapping a vortex group, were examined. In regards to the second aspect, the trajectories were computed with the fourth order Runge Kutta scheme for the time integration and with the biquadratric upstream scheme for the spatial and time interpolation of the fluid velocity and the ion flux. The results for the periodic mode showed two kinds of trajectories: the trochoidal motion and the longitudinal one coupled with a periodic transverse motion. For the aperiodic modes, other mechanisms appeared, such as ejection from the mixing layer, trapping by a growing vortex or merging vortices. The analysis of the local velocity field, the vortices’ shape, the spatial distribution of the forces and the ion flux components explained these trajectories.
Effects of Water Immersion and Soil Moisture Content on Larval and Pupal Survival of Bactrocera minax (Diptera: Tephritidae)
Authors: Li Zaiyuan , Chambi Consolatha , Du Tianhua , Huang Cong , Wang Fulian , Zhang Guifen , Li Chuanren , Juma Kayeke Mohamed
Published: May 2019

Bactrocera minax, one of the most devastating citrus pests in Asia, has two developmental stages (mature larva and pupa) that complete their life cycle in the soil. Currently, southern China has a climate with abundant autumn rains, and soil moisture can be a major factor affecting the survival of larvae and pupae of B. minax. In the present study, we evaluated the effects of water immersion and high soil moisture content on the development of mature larvae and pupae of B. minax. When immersed in water for 1 d, 100% of mature larvae of B. minax were knocked out. When larvae were immersed for less than 6 d, however, more than 92% of knocked-out larvae recovered within 24 h. The days of water immersion with 50% and 90% recovery ratios (indicated as RD50 and RD90) were 10.3 d and 6.4 d, respectively. When larvae were immersed less than 6 d, the mortality ratios of larvae were not significantly different from those that were not immersed at all. The days of immersion causing 50% and 90% mortality of larvae (MD50 and MD90, respectively) were 7.6 d and 11.1 d, respectively. The pupation ratios of larvae were also observed to be not significantly different compared to non-immersion, and the days of immersion causing 50% and 90% pupation (PD50 and PD90, respectively) were 6.6 d and 0.8 d, respectively. Larval respiration rates were reduced after water immersion as a strategy for larval survival. High water content was not detrimental to pupae of B. minax. Adult emergence did not significantly decrease in soil with high water content, even though pupae were under those conditions for 161–175 d. The respiration rates of pupae were lower in soil with different moisture levels and were not significantly different, which ensured the survival of pupae in high water content. Reduced respiration rate is a strategy for survival of larvae and pupae, and remarkable tolerance to high moisture conditions could explain the high rate of spread and geographical distribution of B. minax. The results of this study provide a reference for the occurrence and control of B. minax.
Phosphoproteins Involved in the Inhibition of Apoptosis and in Cell Survival in the Leiomyoma
Authors: Ura Blendi , Monasta Lorenzo , Arrigoni Giorgio , Battisti Ilaria , Licastro Danilo , Di Lorenzo Giovanni , Romano Federico , Aloisio Michelangelo , Peterlunger Isabel , Stabile Guglielmo , Scrimin Federica , Ricci Giuseppe
Published: May 2019

Uterine leiomyomas are benign smooth muscle cell tumors originating from the myometrium. In this study we focus on leiomyoma and normal myometrium phosphoproteome, to identify differentially phosphorylated proteins involved in tumorigenic signaling pathways, and in anti-apoptotic processes and cell survival. We obtained paired tissue samples of seven leiomyomas and adjacent myometria and analyzed the phosphoproteome by two-dimensional gel electrophoresis (2-DE) combined with immobilized metal affinity chromatography (IMAC) and Pro-Q Diamond phosphoprotein gel stain. We used mass spectrometry for protein identification and Western blotting for 2-DE data validation. Quantities of 33 proteins enriched by the IMAC approach were significantly different in the leiomyoma if compared to the myometrium. Bioinformatic analysis revealed ten tumorigenic signaling pathways and four phosphoproteins involved in both the inhibition of apoptosis and cell survival. Our study highlights the involvement of the phosphoproteome in leiomyoma growth. Further studies are needed to understand the role of phosphorylation in leiomyoma. Our data shed light on mechanisms that still need to be ascertained, but could open the path to a new class of drugs that not only can block the growth, but could also lead to a significant reduction in tumor size.
Genome-Wide Association between the 2q33.1 Locus and Intracranial Aneurysm Susceptibility: An Updated Meta-Analysis Including 18,019 Individuals
Authors: Hong Eun Pyo , Kim Bong Jun , Jeon Jin Pyeong
Published: May 2019

