bluuebunny/crossref_metadata_2025 huggingface dataset:
Elektronik İmzalı Belgelerin Delil Değerinin Korunmasında Mevzuatta Öngörülen Delil Özelliklerinin İncelenmesi
Authors: SAĞLIK Özhan , ÇİÇEK Niyazi
Published: December 2020

E-imza teknolojileri, günümüzde e-imzalı belgelerin delil değerini koruması için sahip olması gereken özellikleri karşılayabiliyorken, ilerleyen yıllarda nasıl bir durumla karşılaşılacağıyla alakalı tereddütler henüz giderilememiştir. E-imza algoritmalarının teknolojik eskimeye uğraması, saldırı ihtimali gibi güvenlik açıkları, uygulama yazılımlarının eksikliği ve teknolojik göç yöntemleriyle ilgili sonuçların henüz yeteri kadar görülmemesi gibi çeşitli riskler söz konusudur. Bu riskler, e-imza doğrulanamazsa ya da doğrulama sırasında şüpheye düşülürse ne yapılabilir, belgelerin delil değeri nasıl korunabilir sorularını gündeme getirmektedir. E-imza ile ilgili şüpheye düşüldüğünde sertifika doğrulaması yapılmakta; bir karara varılamazsa bilirkişiye başvurulabilmektedir. Bunların yanı sıra elektronik belge yönetim sistemlerinde (EBYS) kayıt altına alınan e-imzalı belgelerin delil değerinin korunmasında başka mekanizmaların da kullanılabileceği düşünülmektedir. Bu mekanizmalardan biri olarak söz konusu belgelerin mevzuatta yer alan delil özelliklerine göre üretilip üretilmediğini değerlendirmek amacıyla kullanılabilecek bir kontrol listesinin belgelerin delil değerinin korunmasına olumlu bir katkı yapacağı kanaati savunulmaktadır. Çalışmada, nitel araştırma yöntemi kullanılmaktadır.Mevzuatta e-imzalı belgelerin sahip olması gereken özellikler,delil değerinin korunmasında bir kontrol listesi oluşturmak hedefiyle incelenmiştir.Bu kontrol listesi aracılığıyla e-imzalı belgelerin delil değerinin korunup korunmadığının değerlendirilebileceği önerilmektedir.
Olumsallık, Feminizm ve Siyaset
Authors: Ünlü Seval
Published: December 2020

Olumsallık, bir şeyin böyle olmak zorunda olmadığını ya da başka türlü olabileceğini ifade eder. Bir şeyin olumsal olması sadece zorunlu olmaması demek değil, aynı zamanda öngörülmüş amaçlarının gerçekleşmeme ya da öngörülmemiş sonuçlarının doğma olasılığı taşıdığı anlamına gelir. Bu özellikleriyle olumsallık, Hannah Arendt’in de vurguladığı, eylemin doğasına bağlı iki kısıtla maluldür: İlki eylemin geri döndürülemezliği, ikincisi ise belirsizlikler içinde meydana gelen eylemin öngörülemezliği. Feminizm, eylemin olumsallığını ehlileştirmeye yönelik erkek egemen siyaset biçimine karşı olumsallığa dayalı bir siyasal kuram ve pratik sunmaktadır. Öncelikle feminizm, temel savı itibariyle olumsaldır; kültürel olarak farklı biçimler alsa ve yüzyıllar içinde değişen farklı üretim ilişkileriyle eklemlense de ataerki, doğal ve zorunlu değildir. İkinci olarak feminizm, eylem biçimi açısından olumsaldır; gündelik hayatta ataerkiye karşı verilen her mücadele, büyük yapıların dönüştürülmesinde bir etki yaratır. Olumsallığa dayalı bir kuram ve hareket olarak feminizm, siyasete, feminist mücadelenin ötesinde daha doğrudan bir ilişkiyle bağlıdır. Feminist mücadele sadece ataerkiye karşı verilen bir mücadele değil, siyasal eylemin anlamına dair çağdaş bir deneyim kaynağıdır. Feminist kuram, sadece toplumlara kök salmış erkek egemenliğini değil, ortak yaşamın ortaklaşa düzenlenmesi anlamında genel olarak siyaseti de kuramlaştıracak araçlar sunar. Dolayısıyla feminizm bir yandan siyaset kuramından beslenirken, diğer yandan oluşturduğu deneyim mirasıyla siyaset kuramının ufkunun belirlenmesinde rol oynayan bir kaynaktır. Bu çalışmada, Arendt’in işaret ettiği tarzda olumsallığa dayalı bir siyasal eylemin pusulası olabilecek ilkeleri feminizmden doğru düşünmenin olanakları ve bunun geniş anlamda siyasal eyleme katkıları ele alınacaktır.
‘Şule Çet İçin Adalet’: Twitter Verisinin Eleştirel Söylem Çözümlemesi Modeli ile İncelenmesi
Authors: Okray Zihniye
Published: December 2020

