bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative Analyses of mRNA Expression Profile Reveal SOCS2 and CISH Play Important Roles in GHR Mutation-Induced Excessive Abdominal Fat Deposition in the Sex-Linked Dwarf Chicken
Authors: Chen Genghua , Chen Jiahui , Wu Jingwen , Ren Xueyi , Li Limin , Lu Shiyi , Cheng Tian , Tan Liangtian , Liu Manqing , Luo Qingbin , Liang Shaodong , Nie Qinghua , Zhang Xiquan , Luo Wen
Published: January 2021

Sex-linked dwarf (SLD) chicken, which is caused by a recessive mutation of the growth hormone receptor (GHR), has been widely used in the Chinese broiler industry. However, it has been found that the SLD chicken has more abdominal fat deposition than normal chicken. Excessive fat deposition not only reduced the carcass quality of the broilers but also reduced the immunity of broilers to diseases. To find out the key genes and the precise regulatory pathways that were involved in the GHR mutation-induced excessive fat deposition, we used high-fat diet (HFD) and normal diet to feed the SLD chicken and normal chicken and analyzed the differentially expressed genes (DEGs) among the four groups. Results showed that the SLD chicken had more abdominal fat deposition and larger adipocytes size than normal chicken and HFD can promote abdominal fat deposition and induce adipocyte hypertrophy. RNA sequencing results of the livers and abdominal fats from the above chickens revealed that many DEGs between the SLD and normal chickens were enriched in fat metabolic pathways, such as peroxisome proliferator-activated receptor (PPAR) signaling, extracellular matrix (ECM)-receptor pathway, and fatty acid metabolism. Importantly, by constructing and analyzing the GHR-downstream regulatory network, we found that suppressor of cytokine signaling 2 (SOCS2) and cytokine-inducible SH2-containing protein (CISH) may involve in the GHR mutation-induced abdominal fat deposition in chicken. The ectopic expression of SOCS2 and CISH in liver-related cell line leghorn strain M chicken hepatoma (LMH) cell and immortalized chicken preadipocytes (ICP) revealed that these two genes can regulate fatty acid metabolism, adipocyte differentiation, and lipid droplet accumulation. Notably, overexpression of SOCS2 and CISH can rescue the hyperactive lipid metabolism and excessive lipid droplet accumulation of primary liver cell and preadipocytes that were isolated from the SLD chicken. This study found some genes and pathways involved in abdominal fat deposition of the SLD chicken and reveals that SOCS2 and CISH are two key genes involved in the GHR mutation-induced excessive fat deposition of the SLD chicken.
The Skeleton of Lateral Meningocele Syndrome
Authors: Canalis Ernesto
Published: January 2021

Notch (Notch1 through 4) are transmembrane receptors that determine cell differentiation and function, and are activated following interactions with ligands of the Jagged and Delta-like families. Notch has been established as a signaling pathway that plays a critical role in the differentiation and function of cells of the osteoblast and osteoclast lineages as well as in skeletal development and bone remodeling. Pathogenic variants of Notch receptors and their ligands are associated with a variety of genetic disorders presenting with significant craniofacial and skeletal manifestations. Lateral Meningocele Syndrome (LMS) is a rare genetic disorder characterized by neurological manifestations, meningoceles, skeletal developmental abnormalities and bone loss. LMS is associated with NOTCH3 gain-of-function pathogenic variants. Experimental mouse models of LMS revealed that the bone loss is secondary to increased osteoclastogenesis due to enhanced expression of receptor activator of nuclear factor kappa B ligand by cells of the osteoblast lineage. There are no effective therapies for LMS. Antisense oligonucleotides targetingNotch3and antibodies that prevent the activation of NOTCH3 are being tested in preclinical models of the disease. In conclusion, LMS is a serious genetic disorder associated with NOTCH3 pathogenic variants. Novel experimental models have offered insight on mechanisms responsible and ways to correct the disease.
Functional Characterization of Rare Genetic Variants in the N-Terminus of Complement Factor H in aHUS, C3G, and AMD
Authors: Wong Edwin K. S. , Hallam Thomas M. , Brocklebank Vicky , Walsh Patrick R. , Smith-Jackson Kate , Shuttleworth Victoria G. , Cox Thomas E. , Anderson Holly E. , Barlow Paul Nigel , Marchbank Kevin James , Harris Claire L. , Kavanagh David
Published: January 2021

Membranoproliferative glomerulonephritis (MPGN), C3 glomerulopathy (C3G), atypical haemolytic uraemic syndrome (aHUS) and age-related macular degeneration (AMD) have all been strongly linked with dysfunction of the alternative pathway (AP) of complement. A significant proportion of individuals with MPGN, C3G, aHUS and AMD carry rare genetic variants in the CFH gene that cause functional or quantitative deficiencies in the factor H (FH) protein, an important regulator of the AP. In silico analysis of the deleteriousness of rare genetic variants in CFH is not reliable and careful biochemical assessment remains the gold standard. Six N-terminal variants of uncertain significance in CFH were identified in patients with these diseases of the AP and selected for analysis. The variants were produced in Pichia Pastoris in the setting of FH CCPs 1–4, purified by nickel affinity chromatography and size exclusion and characterized by surface plasmon resonance and haemolytic assays as well as by cofactor assays in the fluid phase. A single variant, Q81P demonstrated a profound loss of binding to C3b with consequent loss of cofactor and decay accelerating activity. A further 2 variants, G69E and D130N, demonstrated only subtle defects which could conceivably over time lead to disease progression of more chronic AP diseases such as C3G and AMD. In the variants S159N, A161S, and M162V any functional defect was below the capacity of the experimental assays to reliably detect. This study further underlines the importance of careful biochemical assessment when assigning functional consequences to rare genetic variants that may alter clinical decisions for patients.
Recent Advances in Lupus B Cell Biology: PI3K, IFNγ, and Chromatin
Authors: Bacalao Maria A. , Satterthwaite Anne B.
Published: January 2021