Previous genome-wide association studies did not show a consistent association between the BOLL gene (rs700651, 2q33.1) and intracranial aneurysm (IA) susceptibility. We aimed to perform an updated meta-analysis for the potential IA-susceptibility locus in large-scale multi-ethnic populations. We conducted a systematic review of studies identified by an electronic search from January 1990 to March 2019. The overall estimates of the “G” allele of rs700651, indicating IA susceptibility, were calculated under the fixed- and random-effect models using the inverse-variance method. Subsequent in silico function and cis-expression quantitative trait loci (cis-eQTL) analyses were performed to evaluate biological functions and genotype-specific expressions in human tissues. We included 4513 IA patients and 13,506 controls from five studies with seven independent populations: three European-ancestry, three Japanese, and one Korean population. The overall result showed a genome-wide significance threshold between rs700651 and IA susceptibility after controlling for study heterogeneity (OR = 1.213, 95% CI: 1.135–1.296). Subsequent cis-eQTL analysis showed significant genome-wide expressions in three human tissues, i.e., testis (p = 8.04 × 10−15 for ANKRD44), tibial nerves (p = 3.18 × 10−10 for SF3B1), and thyroid glands (p = 4.61 × 10−9 for SF3B1). The rs700651 common variant of the 2q33.1 region may be involved in genetic mechanisms that increase the risk of IA and may play crucial roles in regulatory functions.
Gut Microbial Composition and Function Are Altered in Patients with Early Rheumatoid Arthritis
Authors: Jeong Yunju , Kim Ji-Won , You Hyun Ju , Park Sang-Jun , Lee Jennifer , Ju Ji Hyeon , Park Myeong Soo , Jin Hui , Cho Mi-La , Kwon Bin , Park Sung-Hwan , Ji Geun Eog
Published: May 2019

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation of the joints and extra-articular manifestations. Recent studies have shown that microorganisms affect RA pathogenesis. However, few studies have examined the microbial distribution of early RA patients, particularly female patients. In the present study, we investigated the gut microbiome profile and microbial functions in early RA female patients, including preclinical and clinically apparent RA cases. Changes in microbiological diversity, composition, and function in each group were analyzed using quantitative insights into microbial ecology (QIIME) and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt). The results revealed the dysbiosis due to decreased diversity in the early RA patients compared with healthy subjects. There were significant differences in the microbial distribution of various taxa from phylum to genus levels between healthy subjects and early RA patients. Phylum Bacteroidetes was enriched in early RA patients, while Actinobacteria, including the genus Collinsella, was enriched in healthy subjects. Functional analysis based on clusters of orthologous groups revealed that the genes related to the biosynthesis of menaquinone, known to be derived from gram-positive bacteria, were enriched in healthy subjects, while iron transport-related genes were enriched in early RA patients. Genes related to the biosynthesis of lipopolysaccharide, the gram-negative bacterial endotoxin, were enriched in clinically apparent RA patients. The obvious differences in microbial diversity, taxa, and associated functions of the gut microbiota between healthy subjects and early RA patients highlight the involvement of the gut microbiome in the early stages of RA.
Diverse Action of Selected Statins on Skeletal Muscle Cells—An Attempt to Explain the Protective Effect of Geranylgeraniol (GGOH) in Statin-Associated Myopathy (SAM)
Authors: Jaśkiewicz Anna , Pająk Beata , Łabieniec-Watała Magdalena , Palma Clara De , Orzechowski Arkadiusz
Published: May 2019

