bluuebunny/crossref_metadata_2025 huggingface dataset:
Automatic Gene Function Prediction in the 2020’s
Authors: Makrodimitris Stavros , van Ham Roeland C. H. J. , Reinders Marcel J. T.
Published: October 2020

The current rate at which new DNA and protein sequences are being generated is too fast to experimentally discover the functions of those sequences, emphasizing the need for accurate Automatic Function Prediction (AFP) methods. AFP has been an active and growing research field for decades and has made considerable progress in that time. However, it is certainly not solved. In this paper, we describe challenges that the AFP field still has to overcome in the future to increase its applicability. The challenges we consider are how to: (1) include condition-specific functional annotation, (2) predict functions for non-model species, (3) include new informative data sources, (4) deal with the biases of Gene Ontology (GO) annotations, and (5) maximally exploit the GO to obtain performance gains. We also provide recommendations for addressing those challenges, by adapting (1) the way we represent proteins and genes, (2) the way we represent gene functions, and (3) the algorithms that perform the prediction from gene to function. Together, we show that AFP is still a vibrant research area that can benefit from continuing advances in machine learning with which AFP in the 2020s can again take a large step forward reinforcing the power of computational biology.
Genomic Diversity in Sporadic Breast Cancer in a Latin American Population
Authors: Brignoni Lucía , Cappetta Mónica , Colistro Valentina , Sans Mónica , Artagaveytia Nora , Bonilla Carolina , Bertoni Bernardo
Published: October 2020

Among Latin American women, breast cancer incidences vary across populations. Uruguay and Argentina have the highest rates in South America, which are mainly attributed to strong, genetic European contributions. Most genetic variants associated with breast cancer were described in European populations. However, the vast majority of genetic contributors to breast cancer risk remain unknown. Here, we report the results of a candidate gene association study of sporadic breast cancer in 176 cases and 183 controls in the Uruguayan population. We analyzed 141 variants from 98 loci that have been associated with overall breast cancer risk in European populations. We found weak evidence for the association of risk variants rs294174 (ESR1), rs16886165 (MAP3K1), rs2214681 (CNTNAP2), rs4237855 (VDR), rs9594579 (RANKL), rs8183919 (PTGIS), rs2981582 (FGFR2), and rs1799950 (BRCA1) with sporadic breast cancer. These results provide useful insight into the genetic susceptibility to sporadic breast cancer in the Uruguayan population and support the use of genetic risk scores for individualized screening and prevention.
Dissecting the Genetic Regulation of Yeast Growth Plasticity in Response to Environmental Changes
Authors: Zan Yanjun , Carlborg Örjan
Published: October 2020

Variable individual responses to environmental changes, such as phenotype plasticity, are heritable, with some genotypes being robust and others plastic. This variation for plasticity contributes to variance in complex traits as genotype-by-environment interactions (G × E). However, the genetic basis of this variability in responses to the same external stimuli is still largely unknown. In an earlier study of a large haploid segregant yeast population, genotype-by-genotype-by-environment interactions were found to make important contributions to the release of genetic variation in growth responses to alterations of the growth medium. Here, we explore the genetic basis for heritable variation of different measures of phenotype plasticity in the same dataset. We found that the central loci in the environmentally dependent epistatic networks were associated with overall measures of plasticity, while the specific measures of plasticity identified a more diverse set of loci. Based on this, a rapid one-dimensional genome-wide association (GWA) approach to overall plasticity is proposed as a strategy to efficiently identify key epistatic loci contributing to the phenotype plasticity. The study thus provided both analytical strategies and a deeper understanding of the complex genetic regulation of phenotype plasticity in yeast growth.
Platinum-Quality Mitogenome Haplotypes from United States Populations
Authors: Taylor Cassandra R. , Kiesler Kevin M. , Sturk-Andreaggi Kimberly , Ring Joseph D. , Parson Walther , Schanfield Moses , Vallone Peter M. , Marshall Charla
Published: October 2020

A total of 1327 platinum-quality mitochondrial DNA haplotypes from United States (U.S.) populations were generated using a robust, semi-automated next-generation sequencing (NGS) workflow with rigorous quality control (QC). The laboratory workflow involved long-range PCR to minimize the co-amplification of nuclear mitochondrial DNA segments (NUMTs), PCR-free library preparation to reduce amplification bias, and high-coverage Illumina MiSeq sequencing to produce an average per-sample read depth of 1000 × for low-frequency (5%) variant detection. Point heteroplasmies below 10% frequency were confirmed through replicate amplification, and length heteroplasmy was quantitatively assessed using a custom read count analysis tool. Data analysis involved a redundant, dual-analyst review to minimize errors in haplotype reporting with additional QC checks performed by EMPOP. Applying these methods, eight sample sets were processed from five U.S. metapopulations (African American, Caucasian, Hispanic, Asian American, and Native American) corresponding to self-reported identity at the time of sample collection. Population analyses (e.g., haplotype frequencies, random match probabilities, and genetic distance estimates) were performed to evaluate the eight datasets, with over 95% of haplotypes unique per dataset. The platinum-quality mitogenome haplotypes presented in this study will enable forensic statistical calculations and thereby support the usage of mitogenome sequencing in forensic laboratories.
Agrobacterium tumefaciens-Mediated Genetic Transformation of the Ect-endomycorrhizal Fungus Terfezia boudieri
Authors: Satish Lakkakula , Kamle Madhu , Keren Guy , Patil Chandrashekhar D. , Yehezkel Galit , Barak Ze’ev , Kagan-Zur Varda , Kushmaro Ariel , Sitrit Yaron
Published: October 2020

