bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Support among Elderly in Institutions: Towards Healthy Aging (Sokongan Sosial dalam Kalangan Warga Emas di Institusi: Ke Arah Penuaan Sihat)
Authors: Ibrahim Nabisah
Published: March 2021

This paper aims to discuss the importance of social support in developing healthy aging among elderly in institutions. It covers a discussion on the factors that are required to define the availability of social support for the elderly and what kinds of support systems needed in order to maintain healthy aging. Realizing about the limitation of support system available for elderly in institutions, this paper also includes the discussion on factors that inhibits social support among this marginal group and provides strategies and intervention on how to enhance the availability of social support for this population.
Plant residues, beneficial microbes and integrated phosphorus management for improving hybrid maize (Zea mays L.) growth and total biomass
Authors: Amanullah Amanullah , Iqbal Asif , Muhammad Asim , Altawaha Abdel Rahman , Shah Azizullah , Parmar Brajendra
Published: March 2021

Phosphorus (P) unavailability and lack of organic matter in calcareous soils in semiarid climates are the major reasons for low crop productivity. This field experiment was conducted at the Agronomy Research Farm of The University of Agriculture Peshawar, during the summer of 2015 to investigate the impact of plant residues (PR) (faba bean, garlic and paper mulberry residues) and phosphorous sources [(60 and 120kg ha-1) from single super phosphate (SSP) and poultry manure (PM)] with (+) and without (-) phosphate solubilizing bacteria (PSB) on the phenological development, growth and biomass yield of hybrid maize “CS-200”. Among the PR, application of faba bean residue was found to delay phenological development (days to tasseling, silking and physiological maturity), improved growth (taller plants, higher leaf area per plant and leaf area index) and produced the highest biomass yield (faba bean>garlic>paper mulberry residues). Application of P at the rate of 120kg ha-1 from the inorganic source (SSP) was more beneficial in terms of better growth and higher biomass yield (120-SSP≥120-PM>60-SSP>60-PM kg P ha-1). The plots with (+) PSB showed enhanced phenological development, produced significantly taller plants with higher leaf area per plant and leaf area index and produced the highest biomass yield. On the basis of these results we concluded that the application of faba bean residues, phosphorus at the rate of 120kg ha-1 either from organic or inorganic sources with the inoculation of seed with PSB improved the growth and total biomass of hybrid maize in the study area.
Community Participation in Public Peace and Order in Imandi Village, East Dumoga Subdistrict, Bolaang Mongondow Regency
Authors: Mantiri Jeane , Siwi Cynthia Maria
Published: March 2021

This study aims to analyze and describe the public participation level and the factors supporting and inhibiting public participation in maintaining peace and order in Imandi Village. This research uses a descriptive qualitative research method. This research was located in Imandi Village, East Dumoga Subdistrict, Bolaang Mongondow Regency, North Sulawesi Province, Indonesia. The results showed that: 1) The Imandi Village community’s participation is still not well implemented. Therefore, it will be better to maintain public peace and order in the village if it starts from individuals as small community units. It allows the realization of solidarity, which will significantly affect group members or community members in public peace and order implementation. 2) Efforts to motivate people to participate through Mapalus (mutual assistance activities) need leaders who can be role models. Village community leaders can be the key motivator in mutual assistance activities, but the government’s participation is required. (3) The village government and its apparatus must continue to managing and fostering community members, especially in multicultural communities, to prevent the disruption of public peace and order.
Development of Children's Literature Reading Materials to Support SDN 028228 Binjai Student Literacy Activities
Authors: Br Ginting Meta Melisa , Solin Mutsyuhito , Hadi Wisman
Published: March 2021

This research is motivated by the lack of availability of reading materials for children's literature, reading materials that are not suitable for the age of growth and development of children's psychology, then students have an interest in reading, and reading habits are not yet entrenched, so it is necessary to develop varied reading materials and support students in activities. literacy. Children's literature reading materials are needed at SDN 028228 Binjai to support students' literacy activities. This study aims to determine the results of the development of children's literature reading materials in the form of comics to support literacy activities of SDN 028228 Binjai students. The research method used was research and development (Research and Development) by Borg and Gall. The results showed that (1) The reading material development process was carried out in several stages, namely preliminary studies, initial product development and product testing. (2) The results of the reading material feasibility test show that (a) the result of the material expert's validation on the reading material as a whole is 83.3% with the criteria of "very good". (b) the results of the validation by design experts on the reading material as a whole obtained data 88.3% with "very good" criteria. (c) the results of the overall classroom teacher assessment of the reading material obtained an average of 91% with the criteria "very good" (3) The results of the effectiveness of the development of reading materials show that (a) the results of individual trials on reading materials obtained an average of 79.6% with the criteria "good ", The results of small group trials on reading materials obtained an average of 88.2% with the criteria" very good ", limited field test results on reading materials obtained an average of 90.1% with the criteria" very good ". (b) the results of the quality of using children's literature in the form of comics to support students' literacy activities were obtained an average of 88.65% (posttest), while before the use of children's literature in the form of comics, the average was 68.40% (pretest). The difference in value is 20.25% which means that children's literature reading material in the form of comics can improve the results of students' literacy activities from before. The implications of this research are (1) children's literary reading materials to support students 'literacy activities can increase students' knowledge of North Sumatra folklore; (2) the results of this study can enrich the treasury of science in order to increase creativity in the development of reading materials, especially those related to the development of children's literature reading materials in North Sumatra.
Consumerist Approach to Sexuality in A World of Dynamism: Hanif Kureishi’s The Nothing
Authors: Gulcu Tarik Ziyad
Published: March 2021

