bluuebunny/crossref_metadata_2025 huggingface dataset:
TRIM16 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Modulating CHIP-Mediated Degradation of RUNX2
Authors: Zhao Yi , Zhai Qiaoli , Liu Hong , Xi Xun , Chen Shuai , Liu Dongxu
Published: January 2021

Bone regeneration is the ultimate goal of periodontal therapies, in which osteogenic differentiation of human periodontal ligament stem cells plays a critical role. The tripartite motif (TRIM)16, an E3 ubiquitin ligase, is downregulated in periodontal tissues of patients with periodontitis, while the role of TRIM16 in the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) is largely unknown. Firstly, we found that TRIM16 was increased throughout the osteogenic media induced differentiation of hPDLSCs. Then overexpression plasmids and specific short-hairpin RNAs (shRNAs) were constructed to manipulate the expression of target molecules. TRIM16 significantly promoted alkaline phosphatase activity, mineralized nodule formation, and positively regulated the expression of osteo-specific markers RUNX2, COL1A1 and OCN except the mRNA of RUNX2. Mechanistically, TRIM16 serves as a pivotal factor that stabilizes RUNX2 protein levels by decreasing CHIP-mediated K48-linked ubiquitination degradation of the RUNX2 protein. This study identified a novel mechanism of TRIM16 in regulating stability of the RUNX2 protein, which promoted the osteogenic differentiation of hPDLSCs. TRIM16 may be a potential target of stem cell based-bone regeneration for periodontal therapies.
Niche-Specific Adaptive Evolution of Lactobacillus plantarum Strains Isolated From Human Feces and Paocai
Authors: Pan Qiqi , Cen Shi , Yu Leilei , Tian Fengwei , Zhao Jianxin , Zhang Hao , Chen Wei , Zhai Qixiao
Published: January 2021

Lactobacillus plantarum, a widely used probiotic in the food industry, exists in diverse habitats, which has led to its niche-specific genetic evolution. However, the relationship between this type of genetic evolution and the bacterial phenotype remains unclear. Here, six L. plantarum strains derived from paocai and human feces were analyzed at the genomic and phenotypic levels to investigate the features of adaptive evolution in different habitats. A comparative genomic analysis showed that 93 metabolism-related genes underwent structural variations (SVs) during adaptive evolution, including genes responsible for carbohydrate, lipid, amino acid, inorganic ion and coenzyme transport and metabolism, and energy production and conversion. Notably, seven virulence factor-related genes in strains from both habitats showed SVs — similar to the pattern found in the orthologous virulence genes of pathogenic bacteria shared similar niches, suggesting the possibility of horizontal gene transfer. These genomic variations further influenced the metabolic abilities of strains and their interactions with the commensal microbiota in the host intestine. Compared with the strains from feces, those from paocai exhibited a shorter stagnation period and a higher growth rate in a diluted paocai solution because of variations in functional genes. In addition, opposite correlations were identified between the relative abundances of L. plantarum strains and the genus Bifidobacterium in two media inoculated with strains from the two habitats. Overall, our findings revealed that the niche-specific genetic evolution of L. plantarum strains is associated with their fermentation abilities and physiological functions in host gut health. This knowledge can help guiding the exploration and application of probiotics from the specific niches-based probiotic exploitation.
Effects of Rhythm and Rate-Controlling Drugs in Patients With Permanent His-Bundle Pacing
Authors: Su Lan , Xia Xue , Liang Dongjie , Wu Shengjie , Xu Lei , Xu Tiancheng , Wang Songjie , Chen Xiao , Huang Weijian
Published: January 2021

Introduction: Antiarrhythmic drug therapy can affect pacemaker parameters in both the atrial and ventricular myocardium. It is not known whether antiarrhythmic drugs impact His bundle pacing/sensing parameters and His to ventricle (H-V) intervals following permanent His bundle pacing (HBP). The aims of the study were to prospectively determine the influence of rhythm and rate-controlling drugs on pacing parameters and H-V conduction after His bundle lead implantation and to assess the impact of rhythm and rate-controlling drugs on the safety of HBP.

Materials and Methods: Patients (N = 140) with QRS duration < 120 ms who met permanent pacing indications were prospectively enrolled. Propafenone, lidocaine, and adenosine were injected intravenously after implantation of 3,830 lead during the procedure. Metoprolol succinate, amiodarone, and digoxin were taken orally for 1 month. Pacing parameters before and after drug intervention was measured, including His capture threshold, sensing and impedance, H-V interval, and conduction.

Results: There were no statistically significant differences in His bundle pacing thresholds, impedance, and sensing after drug intervention at implantation or during a 2-month follow-up (P > 0.05). The HV interval was not affected except in the large-dose propafenone group where HV interval prolonged (P = 0.001). All patients maintained 1:1 H-V conduction following drug administration.

