bluuebunny/crossref_metadata_2025 huggingface dataset:
LncRNAs: Architectural Scaffolds or More Potential Roles in Phase Separation
Authors: Luo Jie , Qu Lei , Gao Feiran , Lin Jun , Liu Jian , Lin Aifu
Published: March 2021

Biomolecules specifically aggregate in the cytoplasm and nucleus, driving liquid-liquid phase separation (LLPS) formation and diverse biological processes. Extensive studies have focused on revealing multiple functional membraneless organelles in both the nucleus and cytoplasm. Condensation compositions of LLPS, such as proteins and RNAs affecting the formation of phase separation, have been gradually unveiled. LncRNAs possessing abundant second structures usually promote phase separation formation by providing architectural scaffolds for diverse RNAs and proteins interaction in both the nucleus and cytoplasm. Beyond scaffolds, lncRNAs may possess more diverse functions, such as functioning as enhancer RNAs or buffers. In this review, we summarized current studies on the function of phase separation and its related lncRNAs, mainly in the nucleus. This review will facilitate our understanding of the formation and function of phase separation and the role of lncRNAs in these processes and related biological activities. A deeper understanding of the formation and maintaining of phase separation will be beneficial for disease diagnosis and treatment.
microRNA-210 and microRNA-3570 Negatively Regulate NF-κB-Mediated Inflammatory Responses by Targeting RIPK2 in Teleost Fish
Authors: Su Hui , Chang Renjie , Zheng Weiwei , Sun Yuena , Xu Tianjun
Published: March 2021

Pathogen infection can cause the production of inflammatory cytokines, which are key mediators that cause the host’s innate immune response. Therefore, proper regulation of immune genes associated with inflammation is essential for immune response. Among them, microRNAs (miRNAs) as gene regulator have been widely reported to be involved in the innate immune response of mammals. However, the regulatory network in which miRNAs are involved in the development of inflammation is largely unknown in lower vertebrates. Here, we identified two miRNAs from miiuy croaker (Miichthys miiuy), miR-210 and miR-3570, which play a negative regulatory role in host antibacterial immunity. We found that the expressions of miR-210 and miR-3570 were significantly upregulated under the stimulation of Gram-negative bacterium vibrio harveyi and LPS (lipopolysaccharide). Induced miR-210 and miR-3570 inhibit inflammatory cytokine production by targeting RIPK2, thereby avoiding excessive inflammation. In particular, we found that miR-210 and miR-3570 negatively regulate antimicrobial immunity by regulating the RIPK2-mediated NF-κB signaling pathway. The collective results indicated that both miRNAs are used as negative feedback regulators to regulate RIPK2-mediated NF-κB signaling pathway and thus play a regulatory role in bacteria-induced inflammatory response.
Case Report: Partial Uniparental Disomy Unmasks a Novel Recessive Mutation in the LYST Gene in a Patient With a Severe Phenotype of Chédiak-Higashi Syndrome
Authors: Boluda-Navarro Mireia , Ibáñez Mariam , Liquori Alessandro , Franco-Jarava Clara , Martínez-Gallo Mónica , Rodríguez-Vega Héctor , Teresa Jaijo , Carreras Carmen , Such Esperanza , Zúñiga Ángel , Colobran Roger , Cervera José Vicente
Published: March 2021

Chédiak-Higashi syndrome (CHS) is a rare autosomal recessive (AR) immune disorder that has usually been associated to missense, nonsense or indels mutations in the LYST gene. In this study, we describe for the first time the case of a CHS patient carrying a homozygous mutation in the LYST gene inherited as a result of a partial uniparental isodisomy (UPiD) of maternal origin. Sanger sequencing of the LYST cDNA and single nucleotide polymorphism (SNP)-arrays were performed to identify the causative mutation and to explain the molecular mechanism of inheritance, respectively. Partial-UPiD leads to a copy neutral loss of heterozygosity (CN-LOH) of the telomeric region of chromosome 1 (1q41q44), unmasking the potential effect of the mutation detected. The mutation (c.8380dupT) is an insertion located in exon 32 of the LYST gene resulting in a premature stop codon and leading to the loss of all the conserved domains at the C-terminal of the LYST protein. This would account for the severe phenotype observed. We also reviewed the only two previously reported cases of CHS as a result of a uniparental disomy. In this study, we show that the combination of different strategies, including the use of SNP-arrays, is pivotal to fine-tune the diagnosis of rare AR disorders, such as CHS. Moreover, this case highlights the relevance of uniparental disomy as a potential mechanism of CHS expression in non-consanguineous families.
Major Histocompatibility Complex Class I-Related Chain A (MICA) Allelic Variants Associate With Susceptibility and Prognosis of Gastric Cancer
Authors: Toledo-Stuardo Karen , Ribeiro Carolina H. , Canals Andrea , Morales Marcela , Gárate Valentina , Rodríguez-Siza Jose , Tello Samantha , Bustamante Marco , Armisen Ricardo , Matthies Douglas J. , Zapata-Torres Gerald , González-Hormazabal Patricio , Molina María Carmen
Published: March 2021

