bluuebunny/crossref_metadata_2025 huggingface dataset:
Parasite-Modified Chemical Communication: Implications for Aquatic Community Dynamics
Authors: Friesen Olwyn C. , Detwiler Jillian T.
Published: March 2021

Chemical communication within an aquatic environment creates an intricate signaling web that provides species with information about their surroundings. Signaling molecules, like oxylipins, mediate a multitude of interactions between free-living members of a community including non-consumptive effects by predators. Parasites are another source of signaling molecules in aquatic communities and contribute directly by synthesizing them or indirectly by manipulating host chemical cues. If chemical cues of infected hosts are altered, then non-consumptive interactions between other members of the community may also be affected. Different cues from infected hosts may alter behaviors in other individuals related to foraging, competition, and defense priming. Here, we discuss how parasites could modify host chemical cues, which may have far reaching consequences for other community members and the ecosystem. We discuss how the modification of signaling molecules by parasites may also represent a mechanism for parasite-modified behavior within some systems and provide a mechanism for non-consumptive effects of parasites. Further, we propose a host-parasite system that could be used to investigate some key, unanswered questions regarding the relationship between chemical cues, parasite-modified behavior, and non-consumptive effects. We explain how trematode-gastropod systems can be used to test whether there are alterations in the diversity and amounts of signaling molecules available, and if habitat use, immune function, and behavior of other individuals and species are affected. Finally, we argue that changes to pathway crosstalk by parasites within communities may have broad ecological implications.
Light Intensity Influence on Growth and Photosynthetic Characteristics of Horsfieldia hainanensis
Authors: Wang Xin , Chen Guode , Du Shangjia , Wu Haixia , Fu Rong , Yu Xuebiao
Published: March 2021

Due to both anthropogenic and natural causes, the number of Horsfieldia hainanensis has been decreasing each year in the Tongza Branch nursery (109.534 525°E, 18.763 516°N) of the Hainan Academy of Forestry, China. Consequently, the protection of H. hainanensis is urgent, as is that of most rare tree species. To develop a more comprehensive understanding of the H. hainanensis growth environment, we took 3-year-old H. hainanensis saplings as the research object. We controlled the light intensity by setting different shade amounts to explore the growth and photosynthetic characteristics of H. hainanensis under different light intensities. We found that shade can promote growth and increase the contents of certain substances. Light transmittance of 44.41% can increase plant height (by 29.545%) and biomass (by 66.676%). Light transmittance of 16.19% can increase the pigment content; Chl increased by 40.864%, Chl a increased by 38.031%, and Chl b increased by 48.412%. Light transmittance of 7.30% can increase the soil plant analysis development (SPAD) value of each part of the leaf; the leaf base increased by 41.000%, the leaf margin increased by 32.574%, the blade tip increased by 49.003%, and the leaf average increased by 40.466%. The specific leaf area can reduce the specific leaf weight. We also found that compared to full light, reducing the light transmittance can increase the total chlorophyll (Chl), chlorophyll A (Chl a), and chlorophyll B (Chl b) contents, and the Chl-SPAD-leaf base, leaf edge, leaf tip, average content, and light-saturated net photosynthetic rate. This can in turn reduce the apparent quantum efficiency (AQY), light compensation point (LCP), and dark respiration rate (Rd). In addition, we found a strong correlation between seven of the photosynthetic pigment indicators (Chl, Chla, Chl b, Chl-SPAD-leaf base, leaf margin, leaf tip, and mean) and the three photosynthesis physiological parameters (AQY, LCP, and Rd). The light transmittance of 44.41% (one layer of shading net) treatment group was conducive to the growth of H. hainanensis and photosynthetic characteristic improvement. Therefore, our light transmittance selection of approximately 44.4% is significant for the natural return of H. hainanensis.
Melatonin Attenuates Sepsis-Induced Small-Intestine Injury by Upregulating SIRT3-Mediated Oxidative-Stress Inhibition, Mitochondrial Protection, and Autophagy Induction
Authors: Xu Siqi , Li Lulan , Wu Jie , An Sheng , Fang Haihong , Han Yunyang , Huang Qiaobing , Chen Zhongqing , Zeng Zhenhua
Published: March 2021

Melatonin reportedly alleviates sepsis-induced multi-organ injury by inducing autophagy and activating class III deacetylase Sirtuin family members (SIRT1–7). However, whether melatonin attenuates small-intestine injury along with the precise underlying mechanism remain to be elucidated. To investigate this, we employed cecal ligation and puncture (CLP)- or endotoxemia-induced sepsis mouse models and confirmed that melatonin treatment significantly prolonged the survival time of mice and ameliorated multiple-organ injury (lung/liver/kidney/small intestine) following sepsis. Melatonin partially protected the intestinal barrier function and restored SIRT1 and SIRT3 activity/protein expression in the small intestine. Mechanistically, melatonin treatment enhanced NF-κB deacetylation and subsequently reduced the inflammatory response and decreased the TNF-α, IL-6, and IL-10 serum levels; these effects were abolished by SIRT1 inhibition with the selective blocker, Ex527. Correspondingly, melatonin treatment triggered SOD2 deacetylation and increased SOD2 activity and subsequently reduced oxidative stress; this amelioration of oxidative stress by melatonin was blocked by the SIRT3-selective inhibitor, 3-TYP, and was independent of SIRT1. We confirmed this mechanistic effect in a CLP-induced sepsis model of intestinal SIRT3 conditional-knockout mice, and found that melatonin preserved mitochondrial function and induced autophagy of small-intestine epithelial cells; these effects were dependent on SIRT3 activation. This study has shown, to the best of our knowledge, for the first time that melatonin alleviates sepsis-induced small-intestine injury, at least partially, by upregulating SIRT3-mediated oxidative-stress inhibition, mitochondrial-function protection, and autophagy induction.
Taurine Alleviates Streptococcus uberis-Induced Inflammation by Activating Autophagy in Mammary Epithelial Cells
Authors: Wang Zhenglei , Lan Riguo , Xu Yuanyuan , Zuo Jiakun , Han Xiangan , Phouthapane Vanhnaseng , Luo Zhenhua , Miao Jinfeng
Published: March 2021