Conclusion: There was no adverse impact on the HBP parameters or H-V conduction after the administration of commonly used dosage of rhythm and rate-controlling drugs. The drugs were safe in patients with permanent His bundle pacing.
Measuring Learning in the Blink of an Eye: Adolescents' Neurophysiological Reactions Predict Long-Term Memory for Stories
Authors: Gotlieb Rebecca J. M. , Yang Xiao-Fei , Immordino-Yang Mary Helen
Published: January 2021

Anticipating what adolescents will remember is a common goal in education research, but what tools allow us to predict adolescents' memory without interrupting the learning process as it naturally occurs? To attempt to identify neurophysiological markers of deep processing that may predict long-term retention, here we conducted an exploratory study by adding a cued recall probe to the last wave of data collection in a longitudinal psychosocial and neuroimaging study of 65 urban adolescents. Five years prior, and again 3 years prior, participants had reacted to the same emotionally evocative true stories during a videotaped interview that allowed us to measure eye-blink rate (EBR), and again during fMRI scanning. We analyzed EBR and neural data from the initial story exposure. We found that memory for a story was predicted by both EBR (a proxy for striatal dopamine) and default mode network neural activity to that story (involved in integrative memory and processing of emotional feelings). EBR and default mode network activity were uncorrelated and explained additive variance. Though more work is needed, our study contributes preliminary supportive evidence linking EBR and neural activity trial-by-trial to long-term memory in a naturalistic task. The analyses suggest that including EBR, a non-invasive, portable, and inexpensive measure that can be coded from high-quality video recording, could be useful in future studies of adolescents' learning.
What Do We Mean by “Reform?”: On the Seductiveness of Reform in Teaching and Teacher Education and It's Mischievous Influences
Authors: Bullough Robert V.
Published: January 2021

Drawing on literary critic Kenneth Burke's concept of “terministic screens,” the author explores some of the history and a few of the troubling implications for the work of teachers and teacher educators that flow from the idea of reform. Concluding that “reform is a bad idea,” the author argues for an alternative conception of educational improvement, one that is more life-affirming and hopeful. Seeking to weaken the conceptual and ethical hold of reform on policy-makers and educators, the author argues with John Goodlad that educational improvement first and foremost must be understood as a learning problem, an issue of educational renewal.
Dam-Induced Hydrologic Alterations in the Rivers Feeding the Pantanal
Authors: Ely Pedro , Fantin-Cruz Ibraim , Tritico Hans M. , Girard Pierre , Kaplan David
Published: January 2021

Tropical river basins have experienced dramatically increased hydropower development over the last 20 years. These alterations have the potential to cause changes in hydrologic and ecologic systems. One heavily impacted system is the Upper Paraguay River Basin, which feeds the Pantanal wetland. The Pantanal is a Ramsar Heritage site and is one of the world's largest freshwater wetlands. Over the past 20 years, the number of hydropower facilities in the Upper Paraguay River Basin has more than doubled. This paper uses the Indicators of Hydrologic Alteration (IHA) method to assess the impact of 24 of these dams on the hydrologic regime over 20 years (10 years before and 10 years after dam installation) and proposes a method to disentangle the effects of dams from other drivers of hydrologic change using undammed “control” rivers. While most of these dams are small, run-of-the-river systems, each dam significantly altered at least one of the 33 hydrologic indicators assessed. Across all studied dams, 88 of the 256 calculated indicators changed significantly, causing changes of 5–40%, compared to undammed reaches. These changes were most common in indicators that quantify the frequency and duration of high and low pulses, along with those for the rate and frequency of hydrologic changes. Importantly, the flow regime in several undammed reaches also showed significant alterations, likely due to climate and land-use changes, supporting the need for measurements in representative control systems when attributing causes to observed change. Basin-wide hydrologic changes (in both dammed and undammed rivers) have the potential to fundamentally alter the hydrology, sediment patterns, and ecosystem of the Pantanal wetland. The proposed refinement of the IHA methods reveals crucial differences between dam-induced alteration and those assigned to other drivers of change; these need to be better understood for more efficient management of current hydropower plants or the implementation of future dams.
Distribution Patterns of Microplastics in Seawater Surface at a Portuguese Estuary and Marine Park
Authors: Rodrigues Diana , Antunes Joana , Otero Vanessa , Sobral Paula , Costa Maria Helena
Published: January 2021