Mycorrhizal desert truffles such as Terfezia boudieri, Tirmania nivea, and Terfezia claveryi, form mycorrhizal associations with plants of the Cistaceae family. These valued truffles are still collected from the wild and not cultivated under intensive farming due to the lack of basic knowledge about their biology at all levels. Recently, several genomes of desert truffles have been decoded, enabling researchers to attempt genetic manipulations to enable cultivation. To execute such manipulations, the development of molecular tools for genes transformation into truffles is needed. We developed an Agrobacterium tumefaciens-mediated genetic transformation system in T. boudieri. This system was optimized for the developmental stage of the mycelia explants, bacterial optical density, infection and co-cultivation durations, and concentrations of the selection antibiotics. The pFPL-Rh plasmid harboring hph gene conferring hygromycin resistance as a selection marker and the red fluorescent protein gene were used as visual reporters. The optimal conditions were incubation with 200 μM of acetosyringone, attaining a bacterial optical density of 0.3 OD600; transfer time of 45 min; and co-cultivation for 3 days. This is the first report on a transformation system for T. boudieri, and the proposed protocol can be adapted for the transformation of other important desert truffles as well as ectomycorrhizal species.
Changes and Variations in Death Due to Senility in Japan
Authors: Bando Masaki , Miyatake Nobuyuki , Kataoka Hiroaki , Kinoshita Hiroshi , Tanaka Naoko , Suzuki Hiromi , Katayama Akihiko
Published: October 2020

Objective: The proportion of elderly individuals (≥65 years old) in Japan has markedly increased. However, the definition of senility in Japan is controversial. The aim of the present study was to investigate changes and variations in the number of deaths due to senility in Japan. Methods: Information on the number of deaths due to senility between 1995 and 2018 as well as other major causes of death was obtained from the Statistics Bureau of Japan official website. Changes and variations in the number of deaths due to senility were compared with other major causes of death in Japan. The relationships between the number of deaths due to senility and socioeconomic factors were also examined in an ecological study. Results: The number of deaths due to senility was 35.7 ± 23.2/one hundred thousand people/year during the observation period and has continued to increase. A change point was identified in 2004 by a Jointpoint regression analysis. Variations in the number of deaths due to senility, which were evaluated by a coefficient of variation, were significantly greater than those due to other major causes of death, i.e., malignant neoplasm, heart diseases, cerebrovascular diseases, and pneumonia. The number of elderly individuals (≥65 years old) (%) and medical bills per elderly subject (≥75 years old) correlated with the number of deaths due to senility. Conclusion: The number of deaths due to senility has been increasing, particularly since 2004. However, variations in the number of deaths due to senility were observed among all prefectures in Japan.
Characteristics Related to Choice of Obstetrician-Gynecologist among Women of Ethiopian Descent in Israel
Authors: Zigdon Avi , Koren Gideon , Korn Liat
Published: October 2020

Background: Patient satisfaction with the quality of health care services is complex with many known factors impacting upon satisfaction, among them the choice of physician. Previous studies examined characteristics of a woman’s choice of gynecologist, but information regarding reasons for these choices among women of Ethiopian descent is lacking. The objective of this study was to identify characteristics related preference of an obstetrician-gynecologist based on gender among women of Ethiopian descent. Method: Analysis of anonymous self-reported questionnaire distributed to 500 women of Ethiopian descent who visited an obstetrician-gynecologist at least once in the past three years (Mean age 29.5; SD = 8.2). Trust in physician was examined using the TPS scale; service quality was checked using the SERVQUAL; and the 5Qs model was used to measure patient’s satisfaction of health care. Results: Very religious (84.1%) and religious (53.6%) women of Ethiopian descent were more likely to prefer a female obstetrician-gynecologist compared to traditional (39.3%) or secular (34.4%) women (p < 0.001). Participants had higher probability to prefer a male gynecologist if they had more employment hours (OR = 3.57, 95% CI = 1.72–7.42, p < 0.001), and the responsiveness of the physician was less important to them (OR = 0.77, 95% CI = 0.60–0.99, p < 0.05). Age of participants, country of birth, years in Israel, family status, being a mother, education or health status were not associated with choosing a female obstetrician-gynecologist. Religious women would prefer to wait longer for a female gynecologist due to modesty imperatives, even at the cost of compromising their health as a result of waiting longer. Conclusions: The findings of this research highlight the importance of accessibility to female obstetrician-gynecologists for women of Ethiopian descent and demonstrate that determinants in the host population rather than immigrant’s past culture, affect the women’s decision. This study demonstrates the importance of the health care system in Israel to enable more female obstetrician-gynecologists to treat women of Ethiopian descent.
Publisher’s Note: Continued Publication of Infectious Disease Reports by MDPI
Authors: Vazquez Franck , Lin Shu-Kun , Vicario Unai
Published: October 2020