As one of the major phenomena in the contemporary global context, consumerism has been shaping lifestyles in different aspects. Signifying the demand for the consumption of the properties that are produced and accessed quickly, consumerism has not only shaped the tendencies for the consumption of products, but it has also had impact on the approach to interpersonal relations in cultural, social and individual areas. In contemporary British fiction, Kamila Shamsie focuses on the disillusionment of the immigrants with their hopes for a civilised life due to their consideration as “outsiders” and she views this as an embodiment of the consumption of their dreams for the future in Home Fire (2017). Zadie Smith reflects the consumerist approach to the relations among family members in On Beauty (2005) with reference to Howard Belsey’s affair with Victoria as a signification of the quest for his new self and his failed efforts for the reconciliation with his family. However, in The Nothing (2017), Kureishi reveals that consumerism also leads to temporary sexual relations among the people. Focusing on Zee’s affair with Eddie instead of her husband, Waldo because of his old age and infertility, Eddie’s sexual relations with Patricia and Sarah, Kureishi’s The Nothing invites reading in relation to its focus on the short-term sexual relations among the people as an embodiment of the consumerist approach to interpersonal relations and an inevitable quest for a new personal identity within the dynamism of the contemporary world.
Brazil Inside Out 2nd edition
Authors: Rocha Jan , McDonagh Francis
Published: March 2021

Brazil stands tall on the world stage as host for the world cup and olympic and paralympic games, attracting millions of new tourists to a country of dazzling scenery and welcoming people. In today's world, it is remarkable for the lack of serious ethnic, religious or racial conflict. Yet Brazil also faces huge challenges: combining economic growth with measures to reduce the huge social inequality inherited from its slave-owning past, respecting ethnic and cultural diversity, ensuring a popular say in government, meeting energy needs while preserving the environment – especially the Amazon rainforest – and adapting to climate change. Now an economic recession has exposed flaws in the economic model and corruption scandals have come close to paralysing the government. Nationwide protests suggest that, despite the new prosperity and measures to redistribute income, the government has not done enough to satisfy the demands of the poor and emerging middle classes. But for all its problems, Brazil is still the country of sun,sea, sand and sex, the exuberance displayed in carnival. This short book provides an introduction to the country for the student and traveller alike, people who want to know more about the real Brazil than is found in an ordinary guidebook.
Palestinian Women’s Organization’s: Their Challenging Journey towards Women’s Empowerment
Authors: Abuiyada Dr. Reem
Published: March 2021

Palestinian Women’s organizations have a very important role in Palestine's civil society. The development of these organizations is well recognized and they reached their peak at the beginning of the INTIFADA.
Until the creation of the Palestinian Authority (PA), women’s organizations formed part of the national struggle against the Israeli occupation, and their agenda was subordinate to that of the national movement. In the late 1980s, however, a process of transformation was initiated that provided women’s organizations with the opportunity to focus on women’s issues. Indeed, since the creation of the PA, women’s organizations have focused almost exclusively on women’s issues.
The PA, in contrast, has attempted to marginalize women, as reflected in the process of its consolidation. As a result, women’s organizations have attempted to influence PA policy to improve the position of women in Palestinian society.
This paper examines the means and strategies that the Palestinian Women’s Organizations have adopted to influence Palestinian Authority (PA) policy.
Periodonal desiease – local antiseptic therapy: problem of efficiency. Literature review
Authors: Khabadze Z. S. , Generalova Y. A. , Shubaeva V. S. , Abdulkerimova S. M. , Bakaev Y. A. , Mordanov O. S.
Published: March 2021

The purpose of this reviewarticle is to analyze the current data on the use of antiseptics in the treatment of periodontitis, development of resistance of periodontopathogens to antiseptic agents using the example of chlorhexidine, cetylpyridinium chloride and hexetidine. Periodontal pathogens are an integral part of the commensal microflora of the oral cavity, but under certain conditions and under the influence of etiological factors, their number begins to progressively grow, which increases the risk of initiation of periodontal diseases through the formation of aggressive biofilm on the teeth.

Materials and methods. Тhe study of publications was produced in the electronic databases such as PubMed and Google Scholar in the course of a systematic review of the literature. Included articles contain information about antiseptic agents which are chlorhexidine, cetylpyridinium chloride and hexetidine, as well as their effect on periodontopathogens and the possibility of developing resistance in them against these antiseptics.

Results. 127 articles were viewed during the review. After analyzing the literature for inclusion criteria, the total number of publications has become 94.