Measuring local levels of marine pollution by microplastics (MP) and identifying potential sources in coastal areas is essential to evaluate the associated impacts to environment and biota. The accumulation of floating MP at the sea surface is of great concern as the neustonic habitat consists of a feeding ground for primary consumers (including filter-feeders) and active predators, which makes these organisms a relevant via of MP input into the marine trophic chain. Here, a baseline evaluation of MP accumulation at the sea surface was conducted with a neuston net (335 μm mesh) at the Arrábida coastal area, in Portugal. The study site encompasses a marine protected area and an estuary, both under strong anthropogenic pressures due to multiple activities taking place. A short-term investigation on local spatiotemporal distribution, concentration and composition of MP was performed for the first time, through the monthly collection (summer 2018 to winter 2019) of samples at 6 stations. All the neuston samples contained MP and their mean concentration was 0.45 ± 0.52 items m−3 (mean ± SD). Both the averaged MP:neuston and MP:ichthyoplankton ratios were higher in December, when concentrations of organisms decreased. Temporal distribution patterns followed expected trends, as MP concentration was clearly higher in winter months due to precipitation and runoff. Although mean MP concentrations did not vary significantly between sampling stations, there was a spatial distribution of MP in relation to particle shape and size. Fragments were the most abundant shape and MP belonging to 1–2 mm size class were dominant. Amongst a diversity of 10 polymers identified by FTIR analysis, polyethylene (PE), polypropylene (PP) and copolymer PP/PE were the most abundant. Potential links between local sources/activities and the different polymers were suggested. Altogether, the information provided in this study aims to raise awareness among the identified sectors and consequently to act toward the prevention of MP inputs in the region.
Habitat Fragmentation Increases Overall Richness, but Not of Habitat-Dependent Species
Authors: Chetcuti Jordan , Kunin William E. , Bullock James M.
Published: January 2021

Debate rages as to whether habitat fragmentation leads to the decline of biodiversity once habitat loss is accounted for. Previous studies have defined fragmentation variously, but research needs to address “fragmentation per se,” which excludes confounding effects of habitat loss. Our study controls for habitat area and employs a mechanistic multi-species simulation to explore processes that may lead some species groups to be more or less sensitive to fragmentation per se. Our multi-land-cover, landscape-scale, individual-based model incorporates the movement of generic species, each with different land cover preferences. We investigate how fragmentation per se changes diversity patterns; within (alpha), between (beta) and across (gamma) patches of a focal-land-cover, and if this differs among species groups according to their specialism and dependency on this focal-land-cover. We defined specialism as the increased competitive ability of specialists in suitable habitat and decreased ability in less suitable land covers compared to generalist species. We found fragmentation per se caused an increase in gamma diversity in the focal-land-cover if we considered all species regardless of focal-land-cover preference. However, critically for conservation, the gamma diversity of species for whom the focal land cover is suitable habitat declined under fragmentation per se. An exception to this finding occurred when these species were specialists, who were unaffected by fragmentation per se. In general, focal-land-cover species were under pressure from the influx of other species, with fragmentation per se leading to a loss of alpha diversity not compensated for by increases in beta diversity and, therefore, gamma diversity fell. The specialist species, which were more competitive, were less affected by the influx of species and therefore alpha diversity decreased less with fragmentation per se and beta diversity compensated for this loss, meaning gamma diversity did not decrease. Our findings help to inform the fragmentation per se debate, showing that effects on biodiversity can be negative or positive, depending on species’ competitive abilities and dependency on the fragmented land cover. Such differences in the effect of fragmentation per se would have important consequences for conservation. Focusing conservation efforts on reducing or preventing fragmentation in areas with species vulnerable to fragmentation.
Plant Morphoecological Traits, Grass-Weed Interactions and Water Use Efficiencies of Grasses Used for Restoration of African Rangelands
Authors: Mganga Kevin Z. , Kaindi Eric , Ndathi Aphaxard J. N. , Bosma Luwieke , Kioko Theophilus , Kadenyi Nancy , Musyoki Gilbert K. , Wambua Stephen , van Steenbergen Frank , Musimba Nashon K. R.
Published: January 2021

Degradation characterized by depleted vegetation cover is a serious environmental problem in African rangelands. It poses a serious threat to millions of pastoralists and agropastoralists who depend on livestock as a source of livelihood. Consequently, there has been a growing global interest to consolidate efforts to restore degraded ecosystems. For example, the UN decade of Ecosystem Restoration initiative aims at uniting the world behind a common goal of preventing, halting and reversing the degradation of ecosystems. Grass reseeding using native perennial species has been identified as one of the practical ecological strategies for restoring degraded African rangelands, enhancing vegetation cover and forage production. Knowledge of the multifaceted performance of African rangeland grasses in terms of morphoecological traits, interaction with weeds and water use efficiencies is however largely limited and often elusive. Perennial grasses indigenous to African rangelands Cenchrus ciliaris L. (African foxtail grass), Enteropogon macrostachyus (Hochst. Ex A. Rich.) Monro ex Benth. (Bush rye grass) and Eragrostis superba Peyr. (Maasai love grass), were established in an African semi-arid rangeland under natural conditions to fill this knowledge gap. Morphoecological plant traits: aboveground biomass (shoot, leaf and stem) production, plant densities, basal cover, tiller densities and plant height were measured 9 months after establishment. Interaction between the target grass species and weeds and water use efficiencies (WUE) were also determined. Enteropogon macrostachyus displayed significantly higher values for plant densities, tiller densities and basal cover, indices commonly used to estimate the potential of grasses for ecological restoration. Eragrostis superba produced the highest shoot biomass and water use efficiencies. This is attributed to its higher leafy biomass fraction. Higher aboveground biomass production of E. superba demonstrate its suitability for enhancing rangeland productivity. Cenchrus ciliaris suppressed the weeds. This is linked to its aggressive and allelopathic nature. In conclusion, the three perennial grasses displayed distinct morphoecological traits. In order to achieve successful seed-based restoration of degraded African rangelands using native perennial grasses, careful selection species to maximize on their unique traits is recommended. Ultimately, this selection process should match the desired restoration outcomes and subsequent use of the rangeland.
Integration of Transcriptome Resequencing and Quantitative Proteomics Analyses of Collagenase VII-Induced Intracerebral Hemorrhage in Mice
Authors: Cao Fang , Guo Yu , Zhang Qiang , Fan Yinchun , Liu Qian , Song Jiancheng , Zhong Hua , Yao Shengtao
Published: January 2021