Infectious Disease Reports was launched in 2009 and it has been published over the past eleven years by PAGEPress Publications [...]
Discovering Correlations between the COVID-19 Epidemic Spread and Climate
Authors: Lin Shaofu , Fu Yu , Jia Xiaofeng , Ding Shimin , Wu Yongxing , Huang Zhou
Published: October 2020

The outbreak of Corona Virus Disease 2019 (COVID-19) has affected the lives of people all over the world. It is particularly urgent and important to analyze the epidemic spreading law and support the implementation of epidemic prevention measures. It is found that there is a moderate to high correlations between the number of newly diagnosed cases per day and temperature and relative humidity in countries with more than 10,000 confirmed cases worldwide. In this paper, the correlation between temperature/relative humidity and the number of newly diagnosed cases is obvious. Governments can adjust the epidemic prevention measures according to climate change, which will more effectively control the spread of COVID-19.
Nitrogen Removal Efficiency for Pharmaceutical Wastewater with a Single-Stage Anaerobic Ammonium Oxidation Process
Authors: Zuo Lushen , Yao Hong , Li Huayu , Fan Liru , Jia Fangxu
Published: October 2020

A single-stage anaerobic ammonium oxidation (ANAMMOX) process with an integrated biofilm–activated sludge system was carried out in a laboratory-scale flow-through reactor (volume = 57.6 L) to treat pharmaceutical wastewater containing chlortetracycline. Partial nitrification was successfully achieved after 48 days of treatment with a nitrite accumulation of 70%. The activity of ammonia oxidizing bacteria (AOB) decreased when the chemical oxygen demand (COD) concentration of the influent was 3000 mg/L. When switching to the single-stage ANAMMOX operation, (T = 32–34 °C, DO = 0.4–0.8 mg/L, pH = 8.0–8.5), the total nitrogen (TN) removal loading rate and efficiency were 1.0 kg/m3/d and 75.2%, respectively, when the ammonium concentration of the influent was 287 ± 146 mg/L for 73 days. The findings of this study imply that single-stage ANAMMOX can achieve high nitrogen removal rates and effectively treat pharmaceutical wastewater with high concentrations of COD (1000 mg/L) and ammonium.
A Review of Selected Studies on the Factors Associated with the Nutrition Status of Children Under the Age of Five Years in South Africa
Authors: Mkhize Mbalenhle , Sibanda Melusi
Published: October 2020

Malnutrition is a considerable contributor to child mortality and morbidity. Child malnutrition further affects the country’s economic development. Child malnutrition in South Africa is persistent, continuing to be an alarming burden. The nutritional status of kids under the age of five years is a critical indicator of the country’s economic condition and health status. An understanding of the influencers of the nutritional status of children can act as a catalyst in combatting all forms of malnutrition. The purpose of this paper was to review selected studies concerning the factors that affect the nutritional status of children in South Africa. Studies were selected from electronic databases, which were PubMed, Google Scholar, Science Direct, Sabinet African Journals, and the University of Zululand library catalog. The keywords that were used to search studies and articles from the selected database were: risk factors, child nutritional status, children under the age of five years, South Africa, malnutrition, underweight, stunted, wasting, and over-nutrition. Studies and surveys published from 2010–2019 that reported on the factors influencing the nutritional status of children under the age of five years were included in this review. Twenty-seven articles met the inclusion criteria of the study. The 27 articles were made up of 21 cross-sectional articles and six longitudinal articles. The finding from this review highlights that there is a lack of studies conducted in urban areas. The results show that the nutritional status of children is affected by several factors. These include household food insecurity, low household income, illiterate caregivers, unemployment, inadequate dietary intake, low birth weight, consumption of monotonous diets, poor caregiver’s nutritional knowledge, poor access to water and sanitation, poor weaning practices, age of the caregiver, and demographic characteristics of a child (age and gender). It is critical to have an understanding of the factors that affect the nutritional status of children. Such knowledge can significantly contribute to formulating policies that can enhance nutrition security and the country’s economy. Moreover, insights into strategic interventions to eradicate all forms of malnutrition can be made.
Prevalence and Risk Factors Associated with Malaria among Children Aged Six Months to 14 Years Old in Rwanda: Evidence from 2017 Rwanda Malaria Indicator Survey
Authors: Habyarimana Faustin , Ramroop Shaun
Published: October 2020