The present study is centered on molecular mechanisms of the cytoprotective effect of geranylgeraniol (GGOH) in skeletal muscle harmed by statin-associated myopathy (SAM). GGOH via autophagy induction was purportedly assumed to prevent skeletal muscle viability impaired by statins, atorvastatin (ATR) or simvastatin (SIM). The C2C12 cell line was used as the ‘in vitro’ model of muscle cells at different stages of muscle formation, and the effect of ATR or SIM on the cell viability, protein expression and mitochondrial respiration were tested. Autophagy seems to be important for the differentiation of muscle cells; however, it did not participate in the observed GGOH cytoprotective effects. We showed that ATR- and SIM-dependent loss in cell viability was reversed by GGOH co-treatment, although GGOH did not reverse the ATR-induced drop in the cytochrome c oxidase protein expression level. It has been unambiguously revealed that the mitochondria of C2C12 cells are not sensitive to SIM, although ATR effectively inhibits mitochondrial respiration. GGOH restored proper mitochondria functioning. Apoptosis might, to some extent, explain the lower viability of statin-treated myotubes as the pan-caspase inhibitor, N-Benzyloxycarbonyl-Val-Ala-Asp(O-Me) fluoromethyl ketone (Z-VAD-FMK), partly reversed ATR- or SIM-induced cytotoxic effects; however, it does not do so in conjunction with caspase-3. It appears that the calpain inhibitor, N-Acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLM), restored the viability that was reduced by ATR and SIM (p < 0.001). GGOH prevents SAM, in part, as a consequence of a caspase-3 independent pathway, probably by calpain system inactivation.
Analysis of Tumor Angiogenesis and Immune Microenvironment in Non-Functional Pituitary Endocrine Tumors
Authors: Sato Mizuto , Tamura Ryota , Tamura Haruka , Mase Taro , Kosugi Kenzo , Morimoto Yukina , Yoshida Kazunari , Toda Masahiro
Published: May 2019

Cavernous sinus (CS) invasion is an aggressive behavior exhibited by pituitary neuroendocrine tumors (PitNETs). The cause of CS invasion in PitNETs has not been fully elucidated. The tumor immune microenvironment, known to promote aggressive behavior in various types of tumors, has not been examined for PitNETs. Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) signaling is strongly associated with the tumor immune microenvironment. In the present study, these molecular and histopathological characteristics were examined in invasive non-functional PitNETs (NF-PitNETs). Twenty-seven patients with newly diagnosed NF-PitNETs (with CS invasion: 17, without CS invasion: 10) were analyzed by immunohistochemistry for VEGF-A/VEGFR1 and 2, hypoxia-inducible Factor (HIF), tumor-infiltrating lymphocytes, immunosuppressive cells including regulatory T cells (Tregs) and tumor-associated macrophages (TAMs), and immune checkpoint molecules. Previously validated tumor proliferation markers including mitotic count, Ki-67 index, and p53 were also analyzed for their expressions in NF-PitNETs. VEGF-A and VEGFR1 were expressed on not only vascular endothelial cells, but also on tumor cells. The expressions of VEGF-A and VEGFR1 were significantly higher in NF-PitNETs with CS invasion. The number of TAMs and the expression of PD-L1 were also significantly higher in NF-PitNETs with CS invasion than in NF-PitNETs without CS invasion. The high expression of VEGF-A and VEGFR1 and associated immunosuppressive microenvironment were observed in NF-PitNETs with CS invasion, suggesting that a novel targeted therapy can be applied.
Effects of Short-Term Laser Beam Heating on the Absorptivity of Steel Sheets
Authors: Kügler Helge
Published: May 2019

The efficiency of laser beam processes basically depends on the efficiency of the laser beam source and the efficiency of the irradiated material’s energy absorption. This absorptivity can be influenced by the surface condition. Besides coating or boundary layers, the surface topography is decisive. In this study, the effects of various time–temperature distributions on the absorptivity changes of steel sheets were investigated. For this purpose, three steels were chosen, namely, a stainless steel, a spring steel, and a hot work tool steel. Pre- and post-process characterizations of the absorptivity and surface topography were performed. Controlled heating with a laser beam was carried out using temperatures between 700 and 1200 °C and durations between 2 and 34 s. In order to compare the influences of these heating procedures on the absorptivity, a characteristic value, the temperature‑compensated time, was introduced. It is shown that the surface roughness was influenced by laser irradiation but inadequately describes the increase of absorptivity. The changes in absorptivity are attributed to oxidation, which had an influence on the topography in a sub‑micrometer range. Moreover, a saturation effect is observed for intense heatings. Furthermore, it is shown that the temperature‑compensated time is a suitable value to describe absorptivity changes caused by short‑term heating.
A Universally Primed-Polymerase Chain Reaction (UP-PCR) Marker to Discriminate Clonostachys rosea ACM941 from Related Strains
Authors: Demissie Zerihun A. , Brown William G. , Loewen Michele C.
Published: May 2019