Conclusions. Аccording to the analyzed data, we have found that antiseptic treatment of the oral cavity and lesions in periodontitis is an integral part of the treatment of this inflammatory disease, as an addition to the mechanical treatment protocol. Chlorhexidine in local forms of delivery has shown particular activity against periodontopathogens.
Efektifitas Terapi Oksigen Terhadap Downes Score pada Pasien Asfiksia Neonatus di Ruang Perinatologi
Authors: Nurviyanti Nurviyanti , Suparti Sri
Published: March 2021

Asfiksia merupakan resiko tinggi pada bayi baru lahir yang dapat menyebabkan kematian atau sakit berat. Bayi asfiksia dikelola dengan terapi oksigen untuk menghindari distress pernapasan. Analisis derajat distres pernapasan dapat menggunakan Downes score. Dikatakan baik bila jumlah nilai Downes score semakin kecil atau nol. Tujuan penelitian ini untuk mengetahui efektifitas terapi oksigen terhadap Downes score pada pasien asfiksia neonatus. Jenis penelitian kuantitatif dengan observasi analitik dan pendekatan prospektif. Jumlah sampel sebanyak 25 responden dengan teknik accidental sampling. Instrumen penelitian yang digunakan adalah lembar observasi Downes score. Data dikumpulkan dari bayi asfiksia sedang hingga berat, dengan menilai Downes score pra dan pasca terapi oksigen dan dianlisis  dengan uji Wilcoxon test.  Hasil penelitian menunjukkan jenis asfiksia terbanyak adalah asfiksia sedang (88%) dengan terapi oksigen nasal kanul 64%. Rata rata dan standar deviasi Downe Score pra terapi oksigen adalah 3,20±2,041 dan pasca terapi adalah 1,04±1,881. Analisis data menggunakan Uji Wilcoxon menunjukkan nilai Z sebesar -4,173 dan nilai significancy sebesar 0,001 (p<0,05), dapat disimpulkan terdapat penurunan Downes score pada bayi asfiksia yang mandapat terapi oksigen.
STUDY OF CONTRACT OBJECT IN MULTI-SERVICE FINANCING USING IJARAH IN ISLAMIC BANK
Authors: Firdausi Kamalia
Published: March 2021

In a case of a dispute between an islamic bank and a customer related to multi-service financing using an ijarah contract at an islamic bank, the customer is suing for the cancellation of the contract on the multi-service financing on the grounds that the object of the contract is not the object of the contract, so the contract should be null and void. However, the court decision stated that he rejected the customer's claim. This research was conducted to examine the application of sharia principles in legal considerations in court decisions regarding contract objects in multi-service financing using the ijarah contract. This research is a normative legal research using the statutory approach method. The results of this study indicate that the legal considerations in court decisions regarding the object of the contract in multi-service financing using the ijarah contract are formally correct, but materially there is still a possibility of gharar that is not in accordance with sharia principles.
Understanding Media Ecology
Authors: Israelson Per
Published: March 2021

Dennis D. Cali, Mapping Media Ecology: Introduction to the Field (Peter Lang, 2017)

Lance Strate, Media Ecology: An Approach to Understanding the Human Condition (Peter Lang, 2017)
Prognostic Nutritional Index (PNI) in Patients With Breast Cancer Treated With Neoadjuvant Chemotherapy as a Useful Prognostic Indicator
Authors: Chen Li , Bai Ping , Kong Xiangyi , Huang Shaolong , Wang Zhongzhao , Wang Xiangyu , Fang Yi , Wang Jing
Published: March 2021

Objective

Prognostic nutritional index (PNI), calculated as serum albumin (ALB) (g/L) + 5 × total lymphocyte count (109/L), is initially used to evaluate nutritional status in patients undergoing surgery and may evaluate the therapeutic effects and predict the survival of various solid tumors. The present study aimed to evaluate the potential prognostic significance of PNI in breast cancer patients receiving neoadjuvant chemotherapy (NACT).

Methods

A total of 785 breast cancer patients treated with neoadjuvant chemotherapy were enrolled in this retrospective study. The optimal cutoff value of PNI by receiver operating characteristic curve stratified patients into a low-PNI group (<51) and a high PNI group (≥51). The associations between breast cancer and clinicopathological variables by PNI were determined by chi-square test or Fisher’s exact test. Kaplan–Meier plots and log-rank test were used to evaluate the clinical outcomes of disease-free survival (DFS) and overall survival (OS). The prognostic value of PNI was analyzed by univariate and multivariate Cox proportional hazards regression models. The toxicity of NACT was accessed by the National Cancer Institute Common Toxicity Criteria (NCI-CTC).

Results

The results indicated that PNI had prognostic significance by an optimal cutoff value of 51 on DFS and OS in univariate and multivariate Cox regression survival analyses. Breast cancer patients with a high PNI value had longer DFS and OS than those with a low PNI value [47.64 vs. 36.60 months, P < 0.0001, hazard ratio (HR) = 0.264, 95%CI = 0.160–0.435; 73.61 vs. 64.97 months, P < 0.0001, HR = 0.319, 95%CI = 0.207–0.491, respectively]. Furthermore, the results indicated that patients with high PNI had longer DFS and OS than those with low PNI in early stage and advanced breast cancer, especially in advanced breast cancer. The mean DFS and OS times for breast cancer patients with high PNI by the log-rank test were longer than in those with low PNI in different molecular subtypes. Moreover, the mean DFS and OS times in patients with high PNI by the log-rank test were longer than in those patients with low PNI without or with lymph vessel invasion. The common toxicities after neoadjuvant chemotherapy were hematologic and gastrointestinal reaction, and the PNI had no significance on the toxicities of all enrolled patients, except in anemia, leukopenia, and myelosuppression.