Gastric cancer (GC) is the fifth most prevalent type of cancer worldwide. Gastric tumor cells express MICA protein, a ligand to NKG2D receptor that triggers natural killer (NK) cells effector functions for early tumor elimination.MICAgene is highly polymorphic, thus originating alleles that encode protein variants with a controversial role in cancer. The main goal of this work was to studyMICAgene polymorphisms and their relationship with the susceptibility and prognosis of GC. Fifty patients with GC and 50 healthy volunteers were included in this study. MICA alleles were identified using Sanger sequencing methods. The analysis ofMICAgene sequence revealed 13 MICA sequences and 5 MICA-short tandem repeats (STR) alleles in the studied cohorts We identified MICA*002 (*A9) as the most frequent allele in both, patients and controls, followed by MICA*008 allele (*A5.1). MICA*009/049 allele was significantly associated with increased risk of GC (OR: 5.11 [95% CI: 1.39–18.74],p= 0.014). The analysis of MICA-STR alleles revealed a higher frequency of MICA*A5 in healthy individuals than GC patients (OR = 0.34 [95% CI: 0.12–0.98],p= 0.046). Survival analysis after gastrectomy showed that patients with MICA*002/002 or MICA*002/004 alleles had significantly higher survival rates than those patients bearing MICA*002/008 (p= 0.014) or MICA*002/009 (MICA*002/049) alleles (p= 0.040). The presence of threonine in the position MICA-181 (MICA*009/049 allele) was more frequent in GC patients than controls (p= 0.023). Molecular analysis of MICA-181 showed that the presence of threonine provides greater mobility to the protein than arginine in the same position (MICA*004), which could explain, at least in part, some immune evasion mechanisms developed by the tumor. In conclusion, our findings suggest that the study of MICA alleles is crucial to search for new therapeutic approaches and may be useful for the evaluation of risk and prognosis of GC and personalized therapy.
Benchmarking the Human Leukocyte Antigen Typing Performance of Three Assays and Seven Next-Generation Sequencing-Based Algorithms
Authors: Liu Ping , Yao Minya , Gong Yu , Song Yunjie , Chen Yanan , Ye Yizhou , Liu Xiao , Li Fugen , Dong Hua , Meng Rui , Chen Hao , Zheng Aiwen
Published: March 2021

With the great progress made recently in next generation sequencing (NGS) technology, sequencing accuracy and throughput have increased, while the cost for data has decreased. Various human leukocyte antigen (HLA) typing algorithms and assays have been developed and have begun to be used in clinical practice. In this study, we compared the HLA typing performance of three HLA assays and seven NGS-based HLA algorithms and assessed the impact of sequencing depth and length on HLA typing accuracy based on 24 benchmarked samples. The algorithms HISAT-genotype and HLA-HD showed the highest accuracy at both the first field and the second field resolution, followed by HLAscan. Our internal capture-based HLA assay showed comparable performance with whole exome sequencing (WES). We found that the minimal depth was 100X for HISAT-genotype and HLA-HD to obtain more than 90% accuracy at the third field level. The top three algorithms were quite robust to the change of read length. Thus, we recommend using HISAT-genotype and HLA-HD for NGS-based HLA genotyping because of their higher accuracy and robustness to read length. We propose that a minimal sequence depth for obtaining more than 90% HLA typing accuracy at the third field level is 100X. Besides, targeting capture-based NGS HLA typing may be more suitable than WES in clinical practice due to its lower sequencing cost and higher HLA sequencing depth.
Metabolic Reprogramming and Reactive Oxygen Species in T Cell Immunity
Authors: Peng Hao-Yun , Lucavs Jason , Ballard Darby , Das Jugal Kishore , Kumar Anil , Wang Liqing , Ren Yijie , Xiong Xiaofang , Song Jianxun
Published: March 2021

T cells undergo metabolic reprogramming and multiple biological processes to satisfy their energetic and biosynthetic demands throughout their lifespan. Several of these metabolic pathways result in the generation of reactive oxygen species (ROS). The imbalance between ROS generation and scavenging could result in severe damage to the cells and potential cell death, ultimately leading to T cell-related diseases. Interestingly, ROS play an essential role in T cell immunity. Here, we introduce the important connectivity between T cell lifespan and the metabolic reprogramming among distinct T cell subsets. We also discuss the generation and sources of ROS production within T cell immunity as well as highlight recent research concerning the effects of ROS on T cell activities.
Compartments and Connections Within the Germinal Center
Authors: Kennedy Domenick E. , Clark Marcus R.
Published: March 2021

Protective high affinity antibody responses emerge through an orchestrated developmental process that occurs in germinal centers (GCs). While GCs have been appreciated since 1930, a wealth of recent progress provides new insights into the molecular and cellular dynamics governing humoral immunity. In this review, we highlight advances that demonstrate that fundamental GC B cell function, selection, proliferation and SHM occur within distinct cell states. The resulting new model provides new opportunities to understand the evolution of immunity in infectious, autoimmune and neoplastic diseases.
Positive Selection in the Light Zone of Germinal Centers
Authors: Nakagawa Rinako , Calado Dinis Pedro
Published: March 2021

Germinal centers (GCs) are essential sites for the production of high-affinity antibody secreting plasma cells (PCs) and memory-B cells (MBCs), which form the framework of vaccination. Affinity maturation and permissive selection in GCs are key for the production of PCs and MBCs, respectively. For these purposes, GCs positively select “fit” cells in the light zone of the GC and instructs them for one of three known B cell fates: PCs, MBCs and persistent GC-B cells as dark zone entrants. In this review, we provide an overview of the positive selection process and discuss its mechanisms and how B cell fates are instructed.
A Conceptual Framework for Incorporating Human Dimensions Into Integrated Ecosystem Assessments
Authors: Szymkowiak Marysia
Published: March 2021