Clonostachys rosea strain ACM941 is an effective biocontrol agent against several crop diseases including Fusarium head blight. In anticipation of its increased relevance going forward, the development of a reliable DNA-based molecular marker to track it is essential. Universally primed-PCR (UP-PCR) has been used successfully to differentiate other C. rosea strains. Herein, the development of a UP-PCR marker for ACM941 is described. A combination of two primers (AS15 and L45) produced a ~450 bp fragment that was unique to ACM941 compared to other commercial biocontrol agents. Primers subsequently designed based on the obtained fragment also produced a similarly unique band from ACM941 alone. BLAST analysis of the amplified sequence did not yield any homologous sequence in available online databases or within the closely related C. rosea IK726 and CBS125111 strains’ genomes. The specificity of this marker for ACM941 was validated against ten additional C. rosea strains isolated from Canada, with ACM941 producing the brightest band. Taken together, these results imply that the UP-PCR primers AS15 and L45 and the amplified fragment can be used to detect and monitor the ACM941 strain after its release into the environment.
Chemistry of Homocysteine Thiolactone in A Prebiotic Perspective
Authors: Shalayel Ibrahim , Vallée Yannick
Published: May 2019

Homocysteine is a non-proteinogenic sulfur-containing amino acid. Like cysteine, it can form disulfide bridges and complex metallic cations. It is also closely related to methionine, the first amino acid in the synthesis of all contemporary proteins. Furthermore, its cyclized form, a five-membered ring thiolactone, is stable in acidic and neutral water. Here, we demonstrate that this thiolactone may have been formed in the primitive ocean directly from the Strecker precursor of homocysteine, an aminonitrile. Even though it is poorly reactive, this thiolactone may be open by some amines, yielding amides which, in turn, could be the precursors of longer peptides.
Exploring the Kamchatka Geothermal Region in the Context of Life’s Beginning
Authors: Kompanichenko Vladimir N.
Published: May 2019

This article is a brief review of research in the Kamchatka geothermal region initiated by David Deamer and the author in 1999. Results obtained over the last 20 years are described, including a seminal experiment in which biologically important organic compounds were dispersed in a hot spring to determine their fate. Other investigations include ionic and organic composition of hydrothermal water, the source of hydrothermally generated oil, and pressure–temperature oscillations in hydrothermal systems. The relation of these results to research on the origin of life is discussed.
Micro-Pitting and Wear Assessment of PAO vs Mineral-Based Engine Oil Operating under Mixed Lubrication Conditions: Effects of Lambda, Roughness Lay and Sliding Direction
Authors: Vrček Aleks , Hultqvist Tobias , Baubet Yannick , Björling Marcus , Marklund Pär , Larsson Roland
Published: May 2019

Under certain operating conditions, rolling contacts have been shown to experience some challenges when lubricated with engine oils containing zinc dialkyldithophosphate (ZDDP) anti-wear additive. In order to better understand the main damage mechanisms during various operating conditions, further studies are needed. This article studies micro-pitting and wear damages of bearing steel surfaces under mixed lubrication conditions in a ball-on-disc setup, lubricated with different engine oils. Based on the results, micro-pitting and wear damage is shown to be highly case-dependent. In general, PAO-based engine oil tends to eliminate micro-pitting damage compared to mineral-based engine oil at less severe lubricating conditions. Moreover, a critical lambda was found for both oils, where the highest micro-pitting damage was observed.
Strong and Ductile Electroplated Heterogeneous Bulk Nanostructured Nickel
Authors: Jiang Yaoyao , Yi Jun , Hu Kai , Zhao Jing , Huang Bo , Jia Yandong , Wang Gang
Published: May 2019

Porosity-free bulk nanostructured nickel cannot be fabricated by conventional electroplating due to hydrogen bubbling at the cathode. Here, we developed a cathode-rotating electroplating technique to remove the bubbles in order to obtain millimeter-scale nanostructured nickel rods with low porosity. The grain sizes ranged from 20 to 300 nm. The range produced by the new technique was broader than those that have been reported. The heterogeneous microstructure contributed to high work hardening rate, yield strength, and ductility of the rods in tension. The ductility was larger than electroplated thin nickel film with comparable ultimate strength in the literature. Dislocations accumulated at pre-existing twins, grain boundaries, and at the grain interior mediated the plastic deformation of the rods.
Evaluation of Copper-Based Alloy (C93200) Composites Reinforced with Marble Dust Developed by Stir Casting under Vacuum Environment
Authors: Rajak Santosh Kumar , Aherwar Amit , Unune Deepak Rajendra , Mia Mozammel , Pruncu Catalin I.
Published: May 2019