Kadın cinayetleri sadece Türkiye’de değil dünya çapında çözülmeyi bekleyen önemli bir sorundur. Kadın cinayetleri femicide kavramının Türkçe alanyazın içerisinde kullanılan en yaygın tanımıdır. Kadın cinayeti denildiğinde en basit anlamda kadının sadece kadın olduğu için öldürülmesinin ifadesidir. Bu çalışmada Şule Çet cinayeti ardından mikro-blog olan sosyal paylaşım sitesi Twitter verilerinin geriye dönük olarak taranması ve eleştirel söylem çözümlemesi ile araştırılmasını kapsamaktadır. Şule çet için adalet hastag’i ile oluşturulan mikro-bloğun incelenmesi ve analizleri sonucunda elde edilen bulgular arasında Türkiye’deki adelet sisteminin eril bir adalet olduğu, kadınların cinsel hayatlarının, bekar ve çalışıyor olmalarının, ailelerinde uzak yaşıyor olmalarının, giyim tarzlarının tecavüzü ve cinayeti meşrulaştıran kavramlar olarak görüldüğü sonuçlarına ulaşılmıştır. Yapılan incelemeler sonucunda geçtiğimiz yıllarda yine Türkiye’de işlenen tecavüz ve cinayetlere göndermeler yapılmış ve adaletin sağlanması için çağrılar yapılmıştır. Ayrıca ayrıcalıklı gruplara uygulanan cinsel tacizler de kınanmıştır.
The Effect of Socio-Cultural Norms on Female Labor Force Participation in Afghanistan
Authors: Parlaktuna İnci , Sediqi Sediqa
Published: December 2020

This study based on the review of literature in Afghanistan, collected quantitative data through sequentially structured questionnaires to determine cultural effects on FLFP in Afghanistan. In this purpose, the study aims to use two types of data collection to determine the main research question on “whether socio-cultural norms affect the employability of women”. The results provide evidence based on the purpose of the study that, socio-cultural norms affect women’s employability regardless of their educational level, employment status and the region’s level of development. Though most of the respondents of the survey were educated,  majority of single educated women were the ones who were busy working in service, the industry as well as the agriculture sector. While this case is not true, for married educated women due to social norms and conservatism as one of the major reasons behind their unemployment to enter the job market.
Boosting adults scientific literacy with experiential learning practices
Authors: Dopico Eduardo , Ardura Alba , Borrell Yaisel J. , Miralles Laura , García-Vázquez Eva
Published: December 2020

Working as an interdisciplinary team, from the departments of Education and Biology we organized a short experiential learning seminar followed by a hands-on workshop for the promotion of citizen scientific literacy. Participants were adult lifelong learners enrolled in University programs, and others were adults interested in scientific activities without a motivation towards continuous learning. Through a teaching dynamic based on learning science by doing science, they could make close contact with the research procedures in scientific laboratories and learn about the use of DNA to identify unknown fish species. The data collected about their learning gains in this science literacy experience showed that elder lifelong learners found the basic scientific concepts more difficult to understand than the non-lifelong learners, but were more motivated to engage in science education activities than the latter, which makes them a very interesting potential group to recruit for citizen science initiatives.
Stem Cell-Friendly Scaffold Biomaterials: Applications for Bone Tissue Engineering and Regenerative Medicine
Authors: Zhang Yongtao , Wu Di , Zhao Xia , Pakvasa Mikhail , Tucker Andrew Blake , Luo Huaxiu , Qin Kevin H. , Hu Daniel A. , Wang Eric J. , Li Alexander J. , Zhang Meng , Mao Yukun , Sabharwal Maya , He Fang , Niu Changchun , Wang Hao , Huang Linjuan , Shi Deyao , Liu Qing , Ni Na , Fu Kai , Chen Connie , Wagstaff William , Reid Russell R. , Athiviraham Aravind , Ho Sherwin , Lee Michael J. , Hynes Kelly , Strelzow Jason , He Tong-Chuan , El Dafrawy Mostafa
Published: December 2020

Bone is a dynamic organ with high regenerative potential and provides essential biological functions in the body, such as providing body mobility and protection of internal organs, regulating hematopoietic cell homeostasis, and serving as important mineral reservoir. Bone defects, which can be caused by trauma, cancer and bone disorders, pose formidable public health burdens. Even though autologous bone grafts, allografts, or xenografts have been used clinically, repairing large bone defects remains as a significant clinical challenge. Bone tissue engineering (BTE) emerged as a promising solution to overcome the limitations of autografts and allografts. Ideal bone tissue engineering is to induce bone regeneration through the synergistic integration of biomaterial scaffolds, bone progenitor cells, and bone-forming factors. Successful stem cell-based BTE requires a combination of abundant mesenchymal progenitors with osteogenic potential, suitable biofactors to drive osteogenic differentiation, and cell-friendly scaffold biomaterials. Thus, the crux of BTE lies within the use of cell-friendly biomaterials as scaffolds to overcome extensive bone defects. In this review, we focus on the biocompatibility and cell-friendly features of commonly used scaffold materials, including inorganic compound-based ceramics, natural polymers, synthetic polymers, decellularized extracellular matrix, and in many cases, composite scaffolds using the above existing biomaterials. It is conceivable that combinations of bioactive materials, progenitor cells, growth factors, functionalization techniques, and biomimetic scaffold designs, along with 3D bioprinting technology, will unleash a new era of complex BTE scaffolds tailored to patient-specific applications.
miR-140-5p in Small Extracellular Vesicles From Human Papilla Cells Stimulates Hair Growth by Promoting Proliferation of Outer Root Sheath and Hair Matrix Cells
Authors: Chen Yuxin , Huang Junfei , Liu Zhen , Chen Ruosi , Fu Danlan , Yang Lunan , Wang Jin , Du Lijuan , Wen Lihong , Miao Yong , Hu Zhiqi
Published: December 2020