The evolution of fisheries science and management toward an ecosystem perspective necessitates the meaningful incorporation of human dimensions. Whereas great strides have been made over the last several decades at moving toward ecosystem based fisheries management (EBFM), largely through the development of integrated ecosystem assessments (IEAs), the inclusion of human dimensions into these efforts has often been fragmentary and, in juxtaposition to the biophysical dynamics, sometimes even seemingly superficial. This presents a great challenge to the accuracy and applicability of these results, as the lack of appropriate incorporation of humans can be problematic in terms of both social and biophysical consequences. This study systematically documents current social science understanding of the multiple human dimensions that should be incorporated within ecosystem assessments and the overall approach to each of these within IEAs and other EBFM efforts. These dimensions include the multi-faceted nature of human well-being, heterogeneity in human well-being derived from fisheries, adaptive behaviors, and cumulative effects. The systematic inclusion of these dimensions into IEAs is then laid out in a conceptual framework that details how a perturbation reverberates through a fisheries system and the iterative approach that should be undertaken to understand its impacts on human dimensions. This framework is supplemented with a data collection scheme that is intended to facilitate operationalization. The detailed examination of incorporating human dimensions within IEAs presented in this study should further resonate with other ecosystem assessment efforts, providing not just ample evidence of the need for moving beyond simplistic assumptions of human homogeneity but a means of systematically integrating a more realistic and representative perspective.
Impact of Intercropping on the Diazotrophic Community in the Soils of Continuous Cucumber Cropping Systems
Authors: Gao Huan , Li Sen , Wu Fengzhi
Published: March 2021

Diazotrophs are important soil components that help replenish biologically available nitrogen (N) in the soil and contribute to minimizing the use of inorganic N fertilizers in agricultural ecosystems. However, there is little understanding of how diazotrophs respond to intercropping and soil physicochemical properties in cucumber continuous cropping systems. In this study, using the nifH gene as a marker, we have examined the impacts of seven intercropping plants on diazotrophic community diversity and composition compared to a cucumber continuous cropping system during two cropping seasons. The results showed that intercropping increased the abundance of the nifH gene, which was negatively correlated with available phosphorous in the fall. Diazotrophic diversity and richness were higher in the rape–cucumber system than in the monoculture. Multivariate regression tree analysis revealed that the diversity of the diazotrophic communties was shaped mainly by soil moisture and available phosphorous. Skermanella were the dominant genera in all of the samples, which increased significantly in the mustard–cucumber system in the fall. There was no effect of intercropping on the structure of the diazotrophic community in this case. Non-metric multidimensional scaling analysis showed that cropping season had a greater effect than intercropping on the community structure of the diazotrophs. Overall, our results suggest that intercropping altered the abundance and diversity rather than the structure of the diazotrophic community, which may potentially affect the N fixation ability of continuous cropping systems.
Unique Brewing-Relevant Properties of a Strain of Saccharomyces jurei Isolated From Ash (Fraxinus excelsior)
Authors: Hutzler Mathias , Michel Maximilian , Kunz Oliver , Kuusisto Tiina , Magalhães Frederico , Krogerus Kristoffer , Gibson Brian
Published: March 2021

The successful application of Saccharomyces eubayanus and Saccharomyces paradoxus in brewery fermentations has highlighted the potential of wild Saccharomyes yeasts for brewing, and prompted investigation into the application potential of other members of the genus. Here, we evaluate, for the first time, the brewing potential of Saccharomyces jurei. The newly isolated strain from an ash tree (Fraxinus excelsior) in Upper Bavaria, Germany, close to the river Isar, was used to ferment a 12°P wort at 15°C. Performance was compared directly with that of a reference lager strain (TUM 34/70) and the S. eubayanus type strain. Both wild yeast rapidly depleted simple sugars and thereafter exhibited a lag phase before maltose utilization. This phase lasted for 4 and 10 days for S. eubayanus and S. jurei, respectively. S. eubayanus utilized fully the available maltose but, consistent with previous reports, did not use maltotriose. S. jurei, in contrast, utilized approximately 50% of the maltotriose available, making this the first report of maltotriose utilization in a wild Saccharomyces species. Maltotriose use was directly related to alcohol yield with 5.5, 4.9, and 4.5% ABV produced by Saccharomyces pastorianus, S. jurei, and S. eubayanus. Beers also differed with respect to aroma volatiles, with a high level (0.4 mg/L) of the apple/aniseed aroma ethyl hexanoate in S. jurei beers, while S. eubayanus beers had a high level of phenylethanol (100 mg/L). A trained panel rated all beers as being of high quality, but noted clear differences. A phenolic spice/clove note was prominent in S. jurei beer. This was less pronounced in the S. eubayanus beers, despite analytical levels of 4-vinylguaiacol being similar. Tropical fruit notes were pronounced in S. jurei beers, possibly resulting from the high level of ethyl hexanoate. Herein, we present results from the first intentional application of S. jurei as a yeast for beer fermentation (at the time of submission) and compare its fermentation performance to other species of the genus. Results indicate considerable potential for S. jurei application in brewing, with clear advantages compared to other wild Saccharomyces species.
Glycated Hemoglobin as a Marker for Predicting Outcomes of Patients With Stroke (Ischemic and Hemorrhagic): A Systematic Review and Meta-Analysis
Authors: Bao Yaya , Gu Dadong
Published: March 2021

Background: Glycated hemoglobin (HbA1c) has emerged as a useful biochemical marker reflecting the average glycemic control over the last 3 months, and the values are not affected by short-term transient changes in blood glucose levels. However, its prognostic value in the acute neurological conditions such as stroke is still not well-established. The present meta-analysis was conducted to assess the relationship of HbA1c with outcomes such as mortality, early neurological complications, and functional dependence in stroke patients.