Conclusion

Pretreatment PNI with the advantages of being convenient, noninvasive, and reproducible was a useful prognostic indicator for breast cancer patients receiving neoadjuvant chemotherapy and is a promising biomarker for breast cancer on treatment strategy decisions.
Evaluation of Illicit Drug Consumption by Wastewater Analysis Using Polar Organic Chemical Integrative Sampler as a Monitoring Tool
Authors: Hahn Roberta Zilles , Augusto do Nascimento Carlos , Linden Rafael
Published: March 2021

Illicit drug abuse is a worldwide social and health problem, and monitoring illicit drug use is of paramount importance in the context of public policies. It is already known that relevant epidemiologic information can be obtained from the analysis of urban residual waters. This approach, named wastewater-based epidemiology (WBE), is based on the measurement of specific markers, resulting from human biotransformation of the target drugs, as indicators of the consumption of the compounds by the population served by the wastewater treatment installation under investigation. Drug consumption estimation based on WBE requires sewage sampling strategies that express the concentrations along the whole time period of time. To this end, the most common approach is the use of automatic composite samplers. However, this active sampling procedure is costly, especially for long-term studies and in limited-resources settings. An alternative, cost-effective, sampling strategy is the use of passive samplers, like the polar organic chemical integrative sampler (POCIS). POCIS sampling has already been applied to the estimation of exposure to pharmaceuticals, pesticides, and some drugs of abuse, and some studies evaluated the comparative performances of POCIS and automatic composite samplers. In this context, this manuscript aims to review the most important biomarkers of drugs of abuse consumption in wastewater, the fundamentals of POCIS sampling in WBE, the previous application of POCIS for WBE of drugs of abuse, and to discuss the advantages and disadvantages of POCIS sampling, in comparison with other strategies used in WBE. POCIS sampling is an effective strategy to obtain a representative overview of biomarker concentrations in sewage over time, with a small number of analyzed samples, increased detection limits, with lower costs than active sampling. Just a few studies applied POCIS sampling for WBE of drugs of abuse, but the available data support the use of POCIS as a valuable tool for the long-term monitoring of the consumption of certain drugs within a defined population, particularly in limited-resources settings.
A Bioinformatics Perspective on the Links Between Tetraspanin-Enriched Microdomains and Cardiovascular Pathophysiology
Authors: Sun Ge , Chen Junxiong , Ding Yingjun , Wren Jonathan D. , Xu Fuyi , Lu Lu , Wang Yan , Wang Dao-wen , Zhang Xin A.
Published: March 2021

Background:Tetraspanins and integrins are integral membrane proteins. Tetraspanins interact with integrins to modulate the dynamics of adhesion, migration, proliferation, and signaling in the form of membrane domains called tetraspanin-enriched microdomains (TEMs). TEMs also contain other cell adhesion proteins like immunoglobulin superfamily (IgSF) proteins and claudins. Cardiovascular functions of these TEM proteins have emerged and remain to be further revealed.

Objectives:The aims of this study are to explore the roles of these TEM proteins in the cardiovascular system using bioinformatics tools and databases and to highlight the TEM proteins that may functionally associate with cardiovascular physiology and pathology.

Methods:For human samples, three databases—GTEx, NCBI-dbGaP, and NCBI-GEO—were used for the analyses. The dbGaP database was used for GWAS analysis to determine the association between target genes and human phenotypes. GEO is an NCBI public repository that archives genomics data. GTEx was used for the analyses of tissue-specific mRNA expression levels and eQTL. For murine samples, GeneNetwork was used to find gene–phenotype correlations and gene–gene correlations of expression levels in mice. The analysis of cardiovascular data was the focus of this study.

Results:Some integrins and tetraspanins, such asITGA8andCd151, are highly expressed in the human cardiovascular system. TEM components are associated with multiple cardiovascular pathophysiological events in humans. GWAS and GEO analyses showed that humanCd82andITGA9are associated with blood pressure. Data from mice also suggest that various cardiovascular phenotypes are correlated with integrins and tetraspanins. For instance,Cd82andITGA9, again, have correlations with blood pressure in mice.

Conclusion:ITGA9is related to blood pressure in both species. KEGG analysis also linkedITGA9to metabolism and MAPK signaling pathway. This work provides an example of using integrated bioinformatics approaches across different species to identify the connections of structurally and/or functionally related molecules to certain categories of diseases.
Dynamic Change of Thyroid Hormones With Postmenstrual Age in Very Preterm Infants Born With Gestational Age <32 Weeks: A Multicenter Prospective Cohort Study
Authors: Shi Ranran , Zhang Ming , Chen Yao , Han Meiying , Xu Ping , Li Min , Ding Yanjie , Zhang Xiaohui , Kou Yan , Xu Haiyan , Zong Fangru , Liu Xinjian , Wang Hui , He Haiying , Liu Qiang , Kong Weikang , Niu Shiping , Li Xia , Huang Lei , Lu Qinghua , Wang Xiaofang , Deng Liping , Yang Zhenying , Zhang Xiao , Sun Rongrong , Zhao Riming , Shi Jing , Peng Fudong , Sun Xueming , Zhao Guoying , Zhao Xinfeng , Ge Yonghong , Zhang Nan , Zhu Renxia , Li Jing , Li Haiyan , Hao Huijuan , Yu Yonghui
Published: March 2021

Background

At present, the relationship between thyrotropin (TSH) and free thyroxine (FT4) in relation to postmenstrual age (PMA) in preterm infants is still unclear, and there is no reliable standard thyroid hormone reference ranges, resulting in different diagnostic criteria for congenital hypothyroidism been used by different newborn screening programs and different countries.