The application of dermal papilla cells to hair follicle (HF) regeneration has attracted a great deal of attention. However, cultured dermal papilla cells (DPCs) tend to lose their capacity to induce hair growth during passage, restricting their usefulness. Accumulating evidence indicates that DPCs regulate HF growth mainly through their unique paracrine properties, raising the possibility of therapies based on extracellular vesicles (EVs). In this study, we explored the effects of EVs from high- and low-passage human scalp follicle dermal papilla cells (DP-EVs) on activation of hair growth, and investigated the underlying mechanism. DP-EVs were isolated by ultracentrifugation and cultured with human scalp follicles, hair matrix cells (MxCs), and outer root sheath cells (ORSCs), and we found low-passage DP-EVs accelerated HF elongation and cell proliferation activation. High-throughput miRNA sequencing and bioinformatics analysis identified 100 miRNAs that were differentially expressed between low- (P3) and high- (P8) passage DP-EVs. GO and KEGG pathway analysis of 1803 overlapping target genes revealed significant enrichment in the BMP/TGF-β signaling pathways. BMP2 was identified as a hub of the overlapping genes. miR-140-5p, which was highly enriched in low-passage DP-EVs, was identified as a potential regulator of BMP2. Direct repression of BMP2 by miR-140-5p was confirmed by dual-luciferase reporter assay. Moreover, overexpression and inhibition of miR-140-5p in DP-EVs suppressed and increased expression of BMP signaling components, respectively, indicating that this miRNA plays a critical role in hair growth and cell proliferation. DP-EVs transport miR-140-5p from DPCs to epithelial cells, where it downregulates BMP2. Therefore, DPC-derived vesicular miR-140-5p represents a therapeutic target for alopecia.
Non-genetic Heterogeneity of Macrophages in Diseases—A Medical Perspective
Authors: Gessain Grégoire , Blériot Camille , Ginhoux Florent
Published: December 2020

Macrophages are sessile immune cells with a high functional plasticity. Initially considered as a uniform population of phagocytic scavengers, it is now widely accepted that these cells also assume developmental and metabolic functions specific of their tissue of residence. Hence, the paradigm is shifting while our comprehension of macrophage heterogeneity improves. Accordingly, exploiting this intrinsic versatility appears more and more promising for the establishment of innovative therapeutic strategies. Nevertheless, identifying relevant therapeutic targets remains a considerable challenge. Herein, we discuss various features of macrophage heterogeneity in five main categories of human diseases: infectious, inflammatory, metabolic, age-related, and neoplastic disorders. We summarize the current understanding of how macrophage heterogeneity may impact the pathogenesis of these diseases and propose a comprehensive overview with the aim to help in establishing future macrophage-targeted therapies.
Effects of the Molecular Weight of Hyaluronic Acid in a Carbon Nanotube Drug Delivery Conjugate
Authors: Arpicco Silvia , Bartkowski Michał , Barge Alessandro , Zonari Daniele , Serpe Loredana , Milla Paola , Dosio Franco , Stella Barbara , Giordani Silvia
Published: December 2020

Hyaluronic acid (HA) is a ubiquitous biopolymer involved in many pathophysiological roles. One HA receptor, the cluster of differentiation CD44 protein, is often overexpressed in tumor cells. As such, HA has attracted considerable interest in the development of drug delivery formulations, given its intrinsic targetability toward CD44 overexpressing cells. The present study is focused on examining the correlation of HA molecular weight with its targetability properties. A library of conjugates obtained by linking the amino group of the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) to the carboxylic residues of HA of different molecular weight (6.4, 17, 51, 200, and 1,500 kDa) were synthesized and fully characterized. The HA-DMPE conjugates were then used to non-covalently functionalize the highly hydrophobic single-walled carbon nanotubes (CNT), and further encapsulate the anticancer drug doxorubicin (DOX). Our results show that the complexes DOX/CNT/HA-DMPE maintain very good and stable dispersibility. Drug release studies indicated a pH-responsive release of the drug from the nanocarrier. Cell viability tests demonstrated that all HA modified CNTs have good biocompatibility, and specific targeting toward cells overexpressing the CD44 receptor. Among all the molecular weights tested, the 200 kDa HA showed the highest increase in cellular uptake and cytotoxic activity. All these promising attributes make CNT/HA200-DMPE a “smart” platform for tumor-targeted delivery of anticancer agents.
The Role of the Interleukin-17 Axis and Neutrophils in the Pathogenesis of Endemic and Systemic Mycoses
Authors: Puerta-Arias Juan David , Mejía Susana P. , González Ángel
Published: December 2020

Systemic and endemic mycoses are considered life-threatening respiratory diseases which are caused by a group of dimorphic fungal pathogens belonging to the generaHistoplasma,Coccidioides,Blastomyces,Paracoccidioides,Talaromyces, and the newly described pathogenEmergomyces. T-cell mediated immunity, mainly T helper (Th)1 and Th17 responses, are essential for protection against these dimorphic fungi; thus, IL-17 production is associated with neutrophil and macrophage recruitment at the site of infection accompanied by chemokines and proinflammatory cytokines production, a mechanism that is mediated by some pattern recognition receptors (PRRs), including Dectin-1, Dectine-2, TLRs, Mannose receptor (MR), Galectin-3 and NLPR3, and the adaptor molecules caspase adaptor recruitment domain family member 9 (Card9), and myeloid differentiation factor 88 (MyD88). However, these PRRs play distinctly different roles for each pathogen. Furthermore, neutrophils have been confirmed as a source of IL-17, and different neutrophil subsets and neutrophil extracellular traps (NETs) have also been described as participating in the inflammatory process in these fungal infections. However, both the Th17/IL-17 axis and neutrophils appear to play different roles, being beneficial mediating fungal controls or detrimental promoting disease pathologies depending on the fungal agent. This review will focus on highlighting the role of the IL-17 axis and neutrophils in the main endemic and systemic mycoses: histoplasmosis, coccidioidomycosis, blastomycosis, and paracoccidioidomycosis.
Climate Extreme Seeds a New Domoic Acid Hotspot on the US West Coast
Authors: Trainer Vera L. , Kudela Raphael M. , Hunter Matthew V. , Adams Nicolaus G. , McCabe Ryan M.
Published: December 2020