Methods: A systematic search was conducted for the PubMed, Scopus, and Google Scholar databases. Studies, either retrospective or prospective in design that examined the relationship between HbA1c with outcomes of interest and presented the strength of association in the form of adjusted odds ratio/hazard ratios were included in the review. Statistical analysis was done using STATA version 13.0.

Results: A total of 22 studies (15 studies on acute ischemic stroke and seven studies on hemorrhagic stroke) were included in the meta-analysis. For patients with acute ischemic stroke, each unit increase in HbA1c was found to be associated with an increased risk of mortality within 1 year, increased risk of poor functional outcome at 3 months, and an increased risk of symptomatic intracranial hemorrhage (sICH) within 24 h of admission. In those with HbA1c ≥ 6.5%, there was an increased risk of mortality within 1 year of admission, increased risk of poor functional outcomes at 3 and 12 months as well as an increased risk of symptomatic intracranial hemorrhage (sICH) within 24 h of admission. In patients with hemorrhagic stroke, each unit increase in HbA1c was found to be associated with increased risk of poor functional outcome within the first 3 months from the time of admission for stroke. In those with HbA1c ≥ 6.5%, there was an increased risk of poor functional outcome at 12 months.

Conclusions: The findings indicate that glycated hemoglobin (HbA1c) could serve as a useful marker to predict the outcomes in patients with stroke and aid in the implementation of adequate preventive management strategies at the earliest.
Cellular Composition of the Preoptic Area Regulating Sleep, Parental, and Sexual Behavior
Authors: Tsuneoka Yousuke , Funato Hiromasa
Published: March 2021

The preoptic area (POA) has long been recognized as a sleep center, first proposed by von Economo. The POA, especially the medial POA (MPOA), is also involved in the regulation of various innate functions such as sexual and parental behaviors. Consistent with its many roles, the MPOA is composed of subregions that are identified by different gene and protein expressions. This review addresses the current understanding of the molecular and cellular architecture of POA neurons in relation to sleep and reproductive behavior. Optogenetic and pharmacogenetic studies have revealed a diverse group of neurons within the POA that exhibit different neural activity patterns depending on vigilance states and whose activity can enhance or suppress wake, non-rapid eye movement (NREM) sleep, or rapid eye movement (REM) sleep. These sleep-regulating neurons are not restricted to the ventrolateral POA (VLPO) region but are widespread in the lateral MPOA and LPOA as well. Neurons expressing galanin also express gonadal steroid receptors and regulate motivational aspects of reproductive behaviors. Moxd1, a novel marker of sexually dimorphic nuclei (SDN), visualizes the SDN of the POA (SDN-POA). The role of the POA in sleep and other innate behaviors has been addressed separately; more integrated observation will be necessary to obtain physiologically relevant insight that penetrates the different dimensions of animal behavior.
SOX Transcription Factors as Important Regulators of Neuronal and Glial Differentiation During Nervous System Development and Adult Neurogenesis
Authors: Stevanovic Milena , Drakulic Danijela , Lazic Andrijana , Ninkovic Danijela Stanisavljevic , Schwirtlich Marija , Mojsin Marija
Published: March 2021

The SOX proteins belong to the superfamily of transcription factors (TFs) that display properties of both classical TFs and architectural components of chromatin. Since the cloning of theSox/SOXgenes, remarkable progress has been made in illuminating their roles as key players in the regulation of multiple developmental and physiological processes. SOX TFs govern diverse cellular processes during development, such as maintaining the pluripotency of stem cells, cell proliferation, cell fate decisions/germ layer formation as well as terminal cell differentiation into tissues and organs. However, their roles are not limited to development since SOX proteins influence survival, regeneration, cell death and control homeostasis in adult tissues. This review summarized current knowledge of the roles of SOX proteins in control of central nervous system development. Some SOX TFs suspend neural progenitors in proliferative, stem-like state and prevent their differentiation. SOX proteins function as pioneer factors that occupy silenced target genes and keep them in a poised state for activation at subsequent stages of differentiation. At appropriate stage of development, SOX members that maintain stemness are down-regulated in cells that are competent to differentiate, while other SOX members take over their functions and govern the process of differentiation. Distinct SOX members determine down-stream processes of neuronal and glial differentiation. Thus, sequentially acting SOX TFs orchestrate neural lineage development defining neuronal and glial phenotypes. In line with their crucial roles in the nervous system development, deregulation of specific SOX proteins activities is associated with neurodevelopmental disorders (NDDs). The overview of the current knowledge about the link betweenSOXgene variants and NDDs is presented. We outline the roles of SOX TFs in adult neurogenesis and brain homeostasis and discuss whether impaired adult neurogenesis, detected in neurodegenerative diseases, could be associated with deregulation of SOX proteins activities. We present the current data regarding the interaction between SOX proteins and signaling pathways and microRNAs that play roles in nervous system development. Finally, future research directions that will improve the knowledge about distinct and various roles of SOX TFs in health and diseases are presented and discussed.
B7 Family Members in Lymphoma: Promising Novel Targets for Tumor Immunotherapy?
Authors: Zhang Wei , Qiu Yu , Xie Xiaoli , Fu Yao , Wang Lijuan , Cai Zhen
Published: March 2021