Objectives

To investigate the relationship between TSH/FT4 and PMA in very preterm infants (VPIs) born with gestational age (GA) <32 weeks and to derive thyroid function reference charts based on PMA.

Methods

A prospective cohort study was performed on VPIs born with GA<32 weeks and born in or transferred to the 27 neonatal intensive care units from January 1, 2019 to December 31, 2019. Serial TSH and FT4 values were measured at the end of each week during the first month after birth and also at PMA36 weeks, PMA40 weeks and at discharge, respectively. The 2.5th, 5th, 50th, 95th, and 97.5th percentiles of TSH and FT4 of different PMA groups were calculated to draw the percentile charts based on PMA.

Results

1,093 preterm infants were included in this study. The percentile charts of TSH and FT4 levels based on PMA were drawn respectively, and the result indicated that the percentile charts of TSH values were gradually increased initially and then decreased with increasing PMA. The 97.5th percentile chart reached the peak at PMA30 weeks (17.38μIU/ml), and then decreased gradually, reaching the same level as full-term infants (9.07μIU/ml) at PMA38–40 weeks. The 2.5th percentile chart of FT4 was at its lowest point at PMA26–27 weeks (5.23pmol/L), then increased slowly with PMA and reached the same level as full-term infants at PMA38–40 weeks (10.87pmol/L). At PMA36 weeks, the reference intervals of the 2.5th to 97.5th percentiles of TSH and FT4 were 1.18–12.3μIU/ml and 8.59–25.98pmol/L, respectively.

Conclusion

The percentile charts of TSH and FT4 in VPIs showed characteristic change with PMA. The results prompt that age-related cutoffs, instead of a single reference range, might be more useful to explain the thyroid function of VPIs. And repeated screening is necessary for preterm infants.
Integrated Genome-Wide Analysis of MicroRNA Expression Quantitative Trait Loci in Pig Longissimus Dorsi Muscle
Authors: Daza Kaitlyn R. , Velez-Irizarry Deborah , Casiró Sebastian , Steibel Juan P. , Raney Nancy E. , Bates Ronald O. , Ernst Catherine W.
Published: March 2021

Determining mechanisms regulating complex traits in pigs is essential to improve the production efficiency of this globally important protein source. MicroRNAs (miRNAs) are a class of non-coding RNAs known to post-transcriptionally regulate gene expression affecting numerous phenotypes, including those important to the pig industry. To facilitate a more comprehensive understanding of the regulatory mechanisms controlling growth, carcass composition, and meat quality phenotypes in pigs, we integrated miRNA and gene expression data from longissimus dorsi muscle samples with genotypic and phenotypic data from the same animals. We identified 23 miRNA expression Quantitative Trait Loci (miR-eQTL) at the genome-wide level and examined their potential effects on these important production phenotypes through miRNA target prediction, correlation, and colocalization analyses. One miR-eQTL miRNA, miR-874, has target genes that colocalize with phenotypic QTL for 12 production traits across the genome including backfat thickness, dressing percentage, muscle pH at 24 h post-mortem, and cook yield. The results of our study reveal genomic regions underlying variation in miRNA expression and identify miRNAs and genes for future validation of their regulatory effects on traits of economic importance to the global pig industry.
Evolutionary Changes in the Interaction of miRNA With mRNA of Candidate Genes for Parkinson’s Disease
Authors: Kamenova Saltanat , Aralbayeva Assel , Kondybayeva Aida , Akimniyazova Aigul , Pyrkova Anna , Ivashchenko Anatoliy
Published: March 2021

Parkinson’s disease (PD) exhibits the second-highest rate of mortality among neurodegenerative diseases. PD is difficult to diagnose and treat due to its polygenic nature. In recent years, numerous studies have established a correlation between this disease and miRNA expression; however, it remains necessary to determine the quantitative characteristics of the interactions between miRNAs and their target genes. In this study, using novel bioinformatics approaches, the quantitative characteristics of the interactions between miRNAs and the mRNAs of candidate PD genes were established. Of the 6,756 miRNAs studied, more than one hundred efficiently bound to mRNA of 61 candidate PD genes. The miRNA binding sites (BS) were located in the 5′-untranslated region (5′UTR), coding sequence (CDS) and 3′-untranslated region (3′UTR) of the mRNAs. In the mRNAs of many genes, the locations of miRNA BS with overlapping nucleotide sequences (clusters) were identified. Such clusters substantially reduced the proportion of nucleotide sequences of miRNA BS in the 5′UTRs, CDSs, and 3′UTRs. The organization of miRNA BS into clusters leads to competition among miRNAs to bind mRNAs. Differences in the binding characteristics of miRNAs to the mRNAs of genes expressed at different rates were identified. Single miRNA BS, polysites for the binding for one miRNA, and multiple BS for two or more miRNAs in one mRNA were identified. Evolutionary changes in the BS of miRNAs and their clusters in 5′UTRs, CDSs and 3′UTRs of mRNA of orthologous candidate PD genes were established. Based on the quantitative characteristics of the interactions between miRNAs and mRNAs candidate PD genes, several associations recommended as markers for the diagnosis of PD.
Disruption of Circadian Transcriptome in Lung by Acute Sleep Deprivation
Authors: Lu Yuntao , Liu Bing , Ma Junjie , Yang Shuo , Huang Ju
Published: March 2021