A heatwave that blanketed the northeast Pacific Ocean in 2013–2015 had severe impacts on the marine ecosystem through altered species composition and survival. A direct result of this marine heatwave was a sustained, record-setting harmful algal bloom (HAB), caused by the toxigenic diatom, Pseudo-nitzschia, that led to an unprecedented delay in harvest opportunity for commercial Dungeness crab (Metacarcinus magister) and closure of other recreational, commercial and tribal shellfish harvest, including razor clams. Samples collected during a cruise in summer 2015, showed the appearance of a highly toxic “hotspot” between Cape Mendocino, CA and Cape Blanco, OR that was observed again during cruises in the summers of 2016–2018. The transport of toxic cells from this retentive site northward during wind relaxations or reversals associated with storms resulted in economically debilitating delay or closure of Dungeness crab harvest in both northern California and Oregon in 2015–2019. Analyses of historic large-scale Pseudo-nitzschia HABs have shown that these events occur during warm periods such as El Niño, positive phases of the Pacific Decadal Oscillation, or the record-setting marine heatwave. In order to reduce the impacts of large-scale HABs along the west coast of North America, early warning systems have been developed to forewarn coastal managers. These early warning systems include the Pacific Northwest and California HAB Bulletins, both of which have documented elevated domoic acid and increased risk associated with the northern California hotspot. These early warnings enable mitigative actions such as selective opening of safe harvest zones, increased harvest limits during low risk periods, and early harvest in anticipation of impending HAB events. The aims of this study are to show trends in nearshore domoic acid along the US west coast in recent years, including the recent establishment of a new seed bed of highly-toxic Pseudo-nitzschia, and to explore how early warning systems are a useful tool to mitigate the human and environmental health and economic impacts associated with harmful algal blooms.
Sex-Related Differences in Catheter Ablation for Patients With Atrial Fibrillation and Heart Failure
Authors: Chibber Tamanna , Baranchuk Adrian
Published: December 2020

The coexistence of atrial fibrillation and heart failure significantly increases the risk of all-cause mortality and heart failure hospitalizations. Sex-related differences in all patients undergoing atrial fibrillation catheter ablation include the referral of fewer women for catheter ablation (15–25%), older age of women at ablation, and higher risk of post-ablation recurrence of atrial fibrillation. We searched the existing literature for sex-related differences in patients undergoing atrial fibrillation catheter ablation with a focus on heart failure. Randomized controlled trials assessing atrial fibrillation catheter ablation in patients with heart failure have demonstrated a significant reduction in all-cause mortality and heart failure hospitalizations. Within the eight existing randomized controlled trials on heart failure with reduced ejection fraction, women composed a small proportion of the study population. Only two studies (CASTLE-AF and AATAC-HF) specifically assessed the effect of gender on outcome and showed no difference in post-ablation outcomes. Registry data-based studies assessing sex-related differences in atrial fibrillation catheter ablation in heart failure reveal that women are half as likely as men to undergo ablation. Conflicting data exist on the interaction of gender and heart failure as they may affect peri-ablation and post-ablation long-term outcomes such as atrial fibrillation recurrence or heart failure hospitalizations. In conclusion, existing studies provide insight into the gender-based differences in patients undergoing catheter ablation for atrial fibrillation as it pertains to heart failure. Further prospective studies with higher proportions of female participants are required to accurately determine gender-based differences in this population.
Increased Insulin Concentrations During Growth Hormone Treatment in Girls With Turner Syndrome Are Ameliorated by Hormone Replacement Therapy
Authors: Segerer Sabine Elisabeth , Segerer Stephan Georg , Partsch Carl-Joachim , Becker Wolfgang , Nawroth Frank
Published: December 2020

Objective

Turner syndrome (TS) is characterized by complete or partial loss of one sex chromosome and is commonly associated with short stature, metabolic changes (such as central obesity, abnormal glucose tolerance and high triglycerides) and premature ovarian insufficiency (POI). Primary management of TS during childhood and adolescence comprises treatment with human growth hormone (hGH) and, in cases with early loss of ovarian function, hormone replacement therapy (HRT). Given that metabolic parameters are altered when HRT is applied during menopause, we analyzed whether metabolic changes might be positively or negatively affected within 10 years after HRT and/or hGH in girls with TS.

Design

Observational study.

Methods

Data were collected from the medical records of 31 girls with TS attending two endocrinologic centers in Germany between 2000 and 2020. Descriptive statistics are reported as the mean ± SEM or percentages.