T cells play a vital role in the immune responses against tumors. Costimulatory or coinhibitory molecules regulate T cell activation. Immune checkpoint inhibitors, such as programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) have shown remarkable benefits in patients with various tumor, but few patients have displayed significant immune responses against tumors after PD-1/PD-L1 immunotherapy and many have been completely unresponsive. Thus, researchers must explore novel immune checkpoints that trigger durable antitumor responses and improve clinical outcomes. In this regard, other B7 family checkpoint molecules have been identified, namely PD-L2, B7-H2, B7-H3, B7-H4 and B7-H6. The aim of the present article was to address the expression, clinical significance and roles of B7 family molecules in lymphoma, as well as in T and NK cell-mediated tumor immunity. B7 family checkpoints may offer novel and immunotherapeutic strategies for patients with lymphoma.
The Accuracy of Individualized 3D-Printing Template-Assisted I125 Radioactive Seed Implantation for Recurrent/Metastatic Head and Neck Cancer
Authors: Qiu Bin , Jiang Yuliang , Ji Zhe , Sun Haitao , Fan Jinghong , Li Weiyan , Shao Yuxia , Jiang Ping , Wang Junjie
Published: March 2021

Purpose

To evaluate the accuracy of individualized 3D-printing template-assisted I125 radioactive seed implantation (3D-PT assisted I125 RSI) for recurrent/metastatic head and neck cancer.

Materials and Methods

From February 2017 to January 2020, clinical data of 41 patients (mean age, 58.5 ± 16.1 years; 28 males) with recurrent (48.8%)/metastatic (51.2%) head and neck cancer underwent individualized 3D-PT assisted I125 RSI under CT guidance in a single institute were retrospectively reviewed. Total 430 seed needles [mean, 10.5 (range 3–17) per patient] were inserted.

Results

All seed needles were inserted manually in a single attempt with the technical success rate of 100% without major perioperative complications. The mean needle’s entrance deviation was 0.090 cm (95% Confidence Interval, 0.081–0.098). The mean intraoperative depth and angle of the needle were consistent with that of planned (6.23 ± 0.24 vs. 6.21 ± 0.24 cm, p = 0.903; 83.14 ± 3.64 vs. 83.09 ± 3.66 degrees, p = 0.985, respectively). The mean deviation between the needle’s planned and intraoperative depth and angle was 0.168 ± 0.024 cm and 1.56 ± 0.14 degrees, respectively. The postoperative dosimetry parameters, including D90, D100, V100, V150, V200, conformity index, external index, and homogeneity index, were all well-coordinated with planned dosimetry without significant difference (p = 0.515, 0.662, 0.958, 0.865, 0.872, 0.278, 0.456, and 0.989, respectively).

Conclusions

Within the limitation of this study, individualized 3D-PT assisted I125 RSI may be accurate in obtaining favorable postoperative dosimetry for patients with recurrent/metastatic head and neck cancer.

Clinical Trial Registration

[website], identifier [registration number].
Type I Interferonopathies in Children: An Overview
Authors: d'Angelo Debora M. , Di Filippo Paola , Breda Luciana , Chiarelli Francesco
Published: March 2021

Notable advances in gene sequencing methods in recent years have permitted enormous progress in the phenotypic and genotypic characterization of autoinflammatory syndromes. Interferonopathies are a recent group of inherited autoinflammatory diseases, characterized by a dysregulation of the interferon pathway, leading to constitutive upregulation of its activation mechanisms or downregulation of negative regulatory systems. They are clinically heterogeneous, but some peculiar clinical features may lead to suspicion: a familial “idiopathic” juvenile arthritis resistant to conventional treatments, an early necrotizing vasculitis, a non-infectious interstitial lung disease, and a panniculitis associated or not with a lipodystrophy may represent the “interferon alarm bells.” The awareness of this group of diseases represents a challenge for pediatricians because, despite being rare, a differential diagnosis with the most common childhood rheumatological and immunological disorders is mandatory. Furthermore, the characterization of interferonopathy molecular pathogenetic mechanisms is allowing important steps forward in other immune dysregulation diseases, such as systemic lupus erythematosus and inflammatory myositis, implementing the opportunity of a more effective target therapy.
Management of Vesicoureteral Reflux: What Have We Learned Over the Last 20 Years?
Authors: Läckgren Göran , Cooper Christopher S. , Neveus Tryggve , Kirsch Andrew J.
Published: March 2021