Malaria is a major public health risk in Rwanda where children and pregnant women are most vulnerable. This infectious disease remains the main cause of morbidity and mortality among children in Rwanda. The main objectives of this study were to assess the prevalence of malaria among children aged six months to 14 years old in Rwanda and to identify the factors associated with malaria in this age group. This study used data from the 2017 Rwanda Malaria Indicator Survey. Due to the complex design used in sampling, a survey logistic regression model was used to fit the data and the outcome variable was the presence or absence of malaria. This study considered 8209 children in the analysis and the prevalence of malaria was 14.0%. This rate was higher among children aged 5–9 years old (15.6%), compared to other age groups. Evidently, the prevalence of malaria was also higher among children from poor families (19.4%) compared to children from the richest families (4.3%). The prevalence of malaria was higher among children from rural households (16.2%) compared to children from urban households (3.4%). The results revealed that other significant factors associated with malaria were: the gender of the child, the number of household members, whether the household had mosquito bed nets for sleeping, whether the dwelling had undergone indoor residual spraying in the 12 months prior to the survey, the location of the household’s source of drinking water, the main wall materials of the dwelling, and the age of the head of the household. The prevalence of malaria was also high among children living in houses with walls built from poorly suited materials; this suggests the need for intervention in construction materials. Further, it was found that the Eastern Province also needs special consideration in malaria control due to the higher prevalence of the disease among its residents, compared to those in other provinces.
Physical Activity and Psychosocial Characteristics of the Peer Supporters in the PLAN-A Study—A Latent Class Analysis
Authors: Salway Ruth , Sebire Simon J. , Tibbitts Byron , Sanderson Emily , Kandiyali Rebecca , Willis Kate , MacNeill Stephanie J. , Jago Russell
Published: October 2020

PLAN-A is a cluster randomised controlled trial of a peer-led physical activity intervention which uses peer supporters to increase the physical activity of 13–14-year-old girls in the UK. This paper uses latent class analysis to identify classes in the whole study population and investigate how those selected as peer supporters in PLAN-A were drawn from different social groups. We identified five classes of girls, based on psychosocial variables (self-esteem, physical activity self-efficacy, motivation, physical activity values among friends and peer support for physical activity (PA) and physical activity behaviour variables (average minutes of weekday MVPA, sedentary time and screen viewing). Peer supporters were similar to the whole study population in terms of overall demographics, but were drawn unequally from the five classes. In addition, there was considerable variation in the distribution of peer supporters between schools. The selection of peer supporters is an integral component of peer-led interventions and should be explored and linked to underlying theory to understand the characteristics of those recruited. However, demographic representativeness is not necessarily the aim, and simple reporting of overall demographic comparisons may mask important differences within subgroups.
Preparedness and Responses Faced during the COVID-19 Pandemic in Belgium: An Observational Study and Using the National Open Data
Authors: He Rongxin , Zhang Jun , Mao Ying , Degomme Olivier , Zhang Wei-Hong
Published: October 2020

This study aimed to descript the Belgian COVID-19 responses process according to the WHO’s (World Health Organization) Health Emergency and Disaster Risk Management Framework (Health EDRM Framework) and to present the measures taken and epidemic impact in the different phases of COVID-19 in Belgium. The WHO’s EDRM Framework was used for reviewing the Belgian Public health emergency preparedness and responses in the context of COVID-19. Information on the measures taken was collected through the literature review including all government’s communication, reports, and scientific papers. All epidemic data were extracted from a national open database managed and published by the Sciensano. Additionally, two authors closely followed the Belgian situation since the beginning of the pandemic and updated the data every day. During the COVID-19 pandemic, the anti-epidemic strategy was mainly to avoid medical resources exceeding the upper limit. Belgium issued a series of emergency decrees to limit the spread of the virus. An existing structure of “federal-region-municipal” as the framework of public health emergency preparedness and response was adapted. The emergency response process in Belgium was divided into four phases: information-evaluation-coordination-decision-making at the region level and the final decision-making at the federal level. Belgium also implemented a phased plan in the process of setting up and lifting the lockdown. However, it was vulnerable in early response, due to the shortage of medical equipment supplies in general, and more particularly for the long term care facilities (LTCFs). Belgium has achieved an intensive cooperation between stakeholders based on an existing multisectoral emergency organization framework. Legislation, medical insurance, and good communication also played a role in limiting the spread of viruses. However, the authorities underestimated the risk of an epidemic and did not take quarantine measures among people suspected affected by SARS-COV-2 in the early stages, resulting in insufficient medical equipment supply and a large number of deaths in the LTCF. The implementation of the lockdown measure in Belgium also encountered obstacles. The lockdown and its exit strategy were both closely related to the pandemic situation and social and economic life. The authorities should strengthen information management, improve the public awareness of the measures, and find out the balance points between the social and economic life and infection control measures.
Community Based Interventions for Problematic Substance Use in Later Life: A Systematic Review of Evaluated Studies and Their Outcomes
Authors: Hafford-Letchfield Trish , McQuarrie Tricia , Clancy Carmel , Thom Betsy , Jain Briony
Published: October 2020