In the autoimmune disease Systemic Lupus Erythematosus (SLE), autoantibodies are formed that promote inflammation and tissue damage. There has been significant interest in understanding the B cell derangements involved in SLE pathogenesis. The past few years have been particularly fruitful in three domains: the role of PI3K signaling in loss of B cell tolerance, the role of IFNγ signaling in the development of autoimmunity, and the characterization of changes in chromatin accessibility in SLE B cells. The PI3K pathway coordinates various downstream signaling molecules involved in B cell development and activation. It is governed by the phosphatases PTEN and SHIP-1. Murine models lacking either of these phosphatases in B cells develop autoimmune disease and exhibit defects in B cell tolerance. Limited studies of human SLE B cells demonstrate reduced expression of PTEN or increased signaling events downstream of PI3K in some patients. IFNγ has long been known to be elevated in both SLE patients and mouse models of lupus. New data suggests that IFNγR expression on B cells is required to develop autoreactive germinal centers (GC) and autoantibodies in murine lupus. Furthermore, IFNγ promotes increased transcription of BCL6, IL-6 and T-bet in B cells, which also promote GC and autoantibody formation. IFNγ also induces epigenetic changes in human B cells. SLE B cells demonstrate significant epigenetic reprogramming, including enhanced chromatin accessibility at transcription factor motifs involved in B cell activation and plasma cell (PC) differentiation as well as alterations in DNA methylation and histone modifications. Histone deacetylase inhibitors limit disease development in murine lupus models, at least in partviatheir ability to prevent B cell class switching and differentiation into plasma cells. This review will discuss relevant discoveries of the past several years pertaining to these areas of SLE B cell biology.
Strategies for Successful Research to Application Projects: A Case Study of the National Sea Grant College Program
Authors: Jones Hollis R. , Briggs Rebecca A. , Krepp Alison , Rohring Elizabeth
Published: January 2021

As coastal landscapes change, management professionals are working hard to transition research results into actions that support scientifically informed decisions impacting coastal communities. This type of research faces many challenges due to competing priorities, but boundary spanning organizations can help mediate these conflicts by forming transdisciplinary collaborations. The National Sea Grant College Program (Sea Grant), a National Oceanic and Atmospheric Administration based agency, is a networked organization of 34 university-based state programs that uses a three pronged approach of research, extension, and education to move academic research into the hands of stakeholders and decision makers. The objective of this study is to better understand strategies for successful research to application (R2A) projects that address complex environmental problems occurring in a socio-economic context. Specifically, this work examines R2A projects from the Sea Grant network to better understand the drivers for project development and common deliverables produced through the R2A process. We identify five common facilitating factors that enabled ‘successful’ R2A across all projects: platforms for partnerships, iterative communication, transparent planning, clear examples of R2A, and graduate student involvement. By providing examples of successful frameworks, we hope to encourage more organizations to engage in the R2A process.
Morphology and Molecular Phylogeny of Four Trachelocercid Ciliates (Protozoa, Ciliophora, Karyorelictea) Found in Marine Coastal Habitats of Northern China, With Description of a New Genus, Two New Species and a New Combination
Authors: Ma Mingzhen , Li Yuqing , Ma Honggang , Al-Rasheid Khaled A. S. , Warren Alan , Wang Yurui , Yan Ying
Published: January 2021

The morphology of four trachelocercid ciliates, Paratrachelocerca typica gen. nov., spec. nov., Trachelolophos monocaryon (Dragesco, 1965) comb. nov. (original combination: Tracheloraphis monocaryonDragesco, 1965), Tracheloraphis katzae spec. nov., and Tracheloraphis colubis (Kahl, 1933) Xu et al., 2011 were studied in live and protargol-stained specimens. All samples were isolated from the intertidal zone of sandy beaches at Qingdao, China. The new genus Paratrachelocerca can be distinguished from other trachelocercid genera mainly by the three circumoral kineties each composed of a row of dikinetids and the absence of a brosse or ciliary tuft in the oral cavity. The detailed investigation on the poorly described Tracheloraphis monocaryon (Dragesco, 1965) reveals that its oral infraciliature includes one uninterrupted circumoral kinety and a conspicuous ciliary tuft in the center of the oral cavity, which is consistent with the genus Trachelolophos rather than Tracheloraphis. Therefore, this species is transferred to Trachelolophos as Trachelolophos monocaryon (Dragesco, 1965) comb. nov. Tracheloraphis katzae spec. nov. can be recognized by the combination of its minute brownish cortical granules and 9–15 somatic kineties. The small subunit (SSU) rDNA of each species was sequenced for the first time. Phylogenetic analyses of the SSU rDNA show that Paratrachelocerca typica gen. nov., spec. nov. clusters with Apotrachelocerca arenicola (Kahl, 1933) Xu et al., 2011 in a group that is sister to all other trachelocercids.
In Vitro Evaluation of MgB2 Powders as Novel Tools to Fight Fungal Biodeterioration of Heritage Buildings and Objects
Authors: Gheorghe Irina , Avram Ionela , Maria Corbu Viorica , Măruţescu Luminita , Popa Marcela , Balotescu Irina , Blăjan Ion , Mateescu Venus , Zaharia Daniela , Dumbravă Andreea Ştefania , Zetu Octavia Emilia , Pecete Ionut , Cristea Violeta Corina , Batalu Dan , Grigoroscuta Mihai Alexandru , Burdusel Mihail , Aldica Gheorghe Virgil , Badica Petre , Datcu Adina Daniela , Ianovici Nicoleta , Bleotu Coralia , Lazar Veronica , Diţu Lia Mara , Chifiriuc Mariana Carmen
Published: January 2021