Streptococcus uberis infection can cause serious inflammation and damage to mammary epithelial cells and tissues that can be significantly alleviated by taurine. Autophagy plays an important role in regulating immunity and clearing invasive pathogens and may be regulated by taurine. However, the relationships between taurine, autophagy, and S. uberis infection remain unclear. Herein, we demonstrate that taurine augments PTEN activity and inhibits Akt/mTOR signaling, which decreases phosphorylation of ULK1 and ATG13 by mTOR and activates autophagy. Activating autophagy accelerates the degradation of intracellular S. uberis, reduces intracellular bacterial load, inhibits over-activation of the NF-κB pathway, and alleviates the inflammation and damage caused by S. uberis infection. This study increases our understanding of the mechanism through which taurine regulates autophagy and is the first to demonstrate the role of autophagy in S. uberis infected MAC-T cells. Our study also provides a theoretical basis for employing nutritional elements (taurine) to regulate innate immunity and control S. uberis infection. It also provides theoretical support for the development of prophylactic strategies for this important pathogen.
Necroptosis Underlies Hepatic Damage in a Piglet Model of Lipopolysaccharide-Induced Sepsis
Authors: Xu Qiao , Guo Junjie , Li Xiangen , Wang Yang , Wang Dan , Xiao Kan , Zhu Huiling , Wang Xiuying , Hu Chien-An Andy , Zhang Guolong , Liu Yulan
Published: March 2021

Background

Necroptosis is a newly recognized form of programmed cell death with characteristics of both necrosis and apoptosis. The role of necroptosis in hepatic damage during sepsis is poorly understood. In this study, we investigated the occurrence of necroptosis in hepatic damage, and its contribution to hepatic damage in a piglet model of lipopolysaccharide (LPS)-induced sepsis.

Methods

Two animal experiments were conducted. In trial 1, piglets were challenged with LPS and sacrificed at different time points after LPS challenge. In trial 2, piglets were pretreated with necrostatin-1, a specific inhibitor of necroptosis, prior to LPS challenge. Alterations in the hepatic structure and function, pro-inflammatory cytokine expression, and the necroptosis signaling pathway were investigated. Typical ultrastructural characteristics of cell necrosis was observed in the liver of LPS-challenged piglets.

Results

Expressions of critical components of necroptosis including kinases (RIP1, RIP3, and MLKL), mitochondrial proteins (PGAM5 and DRP1), and an intracellular damage-associated molecular pattern (HMGB1) were increased in the liver in a time-dependent manner, followed by hepatic inflammation, morphological damage, and dysfunction as manifested by elevated hepatic expression of IL-1β, IL-6 and TNF-α as well as increased serum AST and AKP activities and the AST/ALT ratio. Pretreatment with necrostatin-1 significantly reduced the expression of RIP1, RIP3 and MLKL as well as PGAM5, DRP1 and HMGB1, which subsequently led to obvious attenuation of hepatic inflammation and damage.

Conclusions

Our study demonstrates that necroptosis occurs in the liver during sepsis and contributes to septic hepatic injury.
Autoimmune and Rheumatic Manifestations Associated With COVID-19 in Adults: An Updated Systematic Review
Authors: Tang Kuo-Tung , Hsu Bo-Chueh , Chen Der-Yuan
Published: March 2021

Background:Numerous cases of the coronavirus disease 2019 (COVID-19) with autoimmune and rheumatic manifestations have been reported. Despite the available reviews that summarized its autoimmune/rheumatic manifestations, a systematic approach is still lacking. Therefore, we conducted a comprehensive systematic review in order to give an overview upon these rare but clinically significant manifestations.

Methods:We performed a literature search of PubMed and EMBASE as of October 9, 2020. All articles relevant to either systemic or organ-specific autoimmune and rheumatic manifestations potentially associated with COVID-19 were collected. The reviewed literature were limited to adults ≥18 years.

Results:Although most of the existing evidence was based on case reports or case series without a long-term follow-up, a variety of autoimmune/rheumatic manifestations were associated with COVID-19. The manifestations that have a consistent association with COVID-19 include autoimmune cytopenia, cutaneous vasculitis, encephalitis, and Guillain-Barre syndrome. Such association is conflicting as regards to antiphospholipid syndrome, hemophagocytic lymphohistiocytosis, and myasthenia gravis.