Objective

Intracerebral hemorrhage (ICH) is a subtype of stroke with high mortality and morbidity rates. Our aim was to comprehensively analyze transcriptome and proteome in an experimental ICH model.

Methods

All mice were divided into ICH model (n = 3) and sham groups (n = 3). ICH was induced by collagenase VII. The ipsilateral hemisphere was used for whole transcriptome and proteomics resequencing. After preprocessing, differentially expressed lncRNAs (DElncRNAs), mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and DEproteins between ICH and sham groups were identified. Functional enrichment analysis was performed using the clusterProfiler package, followed by protein–protein interaction (PPI) analysis. After that, the Pearson correlation coefficient between DEmRNAs and DElncRNAs or between DEmRNAs and DEproteins was calculated. DElncRNAs with similar functions were analyzed by the GOSemSim package. After prediction of DEmiRNA–DEmRNA and DElncRNA–DEmiRNA relationships, a competing endogenous RNA (ceRNA) network was constructed. Several DEmRNAs and DElncRNAs were validated in ipsilateral hemisphere tissues of the ICH model and control groups using RT-qPCR and western blot.

Results

Between the ICH and sham groups, 31 DElncRNAs, 367 DEmRNAs, 35 DEmiRNAs, and 96 DEproteins were identified. DEmRNAs were mainly enriched in inflammation, such as cytokine–cytokine receptor interaction, IL-17, and TNF signaling pathways. A PPI network of DEmRNAs was constructed and hub genes were identified, such as IL6 (degree = 59), TNF (degree = 44), and CXCR2 (degree = 39). 24 DElncRNAs with similar functions were identified, including 15 up- and 9 down-regulated lncRNAs. After integration of DEmiRNA–DEmRNA and DElncRNA–DEmiRNA relationships, we constructed a ceRNA network, composed of 71 DEmRNAs, 17 DEmiRNAs, and 12 DElncRNAs. RT-qPCR and western blot results confirmed that C3, Fga, and Slc4a1 proteins were more lowly expressed and Penk was more highly expressed in ICH than control groups, which could become potential markers for ICH.

Conclusion

Our findings identified ICH-related DE-RNAs and proteins and potential molecular mechanisms of ICH by transcriptome resequencing and quantitative proteomic analyses.
Transcriptome Analyses Identify an RNA Binding Protein Related Prognostic Model for Clear Cell Renal Cell Carcinoma
Authors: Wu Yue , Wei Xian , Feng Huan , Hu Bintao , Liu Bo , Luan Yang , Ruan Yajun , Liu Xiaming , Liu Zhuo , Wang Shaogang , Liu Jihong , Wang Tao
Published: January 2021

RNA binding proteins (RBPs) play a key role in post-transcriptional gene regulation. They have been shown to be dysfunctional in a variety of cancers and are closely related to the occurrence and progression of cancers. However, the biological function and clinical significance of RBPs in clear cell renal carcinoma (ccRCC) are unclear. In our current study, we downloaded the transcriptome data of ccRCC patients from The Cancer Genome Atlas (TCGA) database and identified differential expression of RBPs between tumor tissue and normal kidney tissue. Then the biological function and clinical value of these RBPs were explored by using a variety of bioinformatics techniques. We identified a total of 40 differentially expressed RBPs, including 10 down-regulated RBPs and 30 up-regulated RBPs. Eight RBPs (APOBEC3G, AUH, DAZL, EIF4A1, IGF2BP3, NR0B1, RPL36A, and TRMT1) and nine RBPs (APOBEC3G, AUH, DDX47, IGF2BP3, MOV10L1, NANOS1, PIH1D3, TDRD9, and TRMT1) were identified as prognostic related to overall survival (OS) and disease-free survival (DFS), respectively, and prognostic models for OS and DFS were constructed based on these RBPs. Further analysis showed that OS and DFS were worse in high-risk group than in the low-risk group. The area under the receiver operator characteristic curve of the model for OS was 0.702 at 3 years and 0.726 at 5 years in TCGA cohort and 0.783 at 3 years and 0.795 at 5 years in E-MTAB-1980 cohort, showing good predictive performance. Both models have been shown to independently predict the prognosis of ccRCC patients. We also established a nomogram based on these prognostic RBPs for OS and performed internal validation in the TCGA cohort, showing an accurate prediction of ccRCC prognosis. Stratified analysis showed a significant correlation between the prognostic model for OS and ccRCC progression.
Interleukin 10 Restores Lipopolysaccharide-Induced Alterations in Synaptic Plasticity Probed by Repetitive Magnetic Stimulation
Authors: Lenz Maximilian , Eichler Amelie , Kruse Pia , Strehl Andreas , Rodriguez-Rozada Silvia , Goren Itamar , Yogev Nir , Frank Stefan , Waisman Ari , Deller Thomas , Jung Steffen , Maggio Nicola , Vlachos Andreas
Published: January 2021