The 17th–19th century wooden and stone churches are an iconic symbol for the Romanian national heritage, raising urgent needs for the development of efficient and ecofriendly restoration and preservation solutions. Nanotechnology has a great but largely unexplored potential in this field, providing new tools and methods to achieve higher consolidation and protection efficiency, mainly due to the ability of nanoparticles to inhibit the growth and metabolic activity of different biodeteriorating agents, including fungi. The purpose of the present study was to report for the first time on the efficiency of MgB2materials, mainly prized for their practical superconducting properties, against a large collection of filamentous fungal strains recently isolated from biodeteriorated wooden and stone heritage objects. Four types of MgB2powders, with a crystallite size of 42–113 nm, were tested by qualitative (on 149 strains) and quantitative (on 87 strains) assays. The cytotoxicity was evaluated by the microscopic analysis of SiHa cells morphology and Hep2 cell cycle analysis and the ecotoxicity by theAlliumtest. The tested filamentous fungal strains belonged to 11 different genera, and those isolated from mural paintings and wooden objects exhibited the best capacity to colonize the inert substratum. All MgB2powders exhibited similar and relatively low minimal inhibitory concentrations (MIC) values against theAspergillusandPenicilliumisolates, which were predominated among isolates. From the tested powders, PVZ and CERAC proved to be more efficient against the strains isolated from stone and wood materials, while LTS was active against the fungal strains colonizing the mural paintings and museum objects. The cytotoxicity results indicated that the tested powders are toxic for the human cells at concentrations higher than 50 µg/ml, but, however, the very short lifetime of these NPs prevents their accumulation in the natural environment and, thus, the occurrence of toxic effects. The tested powders proved to be ecofriendly at the active antifungal concentrations, as suggested by the phytotoxicity test results. Taken together, our results suggest the potential of the MgB2materials for the development of environmentally safe antifungal substances, which can be used in the control of the material cultural heritage biodeterioration process.
Recent Advances in Non‐nucleophilic Mg Electrolytes
Authors: Wu Qijie , Shu Kewei , Sun Lili , Wang Haihua
Published: January 2021

High-performance electrolyte is still a roadblock for the development of rechargeable magnesium (Mg) batteries. Grignard-type electrolytes were once the only choice in the early stage of rechargeable Mg batteries research. However, due to their nucleophilic nature and high reactivity, Grignard-type electrolytes have inherent safety issues and low oxidation stability, which restrict the development of rechargeable Mg batteries in terms of practical application. Recently, emerging novel Mg battery systems such as Mg-S, Mg-O2/air batteries also require non‐nucleophilic electrolytes with high oxidation stability. This short review summarizes recent advances in non‐nucleophilic Mg electrolytes and aims to provide insights into electrochemical properties and active Mg ion structure of such electrolytes.
Association of Viral Infections With Oral Cavity Lesions: Role of SARS-CoV-2 Infection
Authors: La Rosa Giusy Rita Maria , Libra Massimo , De Pasquale Rocco , Ferlito Sebastiano , Pedullà Eugenio
Published: January 2021

Different viral agents, such as herpesviruses, human papillomavirus, and Coxsackie virus, are responsible for primary oral lesions, while other viruses, such as human immunodeficiency virus, affect the oral cavity due to immune system weakness. Interestingly, it has been reported that coronavirus disease 2019 (COVID-19) patients can show cutaneous manifestations, including the oral cavity. However, the association between oral injuries and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still unclear. This narrative review aimed to summarize the available literature and provide an overview of oral lesions associated with COVID-19. An online literature search was conducted to select relevant studies published up to November 2020. The results of 17 studies showed variability in oral lesions associated with COVID-19, including ulcerations, aphthous-like lesions, and macules. The tongue, lips, and palate were the most frequent anatomical locations. According to current knowledge, the etiopathogenesis of multiple COVID-19-associated lesions seems to be multifactorial. The appearance of such lesions could be related to the direct or indirect action of SARS-CoV-2 over the oral mucosa cells, coinfections, immunity impairment, and adverse drug reactions. Nevertheless, COVID-19-associated oral lesions may be underreported, mainly due to lockdown periods and the lack of mandatory dispositive protection. Consequently, further research is necessary to determine the diagnostic and pathological significance of oral manifestations of COVID-19. All medical doctors, dentists, and dermatologists are encouraged to perform an accurate and thorough oral examination of all suspected and confirmed COVID-19 cases to recognize the disease's possible early manifestations.
Characterization of Mucosal Lesions in Crohn's Disease Scored With Capsule Endoscopy: A Systematic Review
Authors: Marquès Camí Miquel , Serracarbasa Alba , D'Haens Geert , Löwenberg Mark
Published: January 2021

Background and Aims: There is little agreement on the nomenclature and description of Crohn's disease (CD) lesions that can be found in the small and large bowel using capsule endoscopy (CE). We performed a systematic review to identify mucosal lesions that have been described using CE in CD, in both the small bowel and colon, with the aim to make propositions to homogenize such descriptions.