Inadequate sleep prevails in modern society and it impairs the circadian transcriptome. However, to what extent acute sleep deprivation (SD) has impact on the circadian rhythms of peripheral tissues is not clear. Here, we show that in mouse lung, a 10-h acute sleep deprivation can alter the circadian expression of approximately 3,000 genes. We found that circadian rhythm disappears in genes related to metabolism and signaling pathways regulating protein phosphorylation after acute sleep deprivation, while the core circadian regulators do not change much in rhythmicity. Importantly, the strong positive correlation between mean expression and amplitude (E-A correlation) of cycling genes has been validated in both control and sleep deprivation conditions, supporting the energetic cost optimization model of circadian gene expression. Thus, we reveal that acute sleep deprivation leads to a profound change in the circadian gene transcription that influences the biological functions in lung.
Dynamic Intracellular Metabolic Cell Signaling Profiles During Ag-Dependent B-Cell Differentiation
Authors: Díez Paula , Pérez-Andrés Martín , Bøgsted Martin , Azkargorta Mikel , García-Valiente Rodrigo , Dégano Rosa M. , Blanco Elena , Mateos-Gomez Sheila , Bárcena Paloma , Santa Cruz Santiago , Góngora Rafael , Elortza Félix , Landeira-Viñuela Alicia , Juanes-Velasco Pablo , Segura Victor , Manzano-Román Raúl , Almeida Julia , Dybkaer Karen , Orfao Alberto , Fuentes Manuel
Published: March 2021

Human B-cell differentiation has been extensively investigated on genomic and transcriptomic grounds; however, no studies have accomplished so far detailed analysis of antigen-dependent maturation-associated human B-cell populations from a proteomic perspective. Here, we investigate for the first time the quantitative proteomic profiles of B-cells undergoing antigen-dependent maturation using a label-free LC-MS/MS approach applied on 5 purified B-cell subpopulations (naive, centroblasts, centrocytes, memory and plasma B-cells) from human tonsils (data are available via ProteomeXchange with identifier PXD006191). Our results revealed that the actual differences among these B-cell subpopulations are a combination of expression of a few maturation stage-specific proteins within each B-cell subset and maturation-associated changes in relative protein expression levels, which are related with metabolic regulation. The considerable overlap of the proteome of the 5 studied B-cell subsets strengthens the key role of the regulation of the stoichiometry of molecules associated with metabolic regulation and programming, among other signaling cascades (such as antigen recognition and presentation and cell survival) crucial for the transition between each B-cell maturation stage.
High-Oxygen Submersion Fetal Thymus Organ Cultures Enable FOXN1-Dependent and -Independent Support of T Lymphopoiesis
Authors: Han Jianxun , Zúñiga-Pflücker Juan Carlos
Published: March 2021

T cell development is effectively supported in fetal thymus organ cultures (FTOCs), which places thymus lobes atop an air-liquid interface (ALI) culture system. The direct exposure to air is critical for its success, as fetal thymus lobes placed in low oxygen submersion (LOS)-FTOCs fail to support thymocyte development. However, submersion cultures performed in the presence of high concentration of ambient oxygen (60~80%) allow for normal thymocyte development, but the underlying mechanism for this rescue has remained elusive. Here, we show that FOXN1 expression in thymic epithelial cells (TECs) from LOS-FTOCs was greatly reduced compared to conventional ALI-FTOCs. Consequently, the expression of important FOXN1 target genes, includingDll4andCcl25, in TECs was extinguished. The loss of DLL4 and CCL25 interrupted thymocyte differentiation and led to CD4+CD8+cells exiting the lobes, respectively. High oxygen submersion (HOS)-FTOCs restored the expression of FOXN1 and its target genes, as well as maintained high levels of MHCII expression in TECs. In addition, HOS-FTOCs promoted the self-renewal of CD4−CD8−CD44−CD25+cells, allowing for the continuous generation of later stage thymocytes. Forced FOXN1 expression in TECs rescued thymocyte developmental progression, but not cellularity, in LOS-FTOCs. Given that oxidative stress has been reported to accelerate the onset of age-associated thymic involution, we postulate that regulation of FOXN1 by oxygen and antioxidants may underpin this biological process.
Integrative Transcriptome Sequencing Reveals the Molecular Difference of Maturation Process of Ovary and Testis in Mud Crab Scylla paramamosain
Authors: Cui Wenxiao , Yang Qin , Zhang Yin , Farhadi Ardavan , Fang Huan , Zheng Huaiping , Li Shengkang , Zhang Yueling , Ikhwanuddin Mhd , Ma Hongyu
Published: March 2021