Problematic substance use (PSU) in later life is a growing global problem of significant concern in tandem with a rapidly ageing global population. Prevention and interventions specifically designed for older people are not common, and those designed for mixed-age groups may fail to address the unique and sometimes complex needs of ageing communities. We report findings from a systematic review of the empirical evidence from studies which formally evaluated interventions used with older people and reported their outcomes. Nineteen studies were included, of which thirteen focused solely on alcohol-related problems. Eight interventions utilised different types of screening, brief advice and education. The remaining drew on behavioural, narrative and integrated or multi-disciplinary approaches, which aimed to meet older people’s needs holistically. Quality assessment of study design helped to review evaluation practice. Findings point to recommendations for sustainable and well-designed intervention strategies for PSU in later life, which purposefully align with other areas of health and well-being and are delivered in locations where older people normally seek, or receive, help. There is further scope for engagement with older people’s own perspectives on their needs and help-seeking behaviours. Economic evaluation of the outcome of interventions would also be useful to establish the value of investing in targeted services to this underserved population.
Facilitators and Barriers in the Organ Donation Process: A Qualitative Study among Nurse Transplant Coordinators
Authors: Fernández-Alonso Víctor , Palacios-Ceña Domingo , Silva-Martín Celia , García-Pozo Ana
Published: October 2020

Background: Spain is the world leader in organ donation, with a rate of 49.0 donations per million population. Nurse transplant coordinators fulfill key roles for the success of the complex donation process. Our aims were: (a) to describe the experience of nurse transplant coordinators and (b) to identify barriers and facilitators during the process of organ donation. Methods: A qualitative phenomenological study was conducted within the National Transplant Organization. A purposive sampling method was used, and data collection methods included semistructured interviews, researcher field notes, and participants’ personal letters. A systematic text condensation analysis was performed. The study was approved by the Clinical Research Ethics Committee. Results: A total of 16 participants were recruited and four themes were identified: (a) a different job for nurses, (b) facilitators and barriers of the coordinator’s job, (c) not a job for a novice nurse, and (d) coordinators facing a paradigm shift. Coordinators described their job as being characterized with uncertainty and having to face emotional and institutional barriers. The facilitators identified were high educational level and training, and feelings of pride for being part of the National Transplant Organization. Conclusions: The organ donation process requires specialized training to avoid organizational barriers.
Effects of Task-Specific and Strength Training on Simulated Military Task Performance in Soldiers
Authors: Ojanen Tommi , Häkkinen Keijo , Hanhikoski Jaakko , Kyröläinen Heikki
Published: October 2020

A soldier’s occupational physical task requirements are diverse and varied. However, the type of physical training that most effectively improves soldiers’ occupational task requirements has not been studied previously. The purpose of this study was to determine the important strength characteristics for soldiers during a repeated simulated military task course, and the type of training that may be effective to improve these abilities during a specialized military training period. Forty-two (n = 42) soldiers participated in the study. They were divided into three training groups; a soldier task-specific training group (TSG, n = 17), a strength training group (STG, n = 15), and a control group (CON, n = 10). Participants were measured before (PRE), middle (MID) and after (POST) the 12-week training intervention for strength performance and simulated military task test. Simulated military task performance improved significantly in TSG and STG between the PRE and MID measurements (from 9.4 to 15.7%). TSG and STG improved in various spilt times, especially in strength tasks; casualty drag (from 8.3 to 13.6%) and kettlebell carry (from 13.2 to 22.4%) between the PRE and MID measurements. The present study showed that both the training of TSG and STG were more effective than the training of CON (control group) in terms of improving the performance in the repeated simulated military task course. The present study showed that training of TSG was as effective as STG to improve repeated simulated military task course time. Therefore, an optimal training combination should include high-intensity simulated military task field training and strength training programmed with consideration of the military training phase and environmental possibilities.
A Systematic Review of the Value Assessment Frameworks Used within Health Technology Assessment of Omics Technologies and Their Actual Adoption from HTA Agencies
Authors: Hoxhaj Ilda , Govaerts Laurenz , Simoens Steven , Van Dyck Walter , Huys Isabelle , Gutiérrez-Ibarluzea Iñaki , Boccia Stefania
Published: October 2020

Background: Omics technologies, enabling the measurements of genes (genomics), mRNA (transcriptomics), proteins (proteomics) and metabolites (metabolomics), are valuable tools for personalized decision-making. We aimed to identify the existing value assessment frameworks used by health technology assessment (HTA) doers for the evaluation of omics technologies through a systematic review. Methods: PubMed, Scopus, Embase and Web of Science databases were searched to retrieve potential eligible articles published until 31 May 2020 in English. Additionally, through a desk research in HTA agencies’ repositories, we retrieved the published reports on the practical use of these frameworks. Results: Twenty-three articles were included in the systematic review. Twenty-two frameworks, which addressed genetic and/or genomic technologies, were described. Most of them derived from the ACCE framework and evaluated the domains of analytical validity, clinical validity and clinical utility. We retrieved forty-five reports, which mainly addressed the commercial transcriptomic prognostics and next generation sequencing, and evaluated clinical effectiveness, economic aspects, and description and technical characteristics. Conclusions: A value assessment framework for the HTA evaluation of omics technologies is not standardized and accepted, yet. Our work reports that the most evaluated domains are analytical validity, clinical validity and clinical utility and economic aspects.
Study of the Relationship between the Average Annual Temperature of Atmospheric Air and the Number of Tick-Bitten Humans in the North of European Russia
Authors: Tronin Andrei , Tokarevich Nikolay , Blinova Olga , Gnativ Bogdan , Buzinov Roman , Sokolova Olga , Evengard Birgitta , Pahomova Tatyana , Bubnova Liliya , Safonova Olga
Published: October 2020