Conclusion:Our systematic review indicated the potential of the COVID-19 virus to trigger a myriad of autoimmune and rheumatic manifestations, which should be considered amid global efforts to combat COVID-19.
Autologous Stem Cell Transplantation for Myeloma: Cytoreduction or an Immunotherapy?
Authors: Minnie Simone A. , Hill Geoffrey R.
Published: March 2021

The incidence of multiple myeloma (MM), a bone marrow (BM) resident hematological malignancy, is increasing globally. The disease has substantial morbidity and mortality and remains largely incurable. Clinical studies show that autologous stem cell transplantation (ASCT) remains efficacious in eligible patients, providing a progression free survival (PFS) benefit beyond novel therapies alone. Conventionally, improved PFS after ASCT is attributed to cytoreduction from myeloablative chemotherapy. However, ASCT results in immune effects beyond cytoreduction, including inflammation, lymphodepletion, T cell priming via immunogenic cell death, and disruption of the tumor BM microenvironment. In fact, a small subset of patients achieve very long-term control of disease post-ASCT, akin to that seen in the context of immune-mediated graft-vs.-myeloma effects after allogeneic SCT. These clinical observations coupled with recent definitive studies in mice demonstrating that progression after ASCT represents immune escape as a consequence of T cell exhaustion, highlight the potential for new immunotherapy maintenance strategies to prevent myeloma progression following consolidation with ASCT.
Submesoscale Mixing Across the Mixed Layer in the Gulf of Mexico
Authors: Liu Guangpeng , Bracco Annalisa , Sitar Alexandra
Published: March 2021

Submesoscale circulations influence momentum, buoyancy and transport of biological tracers and pollutants within the upper turbulent layer. How much and how far into the water column this influence extends remain open questions in most of the global ocean. This work evaluates the behavior of neutrally buoyant particles advected in simulations of the northern Gulf of Mexico by analyzing the trajectories of Lagrangian particles released multiple times at the ocean surface and below the mixed layer. The relative role of meso- and submesoscale dynamics is quantified by comparing results in submesoscale permitting and mesoscale resolving simulations. Submesoscale circulations are responsible for greater vertical transport across fixed depth ranges and also across the mixed layer, both into it and away from it, in all seasons. The significance of the submesoscale-induced transport, however, is far greater in winter. In this season, a kernel density estimation and a detailed vertical mixing analysis are performed. It is found that in the large mesoscale Loop Current eddy, upwelling into the mixed layer is the major contributor to the vertical fluxes, despite its clockwise circulation. This is opposite to the behavior simulated in the mesoscale resolving case. In the “submesoscale soup,” away from the large mesoscale structures such as the Loop Current and its detached eddies, upwelling into the mixed layer is distributed more uniformly than downwelling motions from the surface across the base of the mixed layer. Maps of vertical diffusivity indicate that there is an order of magnitude difference among simulations. In the submesoscale permitting case values are distributed around 10–3 m2 s–1 in the upper water column in winter, in agreement with recent indirect estimates off the Chilean coast. Diffusivities are greater in the eastern portion of the Gulf, where the submesoscale circulations are more intense due to sustained density gradients supplied by the warmer and saltier Loop Current.
Biosilicate® Glass-Ceramic Foams From Refined Alkali Activation and Gel Casting
Authors: Bernardo Enrico , Elsayed Hamada , Romero Acacio Rincon , Crovace Murilo C. , Zanotto Edgar D. , Fey Tobias
Published: March 2021

Biosilicate® glass-ceramics are among the most valid alternatives to 45S5 Bioglass. They combine a similar bioactivity and bioresorbability as the 45S5 with superior mechanical strength, owing to the crystallization of a Na–Ca silicate phase. This crystallization may be experienced upon viscous flow sintering of fine glass powders, thus configuring a sinter-crystallization process. As crystallization is seldom complete, sintering can also be applied to semicrystalline powders. The sintering/crystallization combination may be exploited for shaping highly porous bodies, to be used as scaffolds for bone tissue engineering, in the form of foams. The present study aims at exploring a gel-casting process, based on the room temperature foaming of powders suspended in a “weakly alkaline” (1 M NaOH) aqueous solution, followed by sintering at 1,000°C. The gelation of suspensions is attributed to the formation of hydrated compounds, later decomposed upon firing. Amorphous powders provided more intense gelation than semicrystalline ones, promoted a more homogeneous foaming, and stimulated a substantial crystallization upon firing. The homogeneity of foamed samples was assessed using micro-tomography and was further improved by casting foamed suspensions (“foam casting”) before setting.
Multi-Physics of Dynamic Elastic Metamaterials and Earthquake Systems
Authors: Yakovleva A. A. , Movchan I. B. , Misseroni D. , Pugno N. M. , Movchan A. B.
Published: March 2021