Copper-based alloy (C93200) composites reinforced with a different weight percentage of marble dust particles (1.5, 3, 4.5, and 6 wt.%) were developed by stir casting method under vacuum environment. By using this type of reinforcement, it was possible to detect a suitable material for bearing applications. The manufactured material was characterized for its mechanical properties using a micro-hardness tester. A universal INSTRON-5967 machine was used to detect the yield and tensile strength. Further the hardness features were measured using a Walter Uhl model machine, whereby the wear characteristics were simulated under the pin-on-disc tribometer under different working conditions in ambient temperature (23 °C). Next, the preference selection index (PSI) technique that considers multi-criteria decision-making was proposed to validate which material was the best candidate. For the selection of material criteria, some specific material intrinsic properties—such as, density, void fraction, hardness resistance along with tensile, compressive, and flexural strength—were proposed and the surface characteristics linked to friction coefficients along wear properties. It was found that the novel composite material containing 4.5 wt.% of marble dust provided the best combination of properties and is a suitable candidate material for bearing applications.
The Fate of Osteoblast-Like MG-63 Cells on Pre-Infected Bactericidal Nanostructured Titanium Surfaces
Authors: Wandiyanto Jason V. , Truong Vi Khanh , Al Kobaisi Mohammad , Juodkazis Saulius , Thissen Helmut , Bazaka Olha , Bazaka Kateryna , Crawford Russell J. , Ivanova Elena P.
Published: May 2019

Biomaterials that have been newly implanted inside the body are the substratum targets for a “race for the surface”, in which bacterial cells compete against eukaryotic cells for the opportunity to colonize the surface. A victory by the former often results in biomaterial-associated infections, which can be a serious threat to patient health and can undermine the function and performance of the implant. Moreover, bacteria can often have a ‘head start’ if implant contamination has taken place either prior to or during the surgery. Current prevention and treatment strategies often rely on systemic antibiotic therapies, which are becoming increasingly ineffective due to a growing prevalence of antibiotic-resistant bacteria. Nanostructured surfaces that kill bacteria by physically rupturing bacterial cells upon contact have recently emerged as a promising solution for the mitigation of bacterial colonization of implants. Furthermore, these nanoscale features have been shown to enhance the adhesion and proliferation of eukaryotic cells, which is a key to, for example, the successful osseointegration of load-bearing titanium implants. The bactericidal activity and biocompatibility of such nanostructured surfaces are often, however, examined separately, and it is not clear to what extent bacterial cell-surface interactions would affect the subsequent outcomes of host-cell attachment and osseointegration processes. In this study, we investigated the ability of bactericidal nanostructured titanium surfaces to support the attachment and growth of osteoblast-like MG-63 human osteosarcoma cells, despite them having been pre-infected with pathogenic bacteria. MG-63 is a commonly used osteoblastic model to study bone cell viability, adhesion, and proliferation on the surfaces of load-bearing biomaterials, such as titanium. The nanostructured titanium surfaces used here were observed to kill the pathogenic bacteria, whilst simultaneously enhancing the growth of MG-63 cells in vitro when compared to that occurring on sterile, flat titanium surfaces. These results provide further evidence in support of nanostructured bactericidal surfaces being used as a strategy to help eukaryotic cells win the “race for the surface” against bacterial cells on implant materials.
Viscous and Failure Mechanisms in Polymer Networks: A Theoretical Micromechanical Approach
Authors: Brighenti Roberto , Artoni Federico , Cosma Mattia Pancrazio
Published: May 2019

Polymeric materials typically present a complex response to mechanical actions; in fact, their behavior is often characterized by viscous time-dependent phenomena due to the network rearrangement and damage induced by chains’ bond scission, chains sliding, chains uncoiling, etc. A simple yet reliable model—possibly formulated on the basis of few physically-based parameters—accounting for the main micro-scale micromechanisms taking place in such a class of materials is required to properly describe their response. In the present paper, we propose a theoretical micromechanical approach rooted in the network’s chains statistics which allows us to account for the time-dependent response and for the chains failure of polymer networks through a micromechanics formulation. The model is up-scaled to the mesoscale level by integrating the main field quantities over the so-called ‘chains configuration space’. After presenting the relevant theory, its reliability is verified through the analysis of some representative tests, and some final considerations are drawn.