Results

The mean age at first presentation was 99.06 ± 8.07 months, the mean height was 115.8 ± 3.94 cm, and the mean BMI 19.0 ± 0.99 was kg/m2. Treatment with hGH was given to 96.8% of the girls, starting at an average age of 99.06 ± 8.70 months, and was continued for 67.53 ± 6.28 months. HRT was administered to 80.6% of all patients and was started at a mean age of 164.4 ± 4.54 months. During the follow-up, we did not observe any significant absolute changes in lipid parameters, but we detected beneficial effects of childhood hGH: significantly lower cholesterol (-0.206/month; p = 0.006), lower low density lipoprotein cholesterol (-0.216/month; p = 0.004), and higher high density lipoprotein cholesterol (+0.095/month; p = 0.048). Insulin concentrations, showed a significant increase attributable to hGH treatment (+0.206/month; p = 0.003), which was ameliorated by concomitant or subsequent HRT (-0.143/month; p = 0.039).

Conclusion

Treatment with hGH and HRT is provided to most girls with TS. Metabolic effects are associated with both modalities. Monitoring of metabolic changes appears to be important to detect unfavorable effects, and could guide treatment adjustment and duration.
Foraging in Urban Environments Increases Bactericidal Capacity in Plasma and Decreases Corticosterone Concentrations in White Ibises
Authors: Cummings Caroline R. , Khan Nicola Y. , Murray Maureen M. , Ellison Taylor , Welch Catharine N. , Hernandez Sonia M. , Navara Kristen J.
Published: December 2020

As humans continue to infringe on natural habitats, more animals are exposed to urbanization and its associated challenges. It is still unclear, however, whether the movement of animals into urban habitats negatively influences the health and/or survival of those animals, however those animals often experience shifts in resource availability, diet composition, and exposure to stimuli that are new and potentially stressful. Recently, white ibises (Eudocimus albus) have become increasingly common in urban habitats where they forage in close proximity to humans and even interact with them, collecting food handouts. We hypothesized that foraging in urban habitats would negatively impact measures of health, impair innate immunity, trigger elevated concentrations of corticosterone, and depress physiological responses to stressors in white ibises. We found that plasma from birds captured from urban sites had higher bactericidal capacity against Escherichia coli than those captured in natural sites. Additionally, adults captured in urban habitats had a significantly lower baseline corticosterone concentrations during the post-breeding season, and corticosterone responses to a handling challenge were lower for birds captured from urban sites during year 2 of the study. These results indicate that exposure to urban habitats impacts ibis health, though in the opposite direction of what was predicted.
Aberrantly Methylated-Differentially Expressed Genes Identify Novel Atherosclerosis Risk Subtypes
Authors: Xue Yuzhou , Guo Yongzheng , Luo Suxin , Zhou Wei , Xiang Jing , Zhu Yuansong , Xiang Zhenxian , Shen Jian
Published: December 2020

Increasing evidence has indicated that modulation of epigenetic mechanisms, especially methylation and long-non-coding RNA (lncRNA) regulation, plays a pivotal role in the process of atherosclerosis; however, few studies focused on revealing the epigenetic-related subgroups during atherosclerotic progression using unsupervised clustering analysis. Hence, we aimed to identify the epigenetics-related differentially expressed genes associated with atherosclerosis subtypes and characterize their clinical utility in atherosclerosis. Eighty samples with expression data (GSE40231) and 49 samples with methylation data (GSE46394) from a large artery plaque were downloaded from the GEO database, and aberrantly methylated–differentially expressed (AMDE) genes were identified based on the relationship between methylation and expression. Furthermore, we conducted weighted correlation network analysis (WGCNA) and co-expression analysis to identify the core AMDE genes strongly involved in atherosclerosis. K-means clustering was used to characterize two subtypes of atherosclerosis in GSE40231, and then 29 samples were recognized as validation dataset (GSE28829). In a blood sample cohort (GSE90074), chi-square test and logistic analysis were performed to explore the clinical implication of the K-means clusters. Furthermore, significance analysis of microarrays and prediction analysis of microarrays (PAM) were applied to identify the signature AMDE genes. Moreover, the classification performance of signature AMDE gene-based classifier from PAM was validated in another blood sample cohort (GSE34822). A total of 1,569 AMDE mRNAs and eight AMDE long non-coding RNAs (lncRNAs) were identified by differential analysis. Through the WGCNA and co-expression analysis, 32 AMDE mRNAs and seven AMDE lncRNAs were identified as the core genes involved in atherosclerosis development. Functional analysis revealed that AMDE genes were strongly related to inflammation and axon guidance. In the clinical analysis, the atherosclerotic subtypes were associated with the severity of coronary artery disease and risk of adverse events. Eight genes, including PARP15, SERGEF, PDGFD, MRPL45, UBR1, STAU1, WIZ, and LSM4, were selected as the signature AMDE genes that most significantly differentiated between atherosclerotic subtypes. Ultimately, the area under the curve of signature AMDE gene-based classifier for atherosclerotic subtypes was 0.858 and 0.812 in GSE90074 and GSE34822, respectively. This study identified the AMDE genes (lncRNAs and mRNAs) that could be implemented in clinical clustering to recognize high-risk atherosclerotic patients.
Targeting Low-Phytate Soybean Genotypes Without Compromising Desirable Phosphorus-Acquisition Traits
Authors: Kuerban Mireadili , Jiao Wenfeng , Pang Jiayin , Jing Jingying , Qiu Li-Juan , Ding Wenli , Cong Wen-Feng , Zhang Fusuo , Lambers Hans
Published: December 2020