Systemic inflammation is associated with alterations in complex brain functions such as learning and memory. However, diagnostic approaches to functionally assess and quantify inflammation-associated alterations in synaptic plasticity are not well-established. In previous work, we demonstrated that bacterial lipopolysaccharide (LPS)-induced systemic inflammation alters the ability of hippocampal neurons to express synaptic plasticity, i.e., the long-term potentiation (LTP) of excitatory neurotransmission. Here, we tested whether synaptic plasticity induced by repetitive magnetic stimulation (rMS), a non-invasive brain stimulation technique used in clinical practice, is affected by LPS-induced inflammation. Specifically, we explored brain tissue cultures to learn more about the direct effects of LPS on neural tissue, and we tested for the plasticity-restoring effects of the anti-inflammatory cytokine interleukin 10 (IL10). As shown previously, 10 Hz repetitive magnetic stimulation (rMS) of organotypic entorhino-hippocampal tissue cultures induced a robust increase in excitatory neurotransmission onto CA1 pyramidal neurons. Furthermore, LPS-treated tissue cultures did not express rMS-induced synaptic plasticity. Live-cell microscopy in tissue cultures prepared from a novel transgenic reporter mouse line [C57BL/6-Tg(TNFa-eGFP)] confirms that ex vivo LPS administration triggers microglial tumor necrosis factor alpha (TNFα) expression, which is ameliorated in the presence of IL10. Consistent with this observation, IL10 hampers the LPS-induced increase in TNFα, IL6, IL1β, and IFNγ and restores the ability of neurons to express rMS-induced synaptic plasticity in the presence of LPS. These findings establish organotypic tissue cultures as a suitable model for studying inflammation-induced alterations in synaptic plasticity, thus providing a biological basis for the diagnostic use of transcranial magnetic stimulation in the context of brain inflammation.
Seagrass Recovery Following Marine Heat Wave Influences Sediment Carbon Stocks
Authors: Aoki Lillian R. , McGlathery Karen J. , Wiberg Patricia L. , Oreska Matthew P. J. , Berger Amelie C. , Berg Peter , Orth Robert J.
Published: January 2021

Worldwide, seagrass meadows accumulate significant stocks of organic carbon (C), known as “blue” carbon, which can remain buried for decades to centuries. However, when seagrass meadows are disturbed, these C stocks may be remineralized, leading to significant CO2 emissions. Increasing ocean temperatures, and increasing frequency and severity of heat waves, threaten seagrass meadows and their sediment blue C. To date, no study has directly measured the impact of seagrass declines from high temperatures on sediment C stocks. Here, we use a long-term record of sediment C stocks from a 7-km2, restored eelgrass (Zostera marina) meadow to show that seagrass dieback following a single marine heat wave (MHW) led to significant losses of sediment C. Patterns of sediment C loss and re-accumulation lagged patterns of seagrass recovery. Sediment C losses were concentrated within the central area of the meadow, where sites experienced extreme shoot density declines of 90% during the MHW and net losses of 20% of sediment C over the following 3 years. However, this effect was not uniform; outer meadow sites showed little evidence of shoot declines during the MHW and had net increases of 60% of sediment C over the following 3 years. Overall, sites with higher seagrass recovery maintained 1.7x as much C compared to sites with lower recovery. Our study demonstrates that while seagrass blue C is vulnerable to MHWs, localization of seagrass loss can prevent meadow-wide C losses. Long-term (decadal and beyond) stability of seagrass blue C depends on seagrass resilience to short-term disturbance events.
Predicting the Effects of Climate Change on the Occurrence of the Toxic Dinoflagellate Alexandrium catenella Along Canada’s East Coast
Authors: Boivin-Rioux Aude , Starr Michel , Chassé Joël , Scarratt Michael , Perrie William , Long Zhenxia
Published: January 2021