Methods: A systematic literature search was conducted using Embase, Medline (OvidSP), and Cochrane Central on August 6, 2019. Clinical studies providing nomenclature and descriptions for small bowel and colonic inflammatory lesions using CE in CD were selected for data collection.

Results: In total, 851 articles were included for abstract screening out of which 219 were analyzed for full-text review. Twenty-two articles were selected for data extraction. Seven items, accompanied by clear descriptions, were found for the small bowel: i.e., ulcer, erosion, aphthoid lesion, edema, fissure, cobblestone appearance, and villous atrophy. No studies were found describing inflammatory items using CE in colonic CD.

Conclusions: The most frequently described CD lesions using CE were ulcers and erosions. Subjective interpretation of CE inflammatory findings plays an important role. Based on our findings, a range of suggestions regarding items and descriptions is made that might form the basis of a pan-enteric CE activity index.
Distribution of Beta-Lactamase Producing Gram-Negative Bacterial Isolates in Isabela River of Santo Domingo, Dominican Republic
Authors: Calderón Víctor V. , Bonnelly Roberto , Del Rosario Camila , Duarte Albert , Baraúna Rafael , Ramos Rommel T. , Perdomo Omar P. , Rodriguez de Francisco Luis E. , Franco Edian F.
Published: January 2021

Bacteria carrying antibiotic resistance genes (ARGs) are naturally prevalent in lotic ecosystems such as rivers. Their ability to spread in anthropogenic waters could lead to the emergence of multidrug-resistant bacteria of clinical importance. For this study, three regions of the Isabela river, an important urban river in the city of Santo Domingo, were evaluated for the presence of ARGs. The Isabela river is surrounded by communities that do not have access to proper sewage systems; furthermore, water from this river is consumed daily for many activities, including recreation and sanitation. To assess the state of antibiotic resistance dissemination in the Isabela river, nine samples were collected from these three bluedistinct sites in June 2019 and isolates obtained from these sites were selected based on resistance to beta-lactams. Physico-chemical and microbiological parameters were in accordance with the Dominican legislation. Matrix-assisted laser desorption ionization-time of flight mass spectrometry analyses of ribosomal protein composition revealed a total of 8 different genera. Most common genera were as follows: Acinetobacter (44.6%) and Escherichia (18%). Twenty clinically important bacterial isolates were identified from urban regions of the river; these belonged to genera Escherichia (n = 9), Acinetobacter (n = 8), Enterobacter (n = 2), and Klebsiella (n = 1). Clinically important multi-resistant isolates were not obtained from rural areas. Fifteen isolates were selected for genome sequencing and analysis. Most isolates were resistant to at least three different families of antibiotics. Among beta-lactamase genes encountered, we found the presence of blaTEM, blaOXA, blaSHV, and blaKPC through both deep sequencing and PCR amplification. Bacteria found from genus Klebsiella and Enterobacter demonstrated ample repertoire of antibiotic resistance genes, including resistance from a family of last resort antibiotics reserved for dire infections: carbapenems. Some of the alleles found were KPC-3, OXA-1, OXA-72, OXA-132, CTX-M-55, CTX-M-15, and TEM-1.
Quantitative Proteomic Profiling of Marine Diatom Skeletonema dohrnii in Response to Temperature and Silicate Induced Environmental Stress
Authors: Thangaraj Satheeswaran , Palanisamy Satheesh Kumar , Zhang Guicheng , Sun Jun
Published: January 2021

Global warming is expected to reduce the nutrient concentration in the upper ocean and affect the physiology of marine diatoms, but the underlying molecular mechanisms controlling these physiological changes are currently unknown. To understand these mechanisms, here we investigated iTRAQ based proteomic profiling of diatom Skeletonema dohrnii in a multifactorial experimental with a combining change of temperature and silicate concentrations. In total, 3369 differently abundant proteins were detected in four different environmental conditions, and the function of all proteins was identified using Gene Ontology and KEGG pathway analysis. For discriminating the proteome variation among samples, multivariate statistical analysis (PCA, PLS-DA) was performed by comparing the protein ratio differences. Further, performing pathway analysis on diatom proteomes, we here demonstrated downregulation of photosynthesis, carbon metabolism, and ribosome biogenesis in the cellular process that leads to decrease the oxidoreductase activity and affects the cell cycle of the diatom. Using PLS-DA VIP score plot analysis, we identified 15 protein biomarkers for discriminating studied samples. Of these, five proteins or gene (rbcL, PRK, atpB, DNA-binding, and signal transduction) identified as key biomarkers, induced by temperature and silicate stress in diatom metabolism. Our results show that proteomic finger-printing of S. dohrnii with different environmental conditions adds biological information that strengthens marine phytoplankton proteome analysis.
Effect of Two Different Sugarcane Cultivars on Rhizosphere Bacterial Communities of Sugarcane and Soybean Upon Intercropping
Authors: Liu Yue , Yang Huichun , Liu Qi , Zhao Xiaowen , Xie Sasa , Wang Ziting , Wen Ronghui , Zhang Muqing , Chen Baoshan
Published: January 2021