Phytate-phosphorus (P) in food and feed is not efficiently utilized by humans and non-ruminant livestock, potentially contributing to high losses of P to the environment. Crops with high P-acquisition efficiency can access soil P effectively. It remains elusive whether crop genotypes with high P-acquisition efficiency can also have low seed phytate concentrations. A core collection of 256 soybean [Glycine max (L.) Merr.] genotypes from China with diverse genetic background were grown in the same environment and seeds were sampled to screen for seed phytate-P concentration. Some of these genotypes were also grown in a low-P soil in the glasshouse to measure root morphological and physiological traits related to P acquisition. Large genotypic variation was found in seed phytate-P concentration (0.69–5.49 mg P g–1 dry weight), total root length, root surface area, rhizosheath carboxylates, and acid phosphatase activity in rhizosheath soil. Geographically, seed phytate-P concentration was the highest for the genotypes from Hainan Province, whereas it was the lowest for the genotypes from Inner Mongolia. Seed phytate-P concentration showed no correlation with any desirable root traits associated with enhanced P acquisition. Two genotypes (Siliyuan and Diliuhuangdou-2) with both low phytate concentrations and highly desirable P-acquisition traits were identified. This is the first study to show that some soybean genotypes have extremely low seed phytate concentrations, combined with important root traits for efficient P acquisition, offering material for breeding genotypes with low seed phytate-P concentrations.
Early-Life Stress Alters Synaptic Plasticity and mTOR Signaling: Correlation With Anxiety-Like and Cognition-Related Behavior
Authors: Wang Anfeng , Zou Xiaojuan , Wu Jiajia , Ma Qingyu , Yuan Naijun , Ding Fengmin , Li Xiaojuan , Chen Jiaxu
Published: December 2020

Early-life stress (ELS) predisposes individuals to psychiatric disorders, including anxiety and depression, and cognitive impairments later in life. However, the underlying molecular mechanisms are not completely understood. Developmental deficits in hippocampal synaptic plasticity are among the primary detrimental alterations in brain function induced by ELS. Impaired synaptic plasticity is usually accompanied by decreased synaptic proteins, such as postsynaptic density 95 (PSD95) and synaptophysin, which are important for synaptic function. The mTOR signaling pathway plays a vital role in regulating protein translation, and mTOR activation is functionally associated with synaptic protein synthesis. In the present study, we observed whether ELS impacts synaptic protein synthesis and mTOR signaling, which is involved in synaptic plasticity. Herein, we established a maternal separation (MS) and chronic restraint stress (CRS) model and evaluated anxiety-like behavior and cognitive function (e.g., learning and memory) in adulthood through behavioral examination and analyzed hippocampal expression levels of PSD95 and synaptophysin. To explore whether the mTOR signaling pathway was associated with ELS, we also examined the activity of mTOR and s6. The behavior tests indicated that maternally separated mice showed increased anxiety-like behavior and cognitive impairments. PSD95 and synaptophysin mRNA and protein expression levels were decreased in the hippocampus, and phosphorylated mTOR and phosphorylated s6 were significantly decreased in maternally separated mice vs. those not exposed to MS. Our data demonstrate that MS impairs synaptic plasticity and inhibits mTOR signaling, specifically via s6. Therefore, we speculate that ELS decreased synaptic plasticity via the inhibition of the mTOR pathway in the hippocampus, which may underlie vulnerability to stress and mental disorders in adulthood.
Classification and Computational Analysis of Arabidopsis thaliana Sperm Cell-Specific F-Box Protein Gene 3p.AtFBP113
Authors: Malik Afsheen , Gul Alvina , Amir Rabia , Munir Faiza , Babar Mustafeez Mujtaba , Bakhtiar Syeda Marriam , Hayat Muhammad Qasim , Paracha Rehan Zafar , Khalid Zoya , Alipour Hadi
Published: December 2020

In plants, F-box proteins (FBPs) constitute one of the largest superfamilies of regulatory proteins. Most F-box proteins are shown to be an integral part of SCF complexes, which carry out the degradation of proteins and regulate diverse important biological processes. Anthers and pollen development have a huge importance in crop breeding. Despite the vast diversity of FBPs in Arabidopsis male reproductive organs, their role in anther and pollen development is not much explored. Moreover, a standard nomenclature for naming FBPs is also lacking. Here, we propose a standard nomenclature for naming the FBPs of Arabidopsis thaliana uniformly and carry out a systematic analysis of sperm cell-specific FBP gene, i.e., 3p.AtFBP113 due to its reported high and preferential expression, for detailed functional annotation. The results revealed that 3p.AtFBP113 is located on the small arm of chromosome and encodes 397 amino acid long soluble, stable, and hydrophilic protein with the possibility of localization in various cellular compartments. The presence of the C-terminal F-box associated domain (FBA) with immunoglobulin-like fold anticipated its role in protein binding. Gene ontology based functional annotation and tissue-specific gene co-expression analysis further strengthened its role in protein binding and ubiquitination. Moreover, various potential post/co-translational modifications were anticipated and the predicted tertiary structure also showed the presence of characteristic domains and fold. Thus, the outcomes of the study will be useful in developing a better understating of the function of 3p.AtFBP113 during the process of pollen development, which will be helpful for targeting the gene for manipulation of male fertility that has immense importance in hybrid breeding.
Characterization of Genome-Wide DNA Methylation and Hydroxymethylation in Mouse Arcuate Nucleus of Hypothalamus During Puberty Process
Authors: Shen Yihang , Zhou Shasha , Zhao Xiaodong , Li Hua , Sun Jielin
Published: December 2020

Background: Pulsatile pituitary gonadotropin secretion governed by hypothalamic gonadotropin-releasing hormone (GnRH) is essential for the pubertal onset. The epigenetic mechanism underlying the activation of GnRH-dependent regulatory axis in hypothalamus remains elusive. This study aims to explore the potential correlation between the signature of DNA (hydroxyl)methylation and pubertal process.