Microstructured materials, namely metamaterials, are one of the most relevant topics of the recent period due to their interdisciplinary nature. Driven by their wide range of applications, we provide an overview of a class of elastic solids which embed dynamic microstructures capable of trapping energy when subject to dynamic loads. Based on the recently developed modeling approaches, we show several applications related to wave cloaking, filtering and also multi-structured surfaces, often referred to as meta-surfaces. These culminate in the analysis of a practical example, based on a real-life recent seismic event induced by a hydrofracture exploration. The latter shows the viability of the vibration analysis in the assessment of the seismic response, and also the role of meta-surfaces as localisers of vibrations, e.g. suggesting non-periodic earthquake tolerant design strategies of housing estates.
Case Report: A Severe SARS-CoV-2 Infection in a Teenager With Angelman Syndrome
Authors: Lopes Alessandra G. D. , Celestino Camila S. H. , Barros Tiago T. A. , Fevereiro Aline G. , Gejer Debora H. , Oliveira Fernando M. F. , Brasil Jamile M. , Bossolan Rosely M. , Pinto Gabriela C. C. , Santos Ana C. E. Z. , Divan Luis A. , Alves Ingrid A. B. , Oliveira Danielle B. L. , Machado Rafael R. G. , Thomazelli Luciano M. , Hiyane Meire I. , Brelaz-Abreu Leonília , Bragança-Jardim Elayne , Heinen Letícia B. S. , Barrientos Anna C. M. , Mau Luciana B. , Camara Niels O. S. , Bueno Daniela F. , Amano Mariane T.
Published: March 2021

Teenagers generally present mild to no symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the present report, we present the case of a 14-year-old boy with Angelman syndrome (AS) who presented with severe COVID-19 symptoms. He spent 20 days in the ICU with elevated inflammatory biomarkers (C-reactive protein and D-dimer) and increased peaks of neutrophil-to-lymphocyte ratio, which is uncommon for teenagers diagnosed with COVID-19. Although he showed physiological instability, he was able to produce neutralizing antibodies, suggesting a functional immune response. The literature concerning the immune response to infections in patients with AS is still poor, and to our knowledge, this was the first report of a patient with AS diagnosed with COVID-19. As such, the present study may alert other patients with AS or other rare diseases that they lack a competent immune response and could suffer severe consequences of SARS-CoV-2 infection.
Case Report: Kidney Transplantation in a Patient With Acquired Agammaglobulinemia and SLE. Issues and Challenges
Authors: Pavlakou Paraskevi , Papasotiriou Marios , Ntrinias Theodoros , Kourakli Alexandra , Bratsiakou Adamantia , Goumenos Dimitrios S. , Papachristou Evangelos
Published: March 2021

Lupus nephritis in the context of Systemic Lupus Erythematosus (SLE) is characterized by an unpredicted course with remissions and flare-ups. Among others, it remains a significant cause of end-stage kidney disease (ESKD) in relatively young patients. Therapeutic regimens with newer immunosuppressive agents have been introduced in order to control SLE clinical manifestations more efficiently and limit organ damage induced by immune complex formation and sustained inflammation. Treatment is usually long-term, and the cumulative impact of immunosuppression is expressed through the increased frequency of infections and neoplasms. However, if the observed immunity dysregulation is secondary and pharmaceutically induced or there is a pre-existing, primary immunodeficiency that shares common pathogenetic pathways with SLE's autoimmunity is not always clear. Herein, we present the case of a 39-year-old woman, that reached ESKD due to lupus nephritis. After an upper respiratory cytomegalovirus (CMV) infection and concomitant CMV reactivations the investigation revealed significant immunodeficiency. Not long after the initiation of intravenous immunoglobulin (IVIG) administration, patient received a cadaveric kidney transplant. IVIG was continued along with standard immunosuppression so that both recurrent infections and allograft rejection are avoided. Patient is closely monitored, and her post-transplant course is remarkably satisfying so far. ESKD patients with immunodeficiency syndromes should not be excluded by definition from kidney transplantation.
Isolation of the ZmERS4 Gene From Maize and Its Functional Analysis in Transgenic Plants
Authors: Hang Tianlu , Ling Xuezhi , He Cheng , Xie Shanshan , Jiang Haiyang , Ding Ting
Published: March 2021

A gene encoding a protein similar to ethylene receptor was isolated from maize (Zea mays L.), which was named as ZmERS4.The gene was 1,905 bp in length with an open reading frame that encoded a protein consisting of 634 amino acids. The homologous analysis showed that ZmERS4 shared high similarity with the ethylene receptor protein, OsERS1, from rice (Oryza sativa L.). ZmERS4 grouped into the ETR1 subfamily of ethylene receptors based on its conserved domain and phylogenetic status. Tissue-specific and induced expression analyses indicated that ZmERS4 was differentially expressed in maize tissues, predominantly in the stems and leaves, and was induced by salicylic acid (SA). Overexpression of ZmERS4 in Arabidopsis improved resistance against the bacterial pathogen, PstDC3000, by inducing the expression of SA signaling-related genes. Moreover, treatment with flg22 induced the expression of the defense-related gene, PR1, in maize protoplasts that transiently expressed ZmERS4. Furthermore, the ultra-high-performance liquid chromatography (UPLC) analysis showed that the SA contents in ZmERS4-overexpressing Arabidopsis lines were significantly higher than the control lines. Additionally, the improved resistance of ZmERS4-overexpressing Arabidopsis against PstDC3000 was blocked after pretreatment with the SA biosynthetic inhibitor, ABT. Based on the collective findings, we hypothesize that ZmERS4 plays an important role in disease resistance through SA-mediated signaling pathways.
High-Level Extracellular Expression of a New β-N-Acetylglucosaminidase in Escherichia coli for Producing GlcNAc
Authors: Li Congna , Jiang Shun , Du Chao , Lu Zhenghui , He Nisha , Zhou Yuling , Jiang S Sijing , Zhang G Guimin
Published: March 2021