Alexandrium catenella produces paralytic shellfish toxins that affect marine fisheries and aquaculture as well as ecosystem and human health worldwide. This harmful algal species is extremely sensitive to environmental conditions and potentially to future climate change. Using a generalized additive mixed model (GAMM) we studied the potential effects of changing salinity and temperatures on A. catenella bloom (≥1000 cells L–1) occurrence along Canada’s East Coast throughout the 21st century. Our GAMM was applied to two high greenhouse gas emissions scenarios (RCP 8.5) and one mitigation scenario (RCP 4.5). Under present-day conditions, our model successfully predicted A. catenella’s spatio-temporal distribution in Eastern Canada. Under future conditions, all scenarios predict increases in bloom frequency and spatial extent as well as changes in bloom seasonality. Under one RCP 8.5 scenario, A. catenella bloom occurrences increased at up to 3.5 days per decade throughout the 21st century, with amplified year-to-year variability. Blooms expanded into the Gulf of St. Lawrence and onto the Scotian Shelf. These conditions could trigger unprecedented bloom events in the future throughout our study region. In all climate scenarios, the bloom season intensified earlier (May–June) and ended later (October). In some areas of the Gulf of St. Lawrence, the thermal habitat of A. catenella was exceeded, thereby locally reducing bloom risk during the summer months. We conclude that an increase in A. catenella’s environmental bloom window could further threaten marine fauna including endangered species as well as fisheries and aquaculture industries on Canada’s East Coast. Similar impacts could be felt in other coastal regions of the globe where warming and freshening of waters are intensifying.
Trends in the Epidemiology of Candidemia in Intensive Care Units From 2006 to 2017: Results From the Korean National Healthcare-Associated Infections Surveillance System
Authors: Kim Eun Jin , Lee Eunyoung , Kwak Yee Gyung , Yoo Hyeon Mi , Choi Ji Youn , Kim Sung Ran , Shin Myoung Jin , Yoo So-Yeon , Cho Nan-Hyoung , Choi Young Hwa
Published: January 2021

Candidemia is an important healthcare-associated infection (HAI) in intensive care units (ICUs). However, limited research has been conducted on candidemia in the Republic of Korea. We aimed to analyze the secular trends in the incidence and distribution of candidemia in ICUs over 12-years using data from the Korean National Healthcare-Associated Infections Surveillance System (KONIS). KONIS was established in 2006 and has performed prospective surveillance of HAIs including bloodstream infections (BSIs) in ICUs. We evaluated the trends in the distribution of causative pathogens and the incidence of candidemia. From 2006 to 2017, 2,248 candidemia cases occurred in 9,184,264 patient-days (PDs). The pooled mean incidence rates of candidemia significantly decreased from 3.05 cases/10,000 PDs in 2006 to 2.5 cases/10,000 PDs in 2017 (P = 0.001). Nevertheless, the proportion of candidemia gradually increased from 15.2% in 2006 to 16.6% in 2017 (P = 0.001). The most frequent causative pathogen of BSIs from 2006 to 2012 was Staphylococcus aureus; however, Candida spp. emerged as the most frequent causative pathogen since 2013. C. albicans (39.9%) was the most common among Candida spp. causing BSIs, followed by Candida tropicalis (20.2%) and Candida parapsilosis (18.2%). The proportion of candidemia caused by C. glabrata significantly increased from 8.9% in 2006 to 17.9% in 2017 (P < 0.001). There was no significant change in the distribution of Candida spp. by year (P = 0.285). The most common source of BSIs was central lines associated BSI (92.5%). There was a significant increase in the proportion of candidemia by year in hospitals with organ transplant wards (from 18.9% in 2006 to 21.1% in 2017, P = 0.003), hospitals with <500 beds (from 2.7% in 2006 to 13.6% in 2017, P < 0.001), and surgical ICUs (from 16.2% in 2006 to 21.7% in 2017, P = 0.003). The proportion of candidemia has increased in Korea, especially in hospitals with <500 beds and surgical ICUs. Thus, appropriate infection control programs are needed.
Phosphate Dosing in Drinking Water Distribution Systems Promotes Changes in Biofilm Structure and Functional Genetic Diversity
Authors: Rosales Esther , Del Olmo Gonzalo , Calero Preciado Carolina , Douterelo Isabel
Published: January 2021

Water utilities treat drinking water by adding phosphate to prevent metal dissolution from water pipe work systems and particularly lead poisoning. Phosphate can be a limiting nutrient for microbial biofilms in DWDS, yet its effects on these microbial consortia are not well understood. This research presents results from phosphate dosing experiments using a real scale chlorinated DWDS, comparing standard phosphate concentrations of United Kingdom drinking water (1 mgP/L) with a double dose (2 mgP/L) commonly used in plumbosolvency treatment. Biofilm development during phosphate treatment experiments was monitored using a holistic approach by combining metagenomics analysis, flow cytometry and SEM characterisation. The increase of phosphate levels in drinking water, reduced biofilm cell numbers and promoted the presence of poorly distributed biofilms on inner pipe surfaces. Metagenomics analysis using genetic markers (16S rRNA and ITS2) showed that phosphate influenced biofilm community structure, particularly fungal composition. Whole metagenome sequencing showed that phosphate enrichment favoured the presence of sequencing reads associated to ATPases, ion transporters and DNA-interacting proteins, whilst reads associated to nitrogen metabolism were predominant in control samples. This research brings new knowledge regarding the influence of phosphate treatment on the composition and structure of biofilms within DWDS, and the implications that this might have for the management of these systems.
Metabolomics Analysis of the Effect of Glutamic Acid on Monacolin K Synthesis in Monascus purpureus
Authors: Zhang Chan , Zhang Nan , Chen Mengxue , Wang Haijiao , Shi Jiachen , Wang Bei , Sun Baoguo , Wang Chengtao
Published: January 2021