Methods: Hypothalamic arcuate nucleus (ARC) of mouse at early (4-weeks) and late pubertal (8-weeks) stages underwent RNA-, RRBS-, and RRHP-seq to investigate the genome-wide profiles of transcriptome, differential DNA methylation and hydroxymethylation.

Results: A series of differential expressed genes (DEGs) involved in sexual development could be separated into three subgroups with the significant difference of DNA methylation or hydroxymethylation or both in promoter regions. Compared to DNA methylation, DNA hydroxymethylation partook in more signaling pathways including synapse morphology, channel activity and glial development, which could enhance transsynaptic change and glia-to-neuron communication to faciliate GnRH release. The correlation between transcription and these epigenetic modifications indicated that DNA hydroxymethylation impacted with gene transcription independently of DNA methylation spanning puberty.

Conclusion: Our results characterized the hydroxymethylation pattern and provided an insight into the novel epigenetic regulation on gene expression during pubertal process.
Systems Immunology Analysis Reveals an Immunomodulatory Effect of Snail-p53 Binding on Neutrophil- and T Cell-Mediated Immunity in KRAS Mutant Non-Small Cell Lung Cancer
Authors: Hammoudeh Sarah Musa , Venkatachalam Thenmozhi , Ansari Abdul Wahid , Bendardaf Riyad , Hamid Qutayba , Rahmani Mohamed , Hamoudi Rifat
Published: December 2020

Immunomodulation and chronic inflammation are important mechanisms utilized by cancer cells to evade the immune defense and promote tumor progression. Therefore, various efforts were focused on the development of approaches to reprogram the immune response to increase the immune detection of cancer cells and enhance patient response to various types of therapy. A number of regulatory proteins were investigated and proposed as potential targets for immunomodulatory therapeutic approaches including p53 and Snail. In this study, we investigated the immunomodulatory effect of disrupting Snail-p53 binding induced by the oncogenic KRAS to suppress p53 signaling. We analyzed the transcriptomic profile mediated by Snail-p53 binding inhibitor GN25 in non-small cell lung cancer cells (A549) using Next generation whole RNA-sequencing. Notably, we observed a significant enrichment in transcripts involved in immune response pathways especially those contributing to neutrophil (IL8) and T-cell mediated immunity (BCL6, and CD81). Moreover, transcripts associated with NF-κB signaling were also enriched which may play an important role in the immunomodulatory effect of Snail-p53 binding. Further analysis revealed that the immune expression signature of GN25 overlaps with the signature of other therapeutic compounds known to exhibit immunomodulatory effects validating the immunomodulatory potential of targeting Snail-p53 binding. The effects of GN25 on the immune response pathways suggest that targeting Snail-p53 binding might be a potentially effective therapeutic strategy.
MCAM/CD146 Signaling via PLCγ1 Leads to Activation of β1-Integrins in Memory T-Cells Resulting in Increased Brain Infiltration
Authors: Zondler Lisa , Herich Sebastian , Kotte Petra , Körner Katharina , Schneider-Hohendorf Tilman , Wiendl Heinz , Schwab Nicholas , Zarbock Alexander
Published: December 2020

Multiple sclerosis is a chronic auto-inflammatory disease of the central nervous system affecting patients worldwide. Neuroinflammation in multiple sclerosis is mainly driven by peripheral immune cells which invade the central nervous system and cause neurodegenerative inflammation. To enter the target tissue, immune cells have to overcome the endothelium and transmigrate into the tissue. Numerous molecules mediate this process and, as they determine the tissue invasiveness of immune cells, display great therapeutic potential. Melanoma cell adhesion molecule (MCAM) is a membrane-anchored glycoprotein expressed by a subset of T-cells and MCAM+ T-cells have been shown to contribute to neuroinflammation in multiple sclerosis. The role of the MCAM molecule for brain invasion, however, remained largely unknown. In order to investigate the role of the MCAM molecule on T-cells, we used different in vitro and in vivo assays, including ex vivo flow chambers, biochemistry and microscopy experiments of the mouse brain. We demonstrate that MCAM directly mediates adhesion and that the engagement of MCAM induces intracellular signaling leading to β1-integrin activation on human T-cells. Furthermore, we show that MCAM engagement triggers the phosphorylation of PLCγ1 which is required for integrin activation and thus amplification of the cellular adhesive potential. To confirm the physiological relevance of our findings in vivo, we demonstrate that MCAM plays an important role in T-cell recruitment into the mouse brain. In conclusion, our data demonstrate that MCAM expressed on T-cells acts as an adhesion molecule and a signaling receptor that may trigger β1-integrin activation via PLCγ1 upon engagement.
Surface Microornamentation of Demosponge Sterraster Spicules, Phylogenetic and Paleontological Implications
Authors: Cárdenas Paco
Published: December 2020