N-acetyl-β-D glucosamine (GlcNAc) is wildly used in cosmetics, nutraceuticals and pharmaceuticals. The traditional chemical process for GlcNAc production from chitin causes serious acidic pollution. Therefore, the enzymatic hydrolysis becomes a great promising and alternative strategy to produce GlcNAc. β-N-acetylglucosaminidase (NAGase) can hydrolyze chitin to produce GlcNAc. Here, a GH3 family NAGase encoding gene BlNagZ from Bacillus licheniformis was expressed extracellularly in Escherichia coli guided by signal peptide PelB. The recombinant BlNagZ presented the best activity at 60°C and pH 5.5 with a high specific activity of 13.05 U/mg. The BlNagZ activity in the fermentation supernatant can reach 13.62 U/mL after optimizing the culture conditions, which is 4.25 times higher than optimization before. Finally, combining BlNagZ with chitinase ChiA we identified before, chitin conversion efficiency to GlcNAc can reach 89.2% within 3.5 h. In all, this study provided not only a high active NAGase, and a secreted expression strategy to reduce the cost of production, which is conducive to the industrial application.
A Large-Scale Sequencing-Based Survey of Plasmids in Listeria monocytogenes Reveals Global Dissemination of Plasmids
Authors: Schmitz-Esser Stephan , Anast Justin M. , Cortes Bienvenido W.
Published: March 2021

The food-borne pathogen Listeria monocytogenes is known for its capacity to cope with multiple stress conditions occurring in food and food production environments (FPEs). Plasmids can provide benefits to their host strains, and it is known that various Listeria strains contain plasmids. However, the current understanding of plasmid frequency and function in L. monocytogenes strains remains rather limited. To determine the presence of plasmids among L. monocytogenes strains and their potential contribution to stress survival, a comprehensive dataset was established based on 1,921 published genomes from strains representing 14 L. monocytogenes sequence types (STs). Our results show that an average of 54% of all L. monocytogenes strains in the dataset contained a putative plasmid. The presence of plasmids was highly variable between different STs. While some STs, such as ST1, ST2, and ST4, contained few plasmid-bearing strains (<15% of the strains per ST), other STs, such as ST121, ST5, ST8, ST3, and ST204, possessed a higher proportion of plasmid-bearing strains with plasmids found in >71% of the strains within each ST. Overall, the sizes of plasmids analyzed in this study ranged from 4 to 170 kbp with a median plasmid size of 61 kbp. We also identified two novel groups of putative Listeria plasmids based on the amino acid sequences of the plasmid replication protein, RepA. We show that highly conserved plasmids are shared among Listeria strains which have been isolated from around the world over the last few decades. To investigate the potential roles of plasmids, nine genes related to stress-response were selected for an assessment of their abundance and conservation among L. monocytogenes plasmids. The results demonstrated that these plasmid genes exhibited high sequence conservation but that their presence in plasmids was highly variable. Additionally, we identified a novel transposon, Tn7075, predicted to be involved in mercury-resistance. Here, we provide the largest plasmid survey of L. monocytogenes to date with a comprehensive examination of the distribution of plasmids among L. monocytogenes strains. Our results significantly increase our knowledge about the distribution, composition, and conservation of L. monocytogenes plasmids and suggest that plasmids are likely important for the survival of L. monocytogenes in food and FPEs.
Plant Cell Wall as a Key Player During Resistant and Susceptible Plant-Virus Interactions
Authors: Kozieł Edmund , Otulak-Kozieł Katarzyna , Bujarski Józef Julian
Published: March 2021

The cell wall is a complex and integral part of the plant cell. As a structural element it sustains the shape of the cell and mediates contact among internal and external factors. We have been aware of its involvement in both abiotic (like drought or frost) and biotic stresses (like bacteria or fungi) for some time. In contrast to bacterial and fungal pathogens, viruses are not mechanical destructors of host cell walls, but relatively little is known about remodeling of the plant cell wall in response to viral biotic stress. New research results indicate that the cell wall represents a crucial active component during the plant’s response to different viral infections. Apparently, cell wall genes and proteins play key roles during interaction, having a direct influence on the rebuilding of the cell wall architecture. The plant cell wall is involved in both susceptibility as well as resistance reactions. In this review we summarize important progress made in research on plant virus impact on cell wall remodeling. Analyses of essential defensive wall associated proteins in susceptible and resistant responses demonstrate that the components of cell wall metabolism can affect the spread of the virus as well as activate the apoplast- and symplast-based defense mechanisms, thus contributing to the complex network of the plant immune system. Although the cell wall reorganization during the plant-virus interaction remains a challenging task, the use of novel tools and methods to investigate its composition and structure will greatly contribute to our knowledge in the field.
Comprehensive Analysis of Ferroptosis Regulators in Lung Adenocarcinomas Identifies Prognostic and Immunotherapy-Related Biomarkers
Authors: Sun Sijin , Guo Wei , Lv Fang , Zhang Guochao , Wang Juhong , Li Renda , Tan Fengwei , Li Ning , Xue Qi , Gao Yibo , Gao Shugeng , He Jie
Published: March 2021