In recent decades, a considerable increase in the number of tick-bitten humans has been recorded in the north of European Russia. At the same time, significant climatic changes, such as an increase in air temperature, were noticed in this region. The northern border of the ixodidae distribution area lies in the north of European Russia, therefore the analysis of the population dynamics is of particular interest regarding the possible impact of the climate changes. Unfortunately, in such a large territory field, studies on tick abundance are very difficult. In our study, the official statistics for the number of tick-bitten humans were used. This kind of statistical analysis has been conducted in the Russian Federation for many years, and can be used for the estimation of climate change impact on tick abundance. Statistical data on tick-bitten humans have been collected in three large regions for several decades. For the same regions, the average annual air temperature was calculated and modeled. An S-shaped distribution of the number of victims depending on the average annual air temperature was established, which can be described as “Verhulst’s law”, or logistic function. However, the development of the population does not depend on time, but on the temperature of the ambient air.
Importance of Deubiquitination in Macrophage-Mediated Viral Response and Inflammation
Authors: Rasaei Roya , Sarodaya Neha , Kim Kye-Seong , Ramakrishna Suresh , Hong Seok-Ho
Published: October 2020

Ubiquitination and deubiquitination play a fundamental role in the signaling pathways associated with innate and adaptive immune responses. Macrophages are key sentinels for the host defense, triggering antiviral and inflammatory responses against various invading pathogens. Macrophages recognize the genetic material of these pathogens as pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) through the activation of its pattern recognition receptors (PRRs), initiating the cascade of immune signaling, which leads to the production of pro- and anti-inflammatory cytokines that initiates the appropriate immune response. Macrophage-mediated immune response is highly regulated and tightly controlled by the ubiquitin system since its abnormal activation or dysregulation may result in the severe pathogenesis of numerous inflammatory and autoimmune diseases. Deubiquitinating enzymes (DUBs) play a crucial role in reversing the ubiquitination and controlling the magnitude of the immune response. During infection, pathogens manipulate the host defense system by regulating DUBs to obtain nutrients and increase proliferation. Indeed, the regulation of DUBs by small molecule inhibitors has been proposed as an excellent way to control aberrant activation of immune signaling molecules. This review is focused on the complex role of DUBs in macrophage-mediated immune response, exploring the potential use of DUBs as therapeutic targets in autoimmune and inflammatory diseases by virtue of small molecule DUB inhibitors.
Evaluation of Sterilization/Disinfection Methods of Fibrous Polyurethane Scaffolds Designed for Tissue Engineering Applications
Authors: Łopianiak Iwona , Butruk-Raszeja Beata A.
Published: October 2020

Sterilization of a material carries the risk of unwanted changes in physical and chemical structure. The choice of method is a challenge—the process must be efficient, without significantly changing the properties of the material. In the presented studies, we analyzed the effect of selected sterilization/disinfection techniques on the properties of nanofibrous polyurethane biomaterial. Both radiation techniques (UV, gamma, e-beam) and 20 minutes’ contact with 70% EtOH were shown not to achieve 100% sterilization efficiency. The agar diffusion test showed higher sterilization efficiency when using an antimicrobial solution (AMS). At the same time, none of the analyzed techniques significantly altered the morphology and distribution of fiber diameters. EtOH and e-beam sterilization resulted in a significant reduction in material porosity together with an increase in the Young’s modulus. Similarly, AMS sterilization increased the value of Young’s modulus. In most cases, the viability of cells cultured in contact with the sterilized materials was not affected by the sterilization process. Only for UV sterilization, cell viability was significantly lower and reached about 70% of control after 72 h of culture.
Sexual Dimorphism in the Chemical Composition of Male and Female in the Dioecious Tree, Juniperus communis L., Growing under Different Nutritional Conditions
Authors: Rabska Mariola , Pers-Kamczyc Emilia , Żytkowiak Roma , Adamczyk Dawid , Iszkuło Grzegorz
Published: October 2020

We hypothesized that female and male individuals of the dioecious tree species, Juniperus communis, exhibit different strategies of resource allocation when growing under stress conditions. To test this hypothesis, we performed a two-year pot experiment on plants exposed to different levels of nutrient availability. Analysis of the plants revealed a higher concentration of carbohydrates, carbon, and phenolic compounds in needles of female plants, indicating that females allocate more resources to storage and defense than males. This difference was independent of nutrient availability. Differences in carbohydrates levels between the sexes were most often significant in June, during the most intensive phase of vegetative growth in both sexes, but could also be attributed to female resources investment in cone development. A higher level of nitrogen and other macroelements was observed in males than in females, which may have been connected to the accumulation of resources (nitrogen) for pollen grain production in males or greater allocation of these elements to seeds and cones in females. The interaction between sex and soil fertilization for the C:N ratio may also indicate sex-specific patterns of resource allocation and utilization, which is impacted by their availability during specific periods of J. communis annual life cycle.
The Study of Zinc Ions Binding to αS1-, β- and κ-Casein
Authors: Rodzik Agnieszka , Pomastowski Paweł , Railean-Plugaru Viorica , Sprynskyy Myroslav , Buszewski Bogusław
Published: October 2020