The mud crab Scylla paramamosain is a species with significant sexual dimorphism in growth rate and body size, of which the females are of higher economic and nutritional values than the males. Accordingly, there is an urgent need to explore the molecular mechanism underlying sex determination and gonadal differentiation. The single-molecule long-read technology combining with RNA sequencing was employed to construct a full-length transcriptome for gonads of S. paramamosain. In total, 1,562,819 FLNC reads were obtained from 1,813,758 reads of inserts (ROIs). Among them, the 10,739 fusion isoforms corresponded to 23,634 reads and were involved in 5,369 genes in the reference annotation. According to the criteria for new transcripts, a total of 213,809 isoforms were recognized as novel transcripts and then matched against Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), NR, Swissprot, and KOG databases. We also identified 22,313 SSRs, 169,559 lncRNAs, and 25,451 SNPs. Additionally, 349,854 alternative splicing (AS) events from 8,430 gene models were detected, and 5,129 polyadenylation sites were profiled from 3,090 genes. GO and KEGG annotation indicated that AS and APA probably play important roles in the gonadal development and maturation. Besides, the DEGs associated with gonadal development and maturation were identified and analyzed based on the RNA-Seq data.
Transcriptomic, Biochemical, and Morphological Study Reveals the Mechanism of Inhibition of Pseudopestalotiopsis camelliae-sinensis by Phenazine-1-Carboxylic Acid
Authors: Yin Qiaoxiu , Yang Rui , Ren Yafeng , Yang Zhiying , Li Tao , Huang Honglin , Tang Qin , Li Dongxue , Jiang Shilong , Wu Xian , Wang Delu , Chen Zhuo
Published: March 2021

Gray blight disease is one of the most destructive diseases of tea plants and occurs widely in the tea-growing areas of the world. It is caused by several fungal phytopathogens, of whichPseudopestalotiopsis camelliae-sinensisis the main pathogen in China. The environmentally friendly antimicrobial, phenazine-1-carboxylic acid (PCA), a metabolite of the natural soil-borne bacteriaPseudomonasspp., can inhibit a range of fungal crop diseases. In this study, we determined that PCA was active againstPs. camelliae-sinensis in vitro.We studied the mode of action of PCA on hyphae using a microscopic investigation, transcriptomics, biochemical methods, and molecular docking. The results of scanning and transmission electron microscopy indicated that PCA caused developmental deformity of mycelia and organelle damage, and it significantly decreased the accumulation of exopolysaccharides on the hyphal surface. The transcriptome revealed that 1705 and 1683 differentially expressed genes ofPs. camelliae-sinensistreated with PCA were up-regulated or down-regulated, respectively, with genes associated with ribosome biogenesis, oxidative phosphorylation, and encoding various proteins ofN-glycan biosynthesis being significantly up-regulated. Up-regulation of nine genes related toN-glycan biosynthesis ofPs. camelliae-sinensisin response to PCA treatment was confirmed by reverse transcription qPCR. The enzymatic activity of catalase and superoxide dismutase of hyphae was significantly decreased by PCA treatment. Our results indicated that exposure to PCA resulted in expression changes in oxidoreductase genes, accumulation of reactive oxygen species, and decreased activity of catalase, with concomitant damage to the fungal cell membrane and cell wall.
The “Jack-of-all-Trades” Flagellum From Salmonella and E. coli Was Horizontally Acquired From an Ancestral β-Proteobacterium
Authors: Ferreira Josie L. , Coleman Izaak , Addison Max L. , Zachs Tobias , Quigley Bonnie L. , Wuichet Kristin , Beeby Morgan
Published: March 2021

The γ-proteobacteria are a group of diverse bacteria including pathogenic Escherichia, Salmonella, Vibrio, and Pseudomonas species. The majority swim in liquids with polar, sodium-driven flagella and swarm on surfaces with lateral, non-chemotactic flagella. Notable exceptions are the enteric Enterobacteriaceae such as Salmonella and E. coli. Many of the well-studied Enterobacteriaceae are gut bacteria that both swim and swarm with the same proton-driven peritrichous flagella. How different flagella evolved in closely related lineages, however, has remained unclear. Here, we describe our phylogenetic finding that Enterobacteriaceae flagella are not native polar or lateral γ-proteobacterial flagella but were horizontally acquired from an ancestral β-proteobacterium. Using electron cryo-tomography and subtomogram averaging, we confirmed that Enterobacteriaceae flagellar motors resemble contemporary β-proteobacterial motors and are distinct to the polar and lateral motors of other γ-proteobacteria. Structural comparisons support a model in which γ-proteobacterial motors have specialized, suggesting that acquisition of a β-proteobacterial flagellum may have been beneficial as a general-purpose motor suitable for adjusting to diverse conditions. This acquisition may have played a role in the development of the enteric lifestyle.
Impact of Structural Observables From Simulations to Predict the Effect of Single-Point Mutations in MHC Class II Peptide Binders
Authors: Ochoa Rodrigo , Laskowski Roman A. , Thornton Janet M. , Cossio Pilar
Published: March 2021