Vesicoureteral reflux (VUR) is associated with increased risks of urinary tract infection, renal scarring and reflux nephropathy. We review advancements over the last two decades in our understanding and management of VUR. Over time, the condition may resolve spontaneously but it can persist for many years and bladder/bowel dysfunction is often involved. Some factors that increase the likelihood of persistence (e.g., high grade) also increase the risk of renal scarring. Voiding cystourethrography (VCUG) is generally considered the definitive method for diagnosing VUR, and helpful in determining the need for treatment. However, this procedure causes distress and radiation exposure. Therefore, strategies to reduce clinicians' reliance upon VCUG (e.g., after a VUR treatment procedure) have been developed. There are several options for managing patients with VUR. Observation is suitable only for patients at low risk of renal injury. Antibiotic prophylaxis can reduce the incidence of UTIs, but drawbacks such as antibiotic resistance and incomplete adherence mean that this option is not viable for long-term use. Long-term studies of endoscopic injection have helped us understand factors influencing use and the effectiveness of this procedure. Ureteral reimplantation is still performed commonly, and robot-assisted laparoscopic methods are gaining popularity. Over the last 20 years, there has been a shift toward more conservative management of VUR with an individualized, risk-based approach. For continued treatment improvement, better identification of children at risk of renal scarring, robust evidence regarding the available interventions, and an improved VUR grading system are needed.
Changing Patient and Public Beliefs About Antimicrobials and Antimicrobial Resistance (AMR) Using a Brief Digital Intervention
Authors: Chan Amy Hai Yan , Horne Rob , Lycett Helen , Raebel Eva , Guitart Jordi , Wildman Emilie , Ang Karen
Published: March 2021

Background: A key driver of antimicrobial resistance (AMR) is patient demand for unnecessary antibiotics, which is driven by patients’ beliefs about antibiotics and AMR. Few interventions have targeted beliefs to reduce inappropriate demand.

Objective: To examine whether a brief, online algorithm-based intervention can change beliefs that may lead to inappropriate antibiotic demand (i.e. perceptions of antibiotic necessity and lack of concern about antibiotic harm).

Design: Pre- and post-intervention study.

Participants: Participants were 18 years or older, and residing in the United Kingdom, who self-selected to participate via Amazon mTurk, an online survey plaform, and via research networks.

Intervention: Participants were presented with a hypothetical situation of cold and flu symptoms, then exposed to the intervention. The online intervention comprised: 1) a profiling tool identifying individual beliefs (antibiotic necessity, concerns, and knowledge) driving inappropriate antibiotic demand; 2) messages designed to change beliefs and knowledge (i.e. reduce antibiotic necessity, and increase antibiotic concerns and knowledge), and 3) an algorithm linking specific messages to specific beliefs and knowledge.

Main measures: The profiling tool was repeated immediately after the intervention and compared with baseline scores to assess change in beliefs. A paired samples t-test was used to determine intervention effect.

Key Results: A total of 100 respondents completed the study. A significant change in beliefs relating to inappropriate demand was observed after the intervention, with a reduction in beliefs about antibiotic necessity (t = 7.254; p < 0.0001), an increase in antibiotic concerns (t = −7.214; p < 0.0001), and increases in antibiotic and AMR knowledge (t = −4.651; p < 0.0001).

Conclusion: This study is the first to demonstrate that patient beliefs about antibiotics and AMR associated with inappropriate demand can be changed by a brief, tailored online intervention. This has implications for the design of future interventions to reduce unnecessary antimicrobial use.
Characterization of Chicken Skin Yellowness and Exploration of Genes Involved in Skin Yellowness Deposition in Chicken
Authors: Wu Jingwen , Lin Zetong , Chen Genghua , Luo Qingbin , Nie Qinghua , Zhang Xiquan , Luo Wen
Published: March 2021

Skin color is an important economic trait in meat-type chickens. A uniform bright skin color can increase the sales value of chicken. Chickens with bright yellow skin are more popular in China, especially in the broiler market of South China. However, the skin color of chickens can vary because of differences in breeds, diet, health, and individual genetics. To obtain greater insight into the genetic factors associated with the process of skin pigmentation in chickens, we used a colorimeter and high-resolution skin photographs to measure and analyze the skin color of chickens. By analyzing 534 chickens of the same breed, age, and feed condition, we found that the yellowness values of the chickens varied within this population. A significant positive correlation was found between the cloacal skin yellowness values before and after slaughter, and the cloacal skin yellowness value of live chickens was positively correlated with the overall body skin yellowness value. Additionally, chicken skin yellowness exhibited low heritability, ranging from 0.07 to 0.27. Through RNA sequencing, 882 genes were found to be differentially expressed between the skin with the highest and lowest yellowness values. Some of these differentially expressed genes may play an important role in yellow pigment deposition in chicken skin, which included TLR2B, IYD, SMOC1, ALDH1A3, CYP11A1, FHL2, TECRL, ACACB, TYR, PMEL, and GPR143. In addition, we found that the expression and variations of the BCO2 gene, which is referred to as the yellow skin gene, cannot be used to estimate the skin yellowness value of chickens in this population. These data will help to further our understanding of chicken skin yellowness and might contribute to the selection of specific chicken strains with consistent skin coloration.
Power Amplification Increases With Contraction Velocity During Stretch-Shortening Cycles of Skinned Muscle Fibers
Authors: Tomalka André , Weidner Sven , Hahn Daniel , Seiberl Wolfgang , Siebert Tobias
Published: March 2021