The presented studies focused on the specificity binding of particular casein fractions: αS1-, β- and κ-casein (αS1CN, βCN, κCN), with zinc ions. The binding mechanism was determined by kinetic modeling using results of batch sorption. For this goal, models of zero-order kinetics, pseudo-first-order, pseudo-second-order and Weber–Morris intraparticle diffusion were used. The formation of Zn-αS1CN, Zn-βCN and Zn-κCN complexes was additionally monitored using spectroscopic methods such as Fourier transform infrared spectroscopy (FT-IR) and Raman spectroscopy, characterizing active functional groups involved in the binding process. Additionally, a mass spectrometry technique—matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)—was used to characterize respective protein fractions and obtained complexes. Spectroscopic and spectrometric studies were carried out both before and after binding the protein with zinc ions. The obtained results showed the difference in Zn-αS1CN, Zn-βCN and Zn-κCN complexes created at separate kinetic stages. On the basis of instrumental studies, a significant influence of acidic (glutamic acid (Glu), aspartic acid (Asp)) and aromatic (tryptophan (Trp), phenylalanine (Phe), tyrosine (Tyr)) amino acids on the formation of metal complexes was proven. In turn, spectrometric studies allowed determining the molecular masses of casein isoforms before and after binding to zinc ions.
Aging-Affected MSC Functions and Severity of Periodontal Tissue Destruction in a Ligature-Induced Mouse Periodontitis Model
Authors: Aung Kyaw Thu , Akiyama Kentaro , Kunitomo Masayoshi , Mun Aung Ye , Tosa Ikue , Nguyen Ha Thi Thu , Zhang Jiewen , Kohno Teisaku , Ono Mitsuaki , Hara Emilio Satoshi , Kuboki Takuo
Published: October 2020

Mesenchymal stem cells (MSCs) are known to play important roles in the repair of lost or damaged tissues and immunotolerance. On the other hand, aging is known to impair MSC function. However, little is currently known about how aged MSCs affect the host response to the local inflammatory condition and tissue deterioration in periodontitis, which is a progressive destructive disease of the periodontal tissue potentially leading to multiple tooth loss. In this study, we examined the relationship between aging-induced impairment of MSC function and the severity of periodontal tissue destruction associated with the decrease in host immunomodulatory response using a ligature-induced periodontitis model in young and aged mice. The results of micro computerized tomography (micro-CT) and histological analysis revealed a more severe bone loss associated with increased osteoclast activity in aged (50-week-old) mice compared to young (5-week-old) mice. Immunostaining analysis revealed that, in aged mice, the accumulation of inflammatory T and B cells was higher, whereas the percentage of platelet-derived growth factor receptor α (PDGFRα)+ MSCs, which are known to modulate the apoptosis of T cells, was significantly lower than in young mice. In vitro analysis of MSC function showed that the expression of surface antigen markers for MSCs (Sca-1, CD90, CD146), colony formation, migration, and osteogenic differentiation of aged MSCs were significantly declined compared to those of young MSCs. Moreover, a significantly higher proportion of aged MSCs were positive for the senescence-associated β galactosidase activity. Importantly, aged MSCs presented a decreased expression of FAS-L, which was associated with a lower immunomodulatory property of aged MSCs to induce T cell apoptosis in co-cultures compared with young MSCs. In summary, this is the first study showing that aging-induced impairment of MSC function, including immunomodulatory response, is potentially correlated with progressive periodontal tissue deterioration.
Structural Insights into β-arrestin/CB1 Receptor Interaction: NMR and CD Studies on Model Peptides
Authors: Morales Paula , Bruix Marta , Jiménez M. Angeles
Published: October 2020

Activation of the cannabinoid CB1 receptor induces different cellular signaling cascades through coupling to different effector proteins (G-proteins and β-arrestins), triggering numerous therapeutic effects. Conformational changes and rearrangements at the intracellular domain of this GPCR receptor that accompany ligand binding dictate the signaling pathways. The GPCR-binding interface for G proteins has been extensively studied, whereas β-arrestin/GPCR complexes are still poorly understood. To gain knowledge in this direction, we designed peptides that mimic the motifs involved in the putative interacting region: β-arrestin1 finger loop and the transmembrane helix 7-helix 8 (TMH7-H8) elbow located at the intracellular side of the CB1 receptor. According to circular dichroism and NMR data, these peptides form a native-like, helical conformation and interact with each other in aqueous solution, in the presence of trifluoroethanol, and using zwitterionic detergent micelles as membrane mimics. These results increase our understanding of the binding mode of β-arrestin and CB1 receptor and validate minimalist approaches to structurally comprehend complex protein systems.
Redox Regulation by Protein S-Glutathionylation: From Molecular Mechanisms to Implications in Health and Disease
Authors: Musaogullari Aysenur , Chai Yuh-Cherng
Published: October 2020