Monacolin K is a secondary metabolite produced by Monascus with beneficial effects on health, including the ability to lower cholesterol. We previously showed that the yield of monacolin K was significantly improved when glutamic acid was added to the fermentation broth of Monascus purpureus M1. In this study, we analyzed M. purpureus in media with and without glutamic acid supplementation using a metabolomic profiling approach to identify key metabolites and metabolic pathway differences. A total of 817 differentially expressed metabolites were identified between the two fermentation broths on day 8 of fermentation. Pathway analysis of these metabolites using the KEGG database indicated overrepresentation of the citric acid cycle; biotin metabolism; and alanine, aspartate, and glutamate metabolic pathways. Six differentially expressed metabolites were found to be related to the citric acid cycle. The effect of citric acid as an exogenous additive on the synthesis of monacolin K was examined. These results provide technical support and a theoretical basis for further studies of the metabolic regulatory mechanisms underlying the beneficial effects of monacolin K and medium optimization, as well as genetic engineering of Monascus M1 for efficient monacolin K production.
Short-Chain Dehydrogenase NcmD Is Responsible for the C-10 Oxidation of Nocamycin F in Nocamycin Biosynthesis
Authors: Mo Xuhua , Zhang Hui , Du Fengyu , Yang Song
Published: January 2021

Nocamycins I and II, featured with a tetramic acid scaffold, were isolated from the broth of Saccharothrix syringae NRRL B-16468. The biosynthesis of nocamycin I require an intermediate bearing a hydroxyl group at the C-10 position. A short chain dehydrogenase/reductase NcmD was proposed to catalyze the conversion of the hydroxyl group to ketone at the C-10 position. By using the λ-RED recombination technology, we generated the NcmD deletion mutant strain S. syringae MoS-1005, which produced a new intermediate nocamycin F with a hydroxyl group at C-10 position. We then overexpressed NcmD in Escherichia coli BL21 (DE3), purified the His6-tagged protein NcmD to homogeneity and conducted in vitro enzymatic assays. NcmD showed preference to the cofactor NAD+, and it effectively catalyzed the conversion from nocamyin F to nocamycin G, harboring a ketone group at C-10 position. However, NcmD showed no catalytic activity toward nocamyin II. NcmD achieved maximum catalytic activity at 45°C and pH 8.5. The kinetics of NcmD toward nocamycin F was investigated at 45°C, pH 8.5 in the presence of 2 mM NAD+. The Km and kcat values were 131 ± 13 μM and 65 ± 5 min−1, respectively. In this study, we have characterized NcmD as a dehydrogenase, which is involved in forming the ketone group at the C-10 position of nocamycin F. The results provide new insights to the nocamycin biosynthetic pathway.
Biomedical Evaluation of Lansium parasiticum Extract-Protected Silver Nanoparticles Against Haemonchus contortus, a Parasitic Worm
Authors: Goel Vanshita , Kaur Pawandeep , Singla Lachhman Das , Choudhury Diptiman
Published: January 2021

Here we show the novel anti-helminthic potential ofLansium parasiticumaqueous extract-protected silver nanoparticles (LAgNPs) against albendazole-resistant gastrointestinal parasiteHaemonchus contortus. LAgNPs showed LD50values of 65.6 ± 32.8 nM (12 h), 139.6 ± 39.9 nM (12 h), and 64.3 ± 8.5 nM (24 h) against adult male, female, and L3 larvae, respectively. LAgNPs was also quite effective in inhibiting egg hatching, with an IC50value of 144.4 ± 3.1 nM at 48 h of exposure. Exposure to LAgNPs generated oxidative stress and mediated physical damage in the worms' tissue. A sharp increase in reactive oxygen species and nitric oxide synthase levels was prominent due to LAgNPs' exposure. In response to oxidative stress, a sharp increase of stress-responsive enzymes' activity, like catalase, superoxide dismutase, and glutathione peroxidase activity, along with the concentration of glutathione, was observed in worm tissue, which indicated a LAgNP-responsive alteration of metabolism. The results give rise to the opportunity for the development of alternative treatment for drug-resistant parasitic worms.
The Leukotriene Receptor Antagonist Montelukast as a Potential COVID-19 Therapeutic
Authors: Aigner Ludwig , Pietrantonio Frank , Bessa de Sousa Diana Marisa , Michael Johanna , Schuster Daniela , Reitsamer Herbert Anton , Zerbe Horst , Studnicka Michael
Published: January 2021