Muscle force, work, and power output during concentric contractions (active muscle shortening) are increased immediately following an eccentric contraction (active muscle lengthening). This increase in performance is known as the stretch-shortening cycle (SSC)-effect. Recent findings demonstrate that the SSC-effect is present in the sarcomere itself. More recently, it has been suggested that cross-bridge (XB) kinetics and non-cross-bridge (non-XB) structures (e.g., titin and nebulin) contribute to the SSC-effect. As XBs and non-XB structures are characterized by a velocity dependence, we investigated the impact of stretch-shortening velocity on the SSC-effect. Accordingly, we performedin vitroisovelocity ramp experiments with varying ramp velocities (30, 60, and 85% of maximum contraction velocity for both stretch and shortening) and constant stretch-shortening magnitudes (17% of the optimum sarcomere length) using single skinned fibers of rat soleus muscles. The different contributions of XB and non-XB structures to force production were identified using the XB-inhibitor Blebbistatin. We show that (i) the SSC-effect is velocity-dependent—since the power output increases with increasing SSC-velocity. (ii) The energy recovery (ratio of elastic energy storage and release in the SSC) is higher in the Blebbistatin condition compared with the control condition. The stored and released energy in the Blebbistatin condition can be explained by the viscoelastic properties of the non-XB structure titin. Consequently, our experimental findings suggest that the energy stored in titin during the eccentric phase contributes to the SSC-effect in a velocity-dependent manner.
Association of Metabolic Syndrome With Prevalence of Obstructive Sleep Apnea and Remission After Sleeve Gastrectomy
Authors: Chen Yufei , Chen Lijia , Ye Lingxia , Jin Jiabin , Sun Yingkai , Zhang Ling , Zhao Shaoqian , Zhang Yifei , Wang Weiqing , Gu Weiqiong , Hong Jie
Published: March 2021

Obesity is an important risk factor for metabolic syndrome and obstructive sleep apnea (OSA). Bariatric surgery has been shown to effectively reduce weight and obesity-related comorbidities. However, the prevalence and severity of OSA in obese patients with different baseline metabolic states and the improvements of OSA after bariatric surgery remain unknown. The main aims of this study were to ascertain the prevalence of OSA in young Chinese obese patients with different metabolic states and to evaluate their respective OSA remission after laparoscopic sleeve gastrectomy. We first performed a cross-sectional study involving 123 metabolically healthy obese patients and 200 metabolically unhealthy obese patients (who had the same age and BMI ranges) to estimate the prevalence of OSA at baseline. Then we performed a retrospective study, which was registered at ClinicalTrials.gov (ref. NCT02653430) of 67 patients who underwent laparoscopic sleeve gastrectomy to evaluate the remission of OSA. Metabolically healthy and unhealthy obese patients had similar apnea-hypopnea index levels (16.6 ± 22.0 vs. 16.7 ± 18.7 events/h, P = 0.512) and prevalence of OSA (66.7% vs. 69.0%, P = 0.662). Male sex, age, waist circumference and lower liver-to-spleen ratio were independent risk factors for OSA. After laparoscopic sleeve gastrectomy, no difference was found in the decrease in body mass index (BMI) change (10.8 ± 4.8 vs. 10.8 ± 3.0 kg/m2, P = 0.996) or the decrease in the apnea-hypopnea index (18.9 ± 24.6 vs. 17.0 ± 24.0 events/h, P = 0.800). The remission of moderate-to-severe OSA was observed in the MHO (36.3%; 54.5–18.2%, P = 0.125) and MUO (32.2%; 66.1–33.9%, P = 0.001) patients. These results suggest that, in patients with obesity, metabolic syndrome does not add extra risk for the prevalence or severity of OSA. Both metabolically healthy and unhealthy obese patients could benefit equally from laparoscopic sleeve gastrectomy in terms of weight loss and obstructive sleep apnea remission.
Confirmation of a Gametophytic Self-Incompatibility in Oryza longistaminata
Authors: Lian Xiaoping , Zhang Shilai , Huang Guangfu , Huang Liyu , Zhang Jing , Hu Fengyi
Published: March 2021

Oryza longistaminata, a wild species of African origin, has been reported to exhibit self-incompatibility (SI). However, the genetic pattern of its SI remained unknown. In this study, we conducted self-pollination and reciprocal cross-pollination experiments to verify that O. longistaminata is a strictly self-incompatible species. The staining of pollen with aniline blue following self-pollination revealed that although pollen could germinate on the stigma, the pollen tube was unable to enter the style to complete pollination, thereby resulting in gametophytic self-incompatibility (GSI). LpSDUF247, a S-locus male determinant in the gametophytic SI system of perennial ryegrass, is predicted to encode a DUF247 protein. On the basic of chromosome alignment with LpSDUF247, we identified OlSS1 and OlSS2 as Self-Incompatibility Stamen candidate genes in O. longistaminata. Chromosome segment analysis revealed that the Self-Incompatibility Pistil candidate gene of O. longistaminata (OlSP) is a polymorphic gene located in a region flanking OlSS1. OlSS1 was expressed mainly in the stamens, whereas OlSS2 was expressed in both the stamens and pistils. OlSP was specifically highly expressed in the pistils, as revealed by RT-PCR and qRT-PCR analyses. Collectively, our observations indicate the occurrence of GSI in O. longistaminata and that this process is potentially controlled by OlSS1, OlSS2, and OlSP. These findings provide further insights into the genetic mechanisms underlying self-compatibility in plants.
Comparing a Mixed Model Approach to Traditional Stability Estimators for Mapping Genotype by Environment Interactions and Yield Stability in Soybean [Glycine max (L.) Merr.]
Authors: Happ Mary M. , Graef George L. , Wang Haichuan , Howard Reka , Posadas Luis , Hyten David L.
Published: March 2021