The prediction of peptide binders to Major Histocompatibility Complex (MHC) class II receptors is of great interest to study autoimmune diseases and for vaccine development. Most approaches predict the affinities using sequence-based models trained on experimental data and multiple alignments from known peptide substrates. However, detecting activity differences caused by single-point mutations is a challenging task. In this work, we used interactions calculated from simulations to build scoring matrices for quickly estimating binding differences by single-point mutations. We modelled a set of 837 peptides bound to an MHC class II allele, and optimized the sampling of the conformations using the Rosetta backrub method by comparing the results to molecular dynamics simulations. From the dynamic trajectories of each complex, we averaged and compared structural observables for each amino acid at each position of the 9°mer peptide core region. With this information, we generated the scoring-matrices to predict the sign of the binding differences. We then compared the performance of the best scoring-matrix to different computational methodologies that range in computational costs. Overall, the prediction of the activity differences caused by single mutated peptides was lower than 60% for all the methods. However, the developed scoring-matrix in combination with existing methods reports an increase in the performance, up to 86% with a scoring method that uses molecular dynamics.
Site-Specific Introduction of Negative Charges on the Protein Surface for Improving Global Functions of Recombinant Fetal Hemoglobin
Authors: Kettisen Karin , Dicko Cedric , Smeds Emanuel , Bülow Leif
Published: March 2021

Due to its compatible oxygen-transporting abilities, hemoglobin (Hb) is a protein of interest in the development of artificial oxygen therapeutics. Despite continuous formulation attempts, extracellular Hb solution often exhibits undesirable reactions when applied in vivo. Therefore, protein engineering is frequently used to examine alternative ways of controlling the unwanted reactions linked to cell-free Hb solutions. In this study, three mutants of human fetal hemoglobin (HbF) are evaluated; single mutants αA12D and αA19D, and a double mutant αA12D/A19D. These variants were obtained by site-directed mutagenesis and recombinant production in E. coli, and carry negative charges on the surface of the α-subunit at the designated mutation sites. Through characterization of the mutant proteins, we found that the substitutions affected the protein in several ways. As expected, the isoelectric points (pIs) were lowered, from 7.1 (wild-type) down to 6.6 (double mutant), which influenced the anion exchange chromatographic procedures by shifting conditions toward higher conductivity for protein elution. The biological and physiological properties of HbF could be improved by these small modifications on the protein surface. The DNA cleavage rate associated with native HbF could be reduced by 55%. In addition, the negatively charged HbF mutant had an extended circulation time when examined in a mouse model using top load Hb additions. At the same time, the mutations did not affect the overall structural integrity of the HbF molecule, as determined by small-angle X-ray scattering. In combination with circular dichroism and thermal stability, modest structural shifts imposed by the mutations could possibly be related to changes in secondary structure or reorganization. Such local deformations were too minor to be determined within the resolution of the structural data; and overall, unchanged oxidation and heme loss kinetics support the conclusion that the mutations did not adversely affect the basic structural properties of Hb. We confirm the value of adding negatively charged residues onto the surface of the protein to improve the global functions of recombinant Hb.
Knockdown of Long Non-coding RNA SNGH3 by CRISPR-dCas9 Inhibits the Progression of Bladder Cancer
Authors: Cao Yu , Hu Qiong , Zhang Ruiming , Li Ling , Guo Mingjuan , Wei Huiling , Zhang Li , Wang Jianfeng , Li Chunjing
Published: March 2021

Recent research evidence documents that lncRNAs (long non-coding RNAs lncRNAs) play a pivotal role in the tumorigenesis and development of tumors. LncRNA SNGH3 (small nucleolar RNA host gene 3) is highly expressed in numerous forms of cancer, serving as an oncogene in cancer progression. Nonetheless, the clinical relationship, along with the mechanism of SNGH3 in bladder cancer, have not been studied. Herein, the findings exhibited upregulation of SNGH3 in bladder cancer tissues, along with the cell lines. Furthermore, overexpressed SNGH3 was positively linked to the TNM stage, as well as the histological grade of bladder cancer. Moreover, the silencing of SNGH3, using CRISPR-dCas9, suppressed cell growth along with migration, but elevated bladder cancer cell apoptosis. In summary, we established that SNGH3 serves as a bladder cancer oncogene and could be employed as a prospective diagnostic marker for clinical use, and is also a therapeutic target for CRISPR-mediated gene therapy.
Cannabidiol Induces Autophagy to Protects Neural Cells From Mitochondrial Dysfunction by Upregulating SIRT1 to Inhibits NF-κB and NOTCH Pathways
Authors: Kang Shaolei , Li Jinglin , Yao Zhihui , Liu Jiaxin
Published: March 2021

The protective effect of Cannabidiol on Parkinson’s disease (PD) has been found in recent study. However, the specific mechanism of the protective effect of Cannabidiol on PD nerve damage require further exploration. This study aims to investigate effect of Cannabidiol on MMP-induced Neural Cells (SH-SY5Y) mitochondrial dysfunction. MMP+ and Cannabidiol were used to treat SH-SY5Y cells, the cells viability was measured by MTT assay. The expression of Tyrosine hydroxylase (TH) in cells was measured by western blotting and Immunofluorescence staining. The relationship among Cannabidiol, Silent mating type information regulation 2 homolog-1 (SIRT1) and NOTCH signaling, NF-κB signaling was examined by western blotting. The effect of Cannabidiol on MMP+-induced mitochondrial dysfunction of SH-SY5Y cells was measured by western blotting. Cannabidiol alleviated loss of TH expression and cytotoxicity in the MPP+-induced SH-SY5Y cells. Further mechanistic investigation showed that Cannabidiol induced SH-SY5Y cells autophagy to protects cells from mitochondrial dysfunction by upregulating SIRT1 to Inhibits NF-κB and NOTCH Pathways. Taken together, Cannabidiol acts as a protector in PD.