Intercropping of soybean and sugarcane is an important strategy to promote sustainable development of the sugarcane industry. In fact, our understanding of the interaction between the rhizosphere and bacterial communities in the intercropping system is still evolving; particularly, the influence of different sugarcane varieties on rhizosphere bacterial communities in the intercropping process with soybean, still needs further research. Here, we evaluated the response of sugarcane varieties ZZ1 and ZZ9 to the root bacterial community during intercropping with soybean. We found that when ZZ9 was intercropped with soybean, the bacterial diversity increased significantly as compared to that when ZZ1 was used. ZZ9 played a major role in changing the bacterial environment of the root system by affecting the diversity of rhizosphere bacteria, forming a rhizosphere environment more conducive to the growth of sugarcane. In addition, our study found that ZZ1 and ZZ9 had differed significantly in their utilization of nutrients. For example, nutrients were affected by different functional genes in processes such as denitrification, P-uptake and transport, inorganic P-solubilization, and organic P-mineralization. These results are significant in terms of providing guidance to the sugarcane industry, particularly for the intercropping of sugarcane and soybean in Guangxi, China.
Probiotics and MicroRNA: Their Roles in the Host–Microbe Interactions
Authors: Zhao Ying , Zeng Yan , Zeng Dong , Wang Hesong , Zhou Mengjia , Sun Ning , Xin Jinge , Khalique Abdul , Rajput Danish Sharafat , Pan Kangcheng , Shu Gang , Jing Bo , Ni Xueqin
Published: January 2021

Probiotics are widely accepted to be beneficial for the maintenance of the gut homeostasis – the dynamic and healthy interactions between host and gut microorganisms. In addition, emerging as a key molecule of inter-domain communication, microRNAs (miRNAs) can also mediate the host–microbe interactions. However, a comprehensive description and summary of the association between miRNAs and probiotics have not been reported yet. In this review, we have discussed the roles of probiotics and miRNAs in host–microbe interactions and proposed the association of probiotics with altered miRNAs in various intestinal diseases and potential molecular mechanisms underlying the action of probiotics. Furthermore, we provided a perspective of probiotics–miRNA–host/gut microbiota axis applied in search of disease management highly associated with the gut microbiome, which will potentially prove to be beneficial for future studies.
Soil Microbial Composition and phoD Gene Abundance Are Sensitive to Phosphorus Level in a Long-Term Wheat-Maize Crop System
Authors: Lang Ming , Zou Wenxin , Chen Xiuxiu , Zou Chunqin , Zhang Wei , Deng Yan , Zhu Feng , Yu Peng , Chen Xinping
Published: January 2021

Microbes associated with phosphorus (P) cycling are intrinsic to soil P transformation and availability for plant use but are also influenced by the application of P fertilizer. Nevertheless, the variability in soil P in the field means that integrative analyses of soil P cycling, microbial composition, and microbial functional genes related to P cycling remain very challenging. In the present study in the North China Plain, we subjected the bacterial and fungal communities to amplicon sequencing analysis and characterized the alkaline phosphatasegene(phoD)encoding bacterial alkaline phosphatase in a long-term field experiment (10 years) with six mineral P fertilization rates up to 200 kg P ha–1. Long-term P fertilization increased soil available P, inorganic P, and total P, while soil organic P increased until the applied P rate reached 25 kg ha–1and then decreased. The fungal alpha-diversity decreased as P rate increased, while there were no significant effects on bacterial alpha-diversity. Community compositions of bacteria and fungi were significantly affected by P rates at order and family levels. The number of keystone taxa decreased from 10 to 3 OTUs under increasing P rates from 0 to 200 kg ha–1. The gene copy numbers of the biomarker of the alkaline phosphatasephoDwas higher at moderate P rates (25 and 50 kg ha–1) than at low (0 and 12.5 kg ha–1) and high (100 and 200 kg ha–1) rates of P fertilization, and was positively correlated with soil organic P concentration. One of the keystone taxa named BacOTU3771 belonging to Xanthomonadales was positively correlated with potential functional genes encoding enzymes such as glycerophosphoryl diester phosphodiesterase, acid phosphatase and negatively correlated with guinoprotein glucose dehydrogenase. Altogether, the results show the systematic effect of P gradient fertilization on P forms, the microbial community structure, keystone taxa, and functional genes associated with P cycling and highlight the potential of moderate rates of P fertilization to maintain microbial community composition, specific taxa, and levels of functional genes to achieve and sustain soil health.
Comparative Decomposition of Humans and Pigs: Soil Biogeochemistry, Microbial Activity and Metabolomic Profiles
Authors: DeBruyn Jennifer M. , Hoeland Katharina M. , Taylor Lois S. , Stevens Jessica D. , Moats Michelle A. , Bandopadhyay Sreejata , Dearth Stephen P. , Castro Hector F. , Hewitt Kaitlin K. , Campagna Shawn R. , Dautartas Angela M. , Vidoli Giovanna M. , Mundorff Amy Z. , Steadman Dawnie W.
Published: January 2021