Identifying genetic loci associated with yield stability has helped plant breeders and geneticists begin to understand the role and influence of genotype by environment (GxE) interactions in soybean [Glycine max (L.) Merr.] productivity, as well as other crops. Quantifying a genotype’s range of performance across testing locations has been developed over decades with dozens of methodologies available. This includes directly modeling GxE interactions as part of an overall model for yield, as well as methods which generate overall yield “stability” values from multi-environment trial data. Correspondence between these methods as it pertains to the outcomes of genome wide association studies (GWAS) has not been well defined. In this study, the GWAS results for yield and yield stability were compared in 213 soybean lines across 11 environments to determine their utility and potential intersection. Both univariate and multivariate conventional stability estimates were considered alongside a mixed model for yield that fit marker by environment interactions as a random effect. One-hundred and six total QTL were discovered across all mapping results, however, genetic loci that were significant in the mixed model for grain yield that fit marker by environment interactions were completely distinct from those that were significant when mapping using traditional stability measures as a phenotype. Furthermore, 73.21% of QTL discovered in the mixed model were determined to cause a crossover interaction effect which cause genotype rank changes between environments. Overall, the QTL discovered via explicitly mapping GxE interactions also explained more yield variance that those QTL associated with differences in traditional stability estimates making their theoretical impact on selection greater. A lack of intersecting results between mapping approaches highlights the importance of examining stability in multiple contexts when attempting to manipulate GxE interactions in soybean.
Evolution of Bird and Insect Flower Traits in Fritillaria L. (Liliaceae)
Authors: Roguz Katarzyna , Hill Laurence , Roguz Agata , Zych Marcin
Published: March 2021

Pollinators are often perceived as a primary selective agent influencing flower traits such as colour, size, and nectar properties. The genus Fritillaria L. (Liliaceae), comprising approximately 150 species, is described as generally insect pollinated. However, there are at least three exceptions: two hummingbird-pollinated North American species and one passerine-pollinated Asian species. Despite this variation in pollination, little is known about flower traits that may accompany this shift in fritillaries. In this study, we aimed to assess the attractiveness of the floral traits for (new) pollinators and track the evolution of flowers traits in the context of a shift in the principal pollinator. Therefore, we studied 14 flower traits related to the pollination in 60 Fritillaria species and traced the evolutionary trajectory of these traits. We used a phylogenetic tree of the genus, based on five DNA markers (matK, rpl16, and rbcL, 18S, and ITS) to reconstruct the ancestral state of studied flower traits. The results show that in bird-pollinated species several new traits evolved. For example, flower colouration, nectar sugar, and amino acid concentration and composition fulfil the criteria of ornithophilous flowers, although flower traits do not exclude insect pollinators in bird-pollinated fritillaries. Interestingly, we recorded potential reversals from bird to insect pollination. Our analysis, showing a broad study of flower traits among closely related species in the context of pollinator shift, serves as a starting point for future work exploring the genetic and physiological mechanisms controlling flower traits in the genus Fritillaria.
Is Anyone Representing Non-resident Finnish Citizens in the Legislative Process of Finland?
Authors: Makkonen Kimmo
Published: March 2021

This research paper examines the instances of representation of the expatriate Finnish citizen in the different stages of the legislative process in Finland: the preparation of law bills, the process in the Parliamentary committees and in the plenary sessions of the Finnish Parliament Eduskunta. The aim is to answer the questions how many and what kind of expatriate Finns issues there has been on the political agenda, when those issues were there, and who acted for the expatriates then. Here, the research approach is descriptive. Newly digitalized collections of legislative documents create novel opportunities to seek efficiently through a large number of records and find topics that have not gained much attention, in addition to the more obvious cases such as the dual citizenship or recently the postal voting. In Finland, the Finnish diaspora has not been a fervently debated issue and it is only rarely mentioned in the plenary debates of the Parliament. The data includes two kinds of sources, actions by the MPs and Government bills. In the Finnish case, the number of relevant documents is small. Therefore, including different types of text into a single study is necessary to find out the political forces that have influence on the issues concerning the Finnish citizen abroad.
How E-Learning Environmental Stimuli Influence Determinates of Learning Engagement in the Context of COVID-19? SOR Model Perspective
Authors: Yang Junhui , Peng Michael Yao-Ping , Wong ShwuHuey , Chong WeiLoong
Published: March 2021

The COVID-19 pandemic at the beginning of 2020 has changed the conventional learning mode for most students at schools all over the world, and the e-learning at home has become a new trend. Taking Chinese college students as the research subject and drawing on the stimulus–organism–response (S-O-R) model, this paper examines the relationship between the peer referent, perceived closeness, and perceived control and the learning engagement. Using data from 377 college students who have used e-learning, this study shows that perceived closeness, perceived control, and peer referents in e-learning have a positive effect on the self-efficacy and well-being of students, thus improving students’ enthusiasm for learning. Our intent is to assist researchers, instructors, designers, and others in identifying effective methods to conceptualize and measure student engagement in e-learning.