Ferroptosis is a newly discovered type of programmed cell death that differs from canonical apoptosis. However, the potential role of ferroptosis in lung adenocarcinoma (LUAD) has not been elaborated. In total, 1,328 samples from databases and 36 ferroptosis regulators were included in this study. By combining random survival forest and principal component analysis algorithms, a robust prognostic ferroptosis-related risk score (FRRS) was constructed, and the performance was validated in three independent datasets. Based on the median risk score, two subgroups were identified. Then, comparisons, including of mutational profiles, functional enrichment analyses and immune components, were conducted between subgroups. An immunotherapy cohort was applied to explore potential therapeutic-related biomarkers. Finally, the clinical utility of FRRS was validated in a proteomic cohort. In the TCGA-LUAD cohort, FRRS was calculated using the expression of 11 selected genes, and patients with high FRRS had a significantly (p < 0.001) worse prognosis than those with low FRRS. Multivariate regression suggested that FRRS was an independent prognostic factor. Functional enrichment analysis indicated that FRRS was mainly involved in cell cycle, metabolic and immune-related pathways. Furthermore, FRRS was shown to be significantly (p < 0.001) associated with the abundance of CD8 T cells and tumor mutation burden (TMB). The combination of TMB and FANCD2 expression, the main contributor to FRRS, substantially increased the precision of predicting the therapeutic response. In conclusion, the present study revealed the potential role of ferroptosis regulators in LUAD and identified ferroptosis-related biomarkers for prognostic and immunotherapeutic predictions.
Neurocognitive Trajectories After 72 Weeks of First-Line Anti-retroviral Therapy in Vietnamese Adults With HIV-HCV Co-infection
Authors: Paul Robert H. , Shikuma Cecilia M. , Chau Nguyen Van Vinh , Ndhlovu Lishomwa C. , Thanh Nguyen Tat , Belden Andrew C. , Chow Dominic C. , Chew Glen M. , Premeaux Thomas A. , Ly Vo Trieu , McBride Joseph A. D. , Bolzenius Jacob D. , Le Thuy
Published: March 2021

Background: Long-term neurocognitive outcomes following first-line suppressive anti-retroviral therapy (ART) remain uncertain for individuals with HIV and hepatitis C (HCV) co-infection. The study examined neurocognitive performance before and after 72 weeks of ART using repeated multivariate analyses and latent trajectory models.

Methods: One hundred and sixty adults with chronic, untreated HIV infection (n = 80 with HCV co-infection and n = 80 HIV mono-infected) and 80 demographically similar healthy controls were recruited from the Hospital for Tropical Diseases in Ho Chi Minh City and the surrounding community, respectively. Neurocognitive measures (adapted for use in Vietnam) and liver enzyme tests were compared across groups at baseline. Repeated multivariate and group-based trajectory analyses (GBTA) examined neurocognitive subgroup profiles of the co-infected individuals after 72 weeks of de novo efavirenz- (n = 41) or raltegravir-based (n = 39) ART.

Results: Baseline analyses revealed worse motor function in HIV-HCV co-infected individuals compared to both comparison groups. Longitudinal analyses revealed improved neurocognitive performance by week 48 for most participants regardless of treatment arm. GBTA identified a subgroup (35% of HIV-HCV sample) with persistent motor impairment despite otherwise successful ART. Higher HIV viral load and lower CD4+ T cell count at baseline predicted persistent motor dysfunction. Liver indices and ART regimen did not predict neurocognitive outcomes in HIV-HCV co-infected individuals.

Conclusions: Most HIV-HCV co-infected individuals achieve normative neurocognitive performance after 48 weeks of de novo suppressive ART. However, individuals with more severe HIV disease prior to ART exhibited motor impairment at baseline and 72 weeks after otherwise successful treatment. Interventions aimed at improving motor symptoms at the time of HIV treatment onset may improve long-term clinical outcomes in HIV-HCV co-infected adults.
Frequency- and Area-Specific Phase Entrainment of Intrinsic Cortical Oscillations by Repetitive Transcranial Magnetic Stimulation
Authors: Okazaki Yuka O. , Nakagawa Yumi , Mizuno Yuji , Hanakawa Takashi , Kitajo Keiichi
Published: March 2021

Synchronous oscillations are ubiquitous throughout the cortex, but the frequency of oscillations differs from area to area. To elucidate the mechanistic architectures underlying various rhythmic activities, we tested whether spontaneous neural oscillations in different local cortical areas and large-scale networks can be phase-entrained by direct perturbation with distinct frequencies of repetitive transcranial magnetic stimulation (rTMS). While recording the electroencephalogram (EEG), we applied single-pulse TMS (sp-TMS) and rTMS at 5, 11, and 23 Hz over the motor or visual cortex. We assessed local and global modulation of phase dynamics using the phase-locking factor (PLF). sp-TMS to the motor and the visual cortex triggered a transient increase in PLF in distinct frequencies that peaked at 21 and 8 Hz, respectively. rTMS at 23 Hz over the motor cortex and 11 Hz over the visual cortex induced a prominent and progressive increase in PLF that lasted for a few cycles after the termination of rTMS. Moreover, the local increase in PLF propagated to other cortical areas. These results suggest that distinct cortical areas have area-specific oscillatory frequencies, and the manipulation of oscillations in local areas impacts other areas through the large-scale oscillatory network with the corresponding frequency specificity. We speculate that rTMS that is close to area-specific frequencies (natural frequencies) enables direct manipulation of brain dynamics and is thus useful for investigating the causal roles of synchronous neural oscillations. Moreover, this technique could be used to treat clinical symptoms associated with impaired oscillations and synchrony.
High-Order Laplacian Regularized Low-Rank Representation for Multimodal Dementia Diagnosis
Authors: Dong Aimei , Li Zhigang , Wang Mingliang , Shen Dinggang , Liu Mingxia
Published: March 2021