S-glutathionylation, the post-translational modification forming mixed disulfides between protein reactive thiols and glutathione, regulates redox-based signaling events in the cell and serves as a protective mechanism against oxidative damage. S-glutathionylation alters protein function, interactions, and localization across physiological processes, and its aberrant function is implicated in various human diseases. In this review, we discuss the current understanding of the molecular mechanisms of S-glutathionylation and describe the changing levels of expression of S-glutathionylation in the context of aging, cancer, cardiovascular, and liver diseases.
Fluid Shear Stress Induces EMT of Circulating Tumor Cells via JNK Signaling in Favor of Their Survival during Hematogenous Dissemination
Authors: Xin Ying , Li Keming , Yang Mo , Tan Youhua
Published: October 2020

Tumor cells metastasize to distal organs mainly through hematogenous dissemination, where they experience considerable levels of fluid shear stress. Epithelial–mesenchymal transition (EMT) plays a critical role in tumor metastasis. However, how fluid shear stress influences the EMT phenotype of circulating tumor cells (CTCs) in suspension has not been fully understood. The role of shear-induced EMT in cell survival under blood shear flow remains unclear. This study shows that the majority of breast CTCs underwent apoptosis under shear flow and the surviving cells exhibited mesenchymal phenotype, suggesting that fluid shear stress induces EMT. Mechanistically, fluid shear stress-activated Jun N-terminal kinase (JNK) signaling, inhibition/activation of which suppressed/promoted the EMT phenotype. In particular, shear flow facilitated the JNK-dependent transition of epithelial CTCs into the mesenchymal status and maintained the pre-existing mesenchymal cells. Importantly, the induction of EMT suppressed the pro-apoptosis gene p53 upregulated modulator of apoptosis (PUMA) and enhanced the survival of suspended CTCs in fluid shear stress, which was rescued by overexpressing PUMA or silencing JNK signaling, suggesting that shear-induced EMT promotes CTC survival through PUMA downregulation and JNK activation. Further, the expressions of EMT markers and JUN were correlated with poor patient survival. In summary, our findings have demonstrated that fluid shear stress induces EMT in suspended CTCs via JNK signaling that promotes their survival in shear flow. This study thus unveils a new role of blood shear stress in CTC survival and facilitates the development of novel therapeutics against tumor metastasis.
The Emerging Role of LHb CaMKII in the Comorbidity of Depressive and Alcohol Use Disorders
Authors: Shor Chaya , Zuo Wanhong , Eloy Jean D. , Ye Jiang-Hong
Published: October 2020

Depressive disorders and alcohol use disorders are widespread among the general population and are significant public health and economic burdens. Alcohol use disorders often co-occur with other psychiatric conditions and this dual diagnosis is called comorbidity. Depressive disorders invariably contribute to the development and worsening of alcohol use disorders, and vice versa. The mechanisms underlying these disorders and their comorbidities remain unclear. Recently, interest in the lateral habenula, a small epithalamic brain structure, has increased because it becomes hyperactive in depression and alcohol use disorders, and can inhibit dopamine and serotonin neurons in the midbrain reward center, the hypofunction of which is believed to be a critical contributor to the etiology of depressive disorders and alcohol use disorders as well as their comorbidities. Additionally, calcium/calmodulin-dependent protein kinase II (CaMKII) in the lateral habenula has emerged as a critical player in the etiology of these comorbidities. This review analyzes the interplay of CaMKII signaling in the lateral habenula associated with depressive disorders and alcohol use disorders, in addition to the often-comorbid nature of these disorders. Although most of the CaMKII signaling pathway’s core components have been discovered, much remains to be learned about the biochemical events that propagate and link between depression and alcohol abuse. As the field rapidly advances, it is expected that further understanding of the pathology involved will allow for targeted treatments.
MYC Targets Scores Are Associated with Cancer Aggressiveness and Poor Survival in ER-Positive Primary and Metastatic Breast Cancer
Authors: Schulze Amy , Oshi Masanori , Endo Itaru , Takabe Kazuaki
Published: October 2020

MYC is one of the most studied oncogenes that is known to promote cell proliferation. We utilized MYC targets v1 and MYC targets v2 scores of gene set variation analysis and hypothesized that these scores correlate with tumor aggressiveness and survival outcomes. We examined a total of 3109 breast cancer patients from TCGA, METABRIC, and GSE124647 cohorts. In each cohort, the patients were divided into high- and low-score groups using the upper third value as the cut off. As expected, higher scores were related to increased cell proliferation and worse clinical and pathologic features. High MYC targets scores were associated with worse survival, specifically in primary ER-positive breast cancer, consistently in both TCGA and METABRIC cohorts. In ER-positive breast cancer, high MYC targets v1, but not v2 score, was associated with high mutation load, and high MYC targets v1 and v2 scores were both associated with increased infiltration of pro- and anti-cancerous immune cells. We found that high MYC scores were associated with worse survival in metastatic breast cancer. Our findings show that the MYC targets v1 and v2 scores are associated with tumor aggressiveness and poor prognosis in ER-positive primary tumors, as well as in metastatic breast cancer.