Vertebrate decomposition processes have important ecological implications and, in the case of human decomposition, forensic applications. Animals, especially domestic pigs (Sus scrofa), are frequently used as human analogs in forensic decomposition studies. However, recent research shows that humans and pigs do not necessarily decompose in the same manner, with differences in decomposition rates, patterns, and scavenging. The objective of our study was to extend these observations and determine if human and pig decomposition in terrestrial settings have different local impacts on soil biogeochemistry and microbial activity. In two seasonal trials (summer and winter), we simultaneously placed replicate human donors and pig carcasses on the soil surface and allowed them to decompose. In both human and pig decomposition-impacted soils, we observed elevated microbial respiration, protease activity, and ammonium, indicative of enhanced microbial ammonification and limited nitrification in soil during soft tissue decomposition. Soil respiration was comparable between summer and winter, indicating similar microbial activity; however, the magnitude of the pulse of decomposition products was greater in the summer. Using untargeted metabolomics and lipidomics approaches, we identified 38 metabolites and 54 lipids that were elevated in both human and pig decomposition-impacted soils. The most frequently detected metabolites were anthranilate, creatine, 5-hydroxyindoleacetic acid, taurine, xanthine, N-acetylglutamine, acetyllysine, and sedoheptulose 1/7-phosphate; the most frequently detected lipids were phosphatidylethanolamine and monogalactosyldiacylglycerol. Decomposition soils were also significantly enriched in metabolites belonging to amino acid metabolic pathways and the TCA cycle. Comparing humans and pigs, we noted several differences in soil biogeochemical responses. Soils under humans decreased in pH as decomposition progressed, while under pigs, soil pH increased. Additionally, under pigs we observed significantly higher ammonium and protease activities compared to humans. We identified several metabolites that were elevated in human decomposition soil compared to pig decomposition soil, including 2-oxo-4-methylthiobutanoate, sn-glycerol 3-phosphate, and tryptophan, suggesting different decomposition chemistries and timing between the two species. Together, our work shows that human and pig decomposition differ in terms of their impacts on soil biogeochemistry and microbial decomposer activities, adding to our understanding of decomposition ecology and informing the use of non-human models in forensic research.
A Carbamoyl Phosphate Synthetase II (CPSII) Deletion Mutant of Toxoplasma gondii Induces Partial Protective Immunity in Mice
Authors: Zhuo Xunhui , Du Kaige , Ding Haojie , Lou Di , Zheng Bin , Lu Shaohong
Published: January 2021

Toxoplasma gondiiis an obligate intracellular protozoan parasite.T. gondiiprimarily infection in pregnant women may result in fetal abortion, and infection in immunosuppressed population may result in toxoplasmosis. Carbamoyl phosphate synthetase II (CPSII) is a key enzyme in thede novopyrimidine-biosynthesis pathway, and has a crucial role in parasite replication. We generated a mutant with complete deletion of CPSII via clustered regularly interspaced short palindromic repeats (CRISPR)/cas9 in type-1 RH strain ofT. gondii. We tested the intracellular proliferation of this mutant and found that it showed significantly reduced replicationin vitro, though CPSII deletion did not completely stop the parasite growth. The immune responses induced by the infection of RHΔCPSII tachyzoites in mice were evaluated. During infection in mice, the RHΔCPSII mutant displayed notable defects in replication and virulence, and significantly enhanced the survival of mice compared with survival of RH-infected mice. We tracked parasite propagation from ascitic fluid in mice infected with the RHΔCPSII mutant, and few tachyzoites were observed at early infection. We also observed that the RHΔCPSII mutant induced greater accumulation of neutrophils. The mutant induced a higher level of T-helper type-1 cytokines [interferon (IFN)-γ, interleukin (IL)-12]. The mRNA levels of signal transducer and activator of transcription cellular transcription factor 1 and IFN regulatory factor 8 were significantly higher in the RHΔCPSII mutant-infected group. Together, these data suggest that CPSII is crucial for parasite growth, and that strains lack thede novopyrimidine biosynthesis pathway and salvage pathway may become a promising live attenuated vaccine to prevent infection withT. gondii.
Epithelial Infection With Candida albicans Elicits a Multi-System Response in Planarians
Authors: Maciel Eli Isael , Valle Arevalo Ashley , Ziman Benjamin , Nobile Clarissa J. , Oviedo Néstor J.
Published: January 2021

Candida albicans is one of the most common fungal pathogens of humans. Prior work introduced the planarian Schmidtea mediterranea as a new model system to study the host response to fungal infection at the organismal level. In the current study, we analyzed host–pathogen changes that occurred in situ during early infection with C. albicans. We found that the transcription factor Bcr1 and its downstream adhesin Als3 are required for C. albicans to adhere to and colonize the planarian epithelial surface, and that adherence of C. albicans triggers a multi-system host response that is mediated by the Dectin signaling pathway. This infection response is characterized by two peaks of stem cell divisions and transcriptional changes in differentiated tissues including the nervous and the excretory systems. This response bears some resemblance to a wound-like response to physical injury; however, it takes place without visible tissue damage and it engages a distinct set of progenitor cells. Overall, we identified two C. albicans proteins that mediate epithelial infection of planarians and a comprehensive host response facilitated by diverse tissues to effectively clear the infection.
Molecular Epidemiological, Serological, and Pathogenic Analysis of EV-B75 Associated With Acute Flaccid Paralysis Cases in Tibet, China
Authors: Zhang Keyi , Hong Mei , Zhang Yong , Han Zhenzhi , Xiao Jinbo , Lu Huanhuan , Song Yang , Yan Dongmei , Wang Dongyan , Zhu Shuangli , Xu Wenbo , Wu Guizhen
Published: January 2021