Multimodal heterogeneous data, such as structural magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF), are effective in improving the performance of automated dementia diagnosis by providing complementary information on degenerated brain disorders, such as Alzheimer's prodromal stage, i.e., mild cognitive impairment. Effectively integrating multimodal data has remained a challenging problem, especially when these heterogeneous data are incomplete due to poor data quality and patient dropout. Besides, multimodal data usually contain noise information caused by different scanners or imaging protocols. The existing methods usually fail to well handle these heterogeneous and noisy multimodal data for automated brain dementia diagnosis. To this end, we propose a high-order Laplacian regularized low-rank representation method for dementia diagnosis using block-wise missing multimodal data. The proposed method was evaluated on 805 subjects (with incomplete MRI, PET, and CSF data) from the real Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Experimental results suggest the effectiveness of our method in three tasks of brain disease classification, compared with the state-of-the-art methods.
Viruses and Endogenous Retroviruses as Roots for Neuroinflammation and Neurodegenerative Diseases
Authors: Römer Christine
Published: March 2021

Many neurodegenerative diseases are associated with chronic inflammation in the brain and periphery giving rise to a continuous imbalance of immune processes. Next to inflammation markers, activation of transposable elements, including long intrespersed nuclear elements (LINE) elements and endogenous retroviruses (ERVs), has been identified during neurodegenerative disease progression and even correlated with the clinical severity of the disease. ERVs are remnants of viral infections in the human genome acquired during evolution. Upon activation, they produce transcripts and the phylogenetically youngest ones are still able to produce viral-like particles. In addition, ERVs can bind transcription factors and modulate immune response. Being between own and foreign, ERVs are reviewed in the context of viral infections of the central nervous system, in aging and neurodegenerative diseases. Moreover, this review tests the hypothesis that viral infection may be a trigger at the onset of neuroinflammation and that ERVs sustain the inflammatory imbalance by summarizing existing data of neurodegenerative diseases associated with viruses and/or ERVs.
Impulse Control Disorders in Parkinson’s Disease: From Bench to Bedside
Authors: Augustine Andrea , Winstanley Catharine A. , Krishnan Vaishnav
Published: March 2021

Parkinson’s disease (PD) is a neurodegenerative disorder that is characterized by symptoms that impact both motor and non-motor domains. Outside of motor impairments, PD patients are at risk for impulse control disorders (ICDs), which include excessively disabling impulsive and compulsive behaviors. ICD symptoms in PD (PD + ICD) can be broadly conceptualized as a synergistic interaction between dopamine agonist therapy and the many molecular and circuit-level changes intrinsic to PD. Aside from discontinuing dopamine agonist treatment, there remains a lack of consensus on how to best address ICD symptoms in PD. In this review, we explore recent advances in the molecular and neuroanatomical mechanisms underlying ICD symptoms in PD by summarizing a rapidly accumulating body of clinical and preclinical studies, with a special focus on the utility of rodent models in gaining new insights into the neurochemical basis of PD + ICD. We also discuss the relevance of these findings to the broader problem of impulsive and compulsive behaviors that impact a range of neuropsychiatric syndromes.
Is the Depth of Invasion a Marker for Elective Neck Dissection in Early Oral Squamous Cell Carcinoma?
Authors: Aaboubout Yassine , van der Toom Quincy M. , de Ridder Maria A. J. , De Herdt Maria J. , van der Steen Berdine , van Lanschot Cornelia G. F. , Barroso Elisa M. , Nunes Soares Maria R. , ten Hove Ivo , Mast Hetty , Smits Roeland W. H. , Sewnaik Aniel , Monserez Dominiek A. , Keereweer Stijn , Caspers Peter J. , Baatenburg de Jong Robert J. , Bakker Schut Tom C. , Puppels Gerwin J. , Hardillo José A. , Koljenović Senada
Published: March 2021

Objective

The depth of invasion (DOI) is considered an independent risk factor for occult lymph node metastasis in oral cavity squamous cell carcinoma (OCSCC). It is used to decide whether an elective neck dissection (END) is indicated in the case of a clinically negative neck for early stage carcinoma (pT1/pT2). However, there is no consensus on the cut-off value of the DOI for performing an END. The aim of this study was to determine a cut-off value for clinical decision making on END, by assessing the association of the DOI and the risk of occult lymph node metastasis in early OCSCC.