Siliceous spicules in demosponges exist in a variety of shapes, some of which look like minute spheres of glass. They are called “sterrasters” when they belong to the Geodiidae family (Tetractinellida order) and “selenasters” when they belong to the Placospongiidae family (Clionaida order). Today, the Geodiidae represent a highly diverse sponge family with more than 340 species, occurring in shallow to deep waters worldwide, except for the Antarctic. The molecular phylogeny of Geodiidae is currently difficult to interpret because we are lacking morphological characters to support most of its clades. To fill this knowledge gap, the surface microornamentations of sterrasters were compared in different genera. Observations with scanning electron microscopy revealed four types of surfaces, which remarkably matched some of the Geodiidae genera: type I characteristic of Geodia, type II characteristic of Pachymatisma, Caminus, and some Erylus; type III characteristic of other Erylus; type IV characteristic of Caminella. Two subtypes were identified in Geodia species: warty vs. smooth rosettes. These different microornamentations were mapped on new Geodiidae COI (Folmer fragment) and 28S (C1–D2) phylogenetic trees. The monophyly of the Geodiidae was once again challenged, thereby suggesting that sterrasters have evolved independently at least three times: in the Geodiinae, in the Erylinae and in Caminella. Surface microornamentations were used to review the fossil record of sterrasters and selenasters through the paleontology literature and examination of fossils. It was concluded that “rhaxes” in the literature may represent mixes of sterrasters and selenasters: while Rhaxella spicules may belong to the Placospongiidae, Rhaxelloides spicules belong to the Geodiidae. The putative Geodiidae fossil genera, Geoditesia, and Geodiopsis, are reallocated to Tetractinellida incertae sedis. Isolated Miocene-Pliocene fossil sterrasters Hataina (Huang, 1967), Silicosphaera (Hughes, 1985) and Conciliaspongia (Robinson and Haslett, 1995) become junior synonyms of Geodia (Lamarck, 1815). Overall, the fossil record suggested that Geodiidae was present at least since the Middle Jurassic (163–166 Mya), while Geodia sterrasters were present since the Santonian/Campanian boundary, Late Cretaceous (83.6 Mya).

ZooBank Article Registration

urn:lsid:zoobank.org:pub:91B1B3AC-8862-4751-B272-8A3BDF4DEE77.
Mate Choice Contributes to the Maintenance of Shell Color Polymorphism in a Marine Snail via Frequency-Dependent Sexual Selection
Authors: Estévez Daniel , Kozminsky Eugene , Carvajal-Rodríguez Antonio , Caballero Armando , Faria Rui , Galindo Juan , Rolán-Alvarez Emilio
Published: December 2020

Natural color polymorphisms are widespread across animal species and usually have a simple genetic basis. This makes them an ideal system to study the evolutionary mechanisms responsible for maintaining biodiversity. In some populations of the intertidal snail Littorina fabalis, variation in shell color has remained stable for years, but the mechanisms responsible are unknown. Previous studies suggest that this stability could be caused by frequency-dependent sexual selection, but this hypothesis has not been tested. We analyzed shell color polymorphism in mating pairs and surrounding unmated individuals in two different populations of L. fabalis to estimate sexual fitness for color, as well as assortative mating. The estimated effective population size from neutral markers allowed us to disregard genetic drift as the main source of color frequency changes across generations. Shell color frequency was significantly correlated with sexual fitness showing a pattern of negative frequency dependent selection with high disassortative mating for color. The results suggested a contribution of male mate choice to maintain the polymorphism. Finally, the implementation of a multi-model inference approach based on information theory allowed us to test for the relative contribution of mate choice and mate competition to explain the maintenance of color polymorphism in this snail species.
Microbial Signatures in Deep CO2-Saturated Miocene Sediments of the Active Hartoušov Mofette System (NW Czech Republic)
Authors: Liu Qi , Adler Karsten , Lipus Daniel , Kämpf Horst , Bussert Robert , Plessen Birgit , Schulz Hans-Martin , Krauze Patryk , Horn Fabian , Wagner Dirk , Mangelsdorf Kai , Alawi Mashal
Published: December 2020

The Hartoušov mofette system is a natural CO2 degassing site in the central Cheb Basin (Eger Rift, Central Europe). In early 2016 a 108 m deep core was obtained from this system to investigate the impact of ascending mantle-derived CO2 on indigenous deep microbial communities and their surrounding life habitat. During drilling, a CO2 blow out occurred at a depth of 78.5 meter below surface (mbs) suggesting a CO2 reservoir associated with a deep low-permeable CO2-saturated saline aquifer at the transition from Early Miocene terrestrial to lacustrine sediments. Past microbial communities were investigated by hopanoids and glycerol dialkyl glycerol tetraethers (GDGTs) reflecting the environmental conditions during the time of deposition rather than showing a signal of the current deep biosphere. The composition and distribution of the deep microbial community potentially stimulated by the upward migration of CO2 starting during Mid Pleistocene time was investigated by intact polar lipids (IPLs), quantitative polymerase chain reaction (qPCR), and deoxyribonucleic acid (DNA) analysis. The deep biosphere is characterized by microorganisms that are linked to the distribution and migration of the ascending CO2-saturated groundwater and the availability of organic matter instead of being linked to single lithological units of the investigated rock profile. Our findings revealed high relative abundances of common soil and water bacteria, in particular the facultative, anaerobic and potential iron-oxidizing Acidovorax and other members of the family Comamonadaceae across the whole recovered core. The results also highlighted the frequent detection of the putative sulfate-oxidizing and CO2-fixating genus Sulfuricurvum at certain depths. A set of new IPLs are suggested to be indicative for microorganisms associated to CO2 accumulation in the mofette system.