Enterovirus B75 (EV-B75) is a newly identified serotype of the enterovirus B species. To date, only 112 cases related to EV-B75 have been reported worldwide, and research on EV-B75 is still limited with only two full-length genome sequences available in GenBank. The present study reported seven EV-B75 sequences from a child with acute flaccid paralysis and six asymptomatic close contacts in Shigatse, Tibet. Phylogenetic analysis revealed that the Tibetan strain was possibly imported from neighboring India. Seroepidemiological analyses indicated that EV-B75 has not yet caused a large-scale epidemic in Tibet. Similarity plots and boot scanning analyses revealed frequent intertypic recombination in the non-structural region of all seven Tibet EV-B75 strains. All seven Tibetan strains were temperature-sensitive, suggesting their poor transmissibility in the environment. Overall, though the seven Tibetan strains did not cause large-scale infection, prevention and control of the novel enterovirus cannot be underestimated.
Transcriptional Riboswitches Integrate Timescales for Bacterial Gene Expression Control
Authors: Scull Catherine E. , Dandpat Shiba S. , Romero Rosa A. , Walter Nils G.
Published: January 2021

Transcriptional riboswitches involve RNA aptamers that are typically found in the 5′ untranslated regions (UTRs) of bacterial mRNAs and form alternative secondary structures upon binding to cognate ligands. Alteration of the riboswitch's secondary structure results in perturbations of an adjacent expression platform that controls transcription elongation and termination, thus turning downstream gene expression “on” or “off.” Riboswitch ligands are typically small metabolites, divalent cations, anions, signaling molecules, or other RNAs, and can be part of larger signaling cascades. The interconnectedness of ligand binding, RNA folding, RNA transcription, and gene expression empowers riboswitches to integrate cellular processes and environmental conditions across multiple timescales. For a successful response to an environmental cue that may determine a bacterium's chance of survival, a coordinated coupling of timescales from microseconds to minutes must be achieved. This review focuses on recent advances in our understanding of how riboswitches affect such critical gene expression control across time.
Binding Revisited—Avidity in Cellular Function and Signaling
Authors: Erlendsson Simon , Teilum Kaare
Published: January 2021

When characterizing biomolecular interactions, avidity, is an umbrella term used to describe the accumulated strength of multiple specific and unspecific interactions between two or more interaction partners. In contrast to the affinity, which is often sufficient to describe monovalent interactions in solution and where the binding strength can be accurately determined by considering only the relationship between the microscopic association and dissociation rates, the avidity is a phenomenological macroscopic parameter linked to several microscopic events. Avidity also covers potential effects of reduced dimensionality and/or hindered diffusion observed at or near surfaces e.g., at the cell membrane. Avidity is often used to describe the discrepancy or the “extra on top” when cellular interactions display binding that are several orders of magnitude stronger than those estimated in vitro. Here we review the principles and theoretical frameworks governing avidity in biological systems and the methods for predicting and simulating avidity. While the avidity and effects thereof are well-understood for extracellular biomolecular interactions, we present here examples of, and discuss how, avidity and the underlying kinetics influences intracellular signaling processes.
The Neuroimmunology of Guillain-Barré Syndrome and the Potential Role of an Aging Immune System
Authors: Hagen Kathleen M. , Ousman Shalina S.
Published: January 2021

Guillain-Barré syndrome (GBS) is a paralyzing autoimmune condition affecting the peripheral nervous system (PNS). Within GBS there are several variants affecting different aspects of the peripheral nerve. In general, there appears to be a role for T cells, macrophages, B cells, and complement in initiating and perpetuating attacks on gangliosides of Schwann cells and axons. Of note, GBS has an increased prevalence and severity with increasing age. In addition, there are alterations in immune cell functioning that may play a role in differences in GBS with age alongside general age-related declines in reparative processes (e.g., delayed de-differentiation of Schwann cells and decline in phagocytic ability of macrophages). The present review will explore the immune response in GBS as well as in animal models of several variants of the disorder. In addition, the potential involvement of an aging immune system in contributing to the increased prevalence and severity of GBS with age will be theorized.
Cell Adhesion Molecules Involved in Neurodevelopmental Pathways Implicated in 3p-Deletion Syndrome and Autism Spectrum Disorder
Authors: Gandawijaya Josan , Bamford Rosemary A. , Burbach J. Peter H. , Oguro-Ando Asami
Published: January 2021