Methods

A retrospective cohort study was conducted at the Erasmus MC, University Medical Centre Rotterdam, The Netherlands. Patients surgically treated for pT1/pT2 OCSCC between 2006 and 2012 were included. For all cases, the DOI was measured according to the 8th edition of the American Joint Committee on Cancer guideline. Patient characteristics, tumor characteristics (pTN, differentiation grade, perineural invasion, and lymphovascular invasion), treatment modality (END or watchful waiting), and 5-year follow-up (local recurrence, regional recurrence, and distant metastasis) were obtained from patient files.

Results

A total of 222 patients were included, 117 pT1 and 105 pT2. Occult lymph node metastasis was found in 39 of the 166 patients who received END. Univariate logistic regression analysis showed DOI to be a significant predictor for occult lymph node metastasis (odds ratio (OR) = 1.3 per mm DOI; 95% CI: 1.1–1.5, p = 0.001). At a DOI of 4.3 mm the risk of occult lymph node metastasis was >20% (all subsites combined).

Conclusion

The DOI is a significant predictor for occult lymph node metastasis in early stage oral carcinoma. A NPV of 81% was found at a DOI cut-off value of 4 mm. Therefore, an END should be performed if the DOI is >4 mm.
The Diagnostic and Immunotherapeutic Value of CD248 in Renal Cell Carcinoma
Authors: Zhang Keying , Xu Chao , Liu Shaojie , Jiang Yao , Zhao Xiaolong , Ma Shanjin , Li Yu , Yang Fa , Wang Yan , Meng Ping , Shi Changhong , Han Donghui , Wen Weihong , Qin Weijun
Published: March 2021

Background: Renal cell carcinoma (RCC) is the most common malignancy in the urinary system. Despite substantial improvements in available treatment options, the survival outcome of advanced RCC is unsatisfactory. Identifying novel biomarkers to assist in early diagnosis and to screen patients who are sensitive to immunotherapy would be beneficial. CD248 is a promising candidate that deserves to be investigated.

Methods: The Cancer Genome Atlas (TCGA) data set and clinical specimens were adopted to analyze the expression of CD248 between normal and tumor tissues. Univariate and multivariate Cox regression analyses were employed to identify independent prognostic factors and construct a CD248-based prognostic signature. The correlation among the present signature, tumor-infiltrating immune cells (TIICs), the tumor mutation burden (TMB), and immunomodulatory molecules was evaluated. The weighted gene co-expression network analysis (WGCNA), the enrichment analysis, and the miRNA correlation analysis were performed to explore the underlying mechanism of CD248 in the progression of RCC.

Results: The overexpression of CD248 in RCC was related to a poor prognosis, and a CD248-based prognostic signature could precisely stratify patients with RCC with different survival outcomes regardless of the training or testing cohort. The present signature could reflect the immunosuppressive landscape of RCC (i.e., increased infiltration of regulatory T cells and upregulated immune checkpoints), accompanied by deteriorated clinicopathologic indexes. The TMB and immunostimulatory molecules expression also increased with the risk score generated from the present signature. CD248 co-expressed gene sets were identified through the WGCNA algorithm, and several immunosuppressive Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched. The result of CD248-correlated miRNA further emphasized the importance of CD248 in RCC.

Conclusion: CD248 is a valuable biomarker to improve the diagnostic and therapeutic efficiency of RCC. The immunosuppressive effect of CD248 co-expressed genes may provide insight for the present study, and miRNA would help to reveal the mechanism of the expressive regulation of CD248.
From Victim to Minister's Advisor: A Personnal View of Child Protection in France
Authors: Greco Céline
Published: March 2021

In France, maltreatment of children, that mean “physical, sexual or emotional maltreatment, or neglect of a child” is a very underestimated phenomenon, yet it is running rampant. The various causes of child abuse are subject to denial, and the ensuing delay of identification of victims is profoundly damaging. As a medical doctor and survivor of child abuse, I have a clear vision of the shortcomings of our child protection system. Non-recognition or late recognition of cases of child abuse is directly related to a lack of knowledge and training on this subject, which leads to weaknesses both in terms of detection and reporting of potential cases. Once the children are identified, they need to receive proper care that should not be limited to the social aspects. Indeed, the victims of abuse suffer from important repercussions on their physical and mental health. Without proper care, their health as adults will be severely impacted. These children require specific care and an adapted health care pack, as well as inclusion in the child protection framework. The task force “Child health in child protection” that I manage has suggested the creation of a standardized healthcare protocol for child victims of abuse, with psychological and medical costs fully covered by the Government, especially regarding clinical psychologists and psycho-motor therapists.
Multi-Target Approaches in Metabolic Syndrome
Authors: Lillich Felix F. , Imig John D. , Proschak Ewgenij
Published: March 2021

Metabolic syndrome (MetS) is a highly prevalent disease cluster worldwide. It requires polypharmacological treatment of the single conditions including type II diabetes, hypertension, and dyslipidemia, as well as the associated comorbidities. The complex treatment regimens with various drugs lead to drug-drug interactions and inadequate patient adherence, resulting in poor management of the disease. Multi-target approaches aim at reducing the polypharmacology and improving the efficacy. This review summarizes the medicinal chemistry efforts to develop multi-target ligands for MetS. Different combinations of pharmacological targets in context of in vivo efficacy and future perspective for multi-target drugs in MetS are discussed.