Autism spectrum disorder (ASD) is characterized by impaired social interaction, language delay and repetitive or restrictive behaviors. With increasing prevalence, ASD is currently estimated to affect 0.5–2.0% of the global population. However, its etiology remains unclear due to high genetic and phenotypic heterogeneity. Copy number variations (CNVs) are implicated in several forms of syndromic ASD and have been demonstrated to contribute toward ASD development by altering gene dosage and expression. Increasing evidence points toward the p-arm of chromosome 3 (chromosome 3p) as an ASD risk locus. Deletions occurring at chromosome 3p result in 3p-deletion syndrome (Del3p), a rare genetic disorder characterized by developmental delay, intellectual disability, facial dysmorphisms and often, ASD or ASD-associated behaviors. Therefore, we hypothesize that overlapping molecular mechanisms underlie the pathogenesis of Del3p and ASD. To investigate which genes encoded in chromosome 3p could contribute toward Del3p and ASD, we performed a comprehensive literature review and collated reports investigating the phenotypes of individuals with chromosome 3p CNVs. We observe that high frequencies of CNVs occur in the 3p26.3 region, the terminal cytoband of chromosome 3p. This suggests that CNVs disrupting genes encoded within the 3p26.3 region are likely to contribute toward the neurodevelopmental phenotypes observed in individuals affected by Del3p. The 3p26.3 region contains three consecutive genes encoding closely related neuronal immunoglobulin cell adhesion molecules (IgCAMs): Close Homolog of L1 (CHL1), Contactin-6 (CNTN6), and Contactin-4 (CNTN4). CNVs disrupting these neuronal IgCAMs may contribute toward ASD phenotypes as they have been associated with key roles in neurodevelopment. CHL1, CNTN6, and CNTN4 have been observed to promote neurogenesis and neuronal survival, and regulate neuritogenesis and synaptic function. Furthermore, there is evidence that these neuronal IgCAMs possess overlapping interactomes and participate in common signaling pathways regulating axon guidance. Notably, mouse models deficient for these neuronal IgCAMs do not display strong deficits in axonal migration or behavioral phenotypes, which is in contrast to the pronounced defects in neuritogenesis and axon guidance observed in vitro. This suggests that when CHL1, CNTN6, or CNTN4 function is disrupted by CNVs, other neuronal IgCAMs may suppress behavioral phenotypes by compensating for the loss of function.
Association Between BDNF Val66Met Polymorphism and Mild Behavioral Impairment in Patients With Parkinson's Disease
Authors: Ramezani Mehrafarin , Ruskey Jennifer A. , Martens Kristina , Kibreab Mekale , Javer Zainul , Kathol Iris , Hammer Tracy , Cheetham Jenelle , Leveille Etienne , Martino Davide , Sarna Justyna R. , Gan-Or Ziv , Pfeffer Gerald , Ismail Zahinoor , Monchi Oury
Published: January 2021

Neuropsychiatric symptoms (NPS) are common in Parkinson's disease (PD) and have demonstrated an association with the p. Val66Met, a polymorphism in the BDNF gene. Mild behavioral impairment (MBI) is a validated syndrome describing emergent and persistent NPS in older adults as a marker of potential cognitive decline and dementia. This study investigated if PD patients with the Met allele were more likely to have MBI and whether they had impairments in specific domains of MBI using the Mild Behavioral Impairment Checklist (MBI-C) as the MBI ascertainment tool. One hundred forty-six PD patients were screened for neuropsychiatric and cognitive impairments with the MBI-C and the Montreal Cognitive Assessment (MoCA). All participants were genotyped for the BDNF p.Val66Met single-nucleotide polymorphism (SNP) using TaqMan Genotyping Assay. Statistical analysis was performed using multiple linear and logistic regression models. Met carriers had a 2 times higher likelihood of being MBI positive (MBI-C total score ≥8) than Val carriers. Met carriers had significantly higher MBI-C total scores and significantly greater impairments in the mood/anxiety and the psychotic domains of MBI-C compared to Val carriers. These findings indicate that the BDNF Met allele is associated with a higher neuropsychiatric burden in PD.
Drosophila parabss Flies as a Screening Model for Traditional Medicine: Anticonvulsant Effects of Annona senegalensis
Authors: Dare Samuel S. , Merlo Emiliano , Rodriguez Curt Jesus , Ekanem Peter E. , Hu Nan , Berni Jimena
Published: January 2021

Epilepsy is among the most common serious neurological disorders and affects around 50 million people worldwide, 80% of which live in developing countries. Despite the introduction of several new Anti-Epileptic Drugs (AEDs) in the last two decades, one third of treated patients have seizures refractory to pharmacotherapy. This highlights the need to develop new treatments with drugs targeting alternative seizure-induction mechanisms. Traditional medicine (TM) is used for the treatment of epilepsy in many developing countries and could constitute an affordable and accessible alternative to AEDs, but a lack of pre-clinical and clinical testing has so far prevented its wider acceptance worldwide. In this study we usedDrosophila melanogaster paralyticbangsensitive(parabss)mutants as a model for epileptic seizure screening and tested, for the first time, the anti-seizure effect of a non-commercial AED. We evaluated the effect of the African custard-apple,Annona senegalensis, which is commonly used as a TM for the treatment of epilepsy in rural Africa, and compared it with the classical AED phenytoin. Our results showed that a stem bark extract fromA. senegalensiswas significantly more effective than a leaf extract and similar to phenytoin in the prevention and control of seizure-like behavior. These results support thatDrosophilaconstitutes a robust animal model for the screening of TM with potential value for the treatment of intractable epilepsy.