The emergence and global impact of COVID-19 has focused the scientific and medical community on the pivotal influential role of respiratory viruses as causes of severe pneumonia, on the understanding of the underlying pathomechanisms, and on potential treatment for COVID-19. The latter concentrates onfourdifferent strategies: (i) antiviral treatments to limit the entry of the virus into the cell and its propagation, (ii) anti-inflammatory treatment to reduce the impact of COVID-19 associated inflammation and cytokine storm, (iii) treatment using cardiovascular medication to reduce COVID-19 associated thrombosis and vascular damage, and (iv) treatment to reduce the COVID-19 associated lung injury. Ideally, effective COVID-19 treatment should target as many of these mechanisms as possible arguing for the search of common denominators as potential drug targets. Leukotrienes and their receptors qualify as such targets: they are lipid mediators of inflammation and tissue damage and well-established targets in respiratory diseases like asthma. Besides their role in inflammation, they are involved in various other aspects of lung pathologies like vascular damage, thrombosis, and fibrotic response, in brain and retinal damages, and in cardiovascular disease. In consequence, leukotriene receptor antagonists might be potential candidates for COVID-19 therapeutics. This review summarizes the current knowledge on the potential involvement of leukotrienes in COVID-19, and the rational for the use of the leukotriene receptor antagonist montelukast as a COVID-19 therapeutic.
A Metabolism-Related Radiomics Signature for Predicting the Prognosis of Colorectal Cancer
Authors: Cai Du , Duan Xin , Wang Wei , Huang Ze-Ping , Zhu Qiqi , Zhong Min-Er , Lv Min-Yi , Li Cheng-Hang , Kou Wei-Bin , Wu Xiao-Jian , Gao Feng
Published: January 2021

Background: Radiomics refers to the extraction of a large amount of image information from medical images, which can provide decision support for clinicians. In this study, we developed and validated a radiomics-based nomogram to predict the prognosis of colorectal cancer (CRC).

Methods: A total of 381 patients with colorectal cancer (primary cohort: n = 242; validation cohort: n = 139) were enrolled and radiomic features were extracted from the vein phase of preoperative computed tomography (CT). The radiomics score was generated by using the least absolute shrinkage and selection operator algorithm (LASSO). A nomogram was constructed by combining the radiomics score with clinicopathological risk factors for predicting the prognosis of CRC patients. The performance of the nomogram was evaluated by the calibration curve, receiver operating characteristic (ROC) curve and C-index statistics. Functional analysis and correlation analysis were used to explore the underlying association between radiomic feature and the gene-expression patterns.

Results: Five radiomic features were selected to calculate the radiomics score by using the LASSO regression model. The Kaplan-Meier analysis showed that radiomics score was significantly associated with disease-free survival (DFS) [primary cohort: hazard ratio (HR): 5.65, 95% CI: 2.26–14.13, P < 0.001; validation cohort: HR: 8.49, 95% CI: 2.05–35.17, P < 0.001]. Multivariable analysis confirmed the independent prognostic value of radiomics score (primary cohort: HR: 5.35, 95% CI: 2.14–13.39, P < 0.001; validation cohort: HR: 5.19, 95% CI: 1.22–22.00, P = 0.026). We incorporated radiomics signature with the TNM stage to build a nomogram, which performed better than TNM stage alone. The C-index of the nomogram achieved 0.74 (0.69–0.80) in the primary cohort and 0.82 (0.77–0.87) in the validation cohort. Functional analysis and correlation analysis found that the radiomic signatures were mainly associated with metabolism related pathways.

Conclusions: The radiomics score derived from the preoperative CT image was an independent prognostic factor and could be a complement to the current staging strategies of colorectal cancer.
Identification and Analyzation of Differentially Expressed Transcription Factors in Endometriosis
Authors: Cong Shanshan , Guo Qiuyan , Cheng Yan , Gao Jianhua , Sun Liyuan , Wang Jing , Wu Han , Liang Tian , Zhang Guangmei
Published: January 2021

Background:Endometriosis is interpreted as the existence of endometrium outside the uterine cavity, such as ovaries, fallopian tubes and pelvic cavity. Dysmenorrhea, abnormal menstruation, infertility, and chronic pelvic pain are the primary symptoms of endometriosis. Although there are many theories about the origin of endometriosis, the exact factor of the disease has not been confirmed. Therefore, many other mechanisms are still worth exploring.

Materials and Methods:The gene lists of the transcription factors (TFs) were selected from the intersections of three databases. The limma R package was used to analyze the differentially expressed genes (DEGs) of GSE6364 and GSE7305 and the DEGs intersected with the TFs to obtain the differentially expressed TFs (DETFs). Subsequently, one-way ANOVA and Student'st-test were used to analyze the expression of DETFs in different phases of the endometrium and the endometrium of the infertile and fertile females with endometriosis, respectively. Enrichment analysis and PPI network were performed to reveal the molecular mechanisms of endometriosis. Finally, the plotROC R package was used to evaluate the sensitivity and specificity of hub TFs for the diagnosis of endometriosis.

Results:A total of 54 DETFs were screened out in endometriosis. The expression of up-regulated DETFs was gradually increased from the early secretory to the proliferative phase of the endometrium. Most up-regulated DETFs increased expression in the endometrium of infertile females. The pathways of DETFs were mainly enriched in stem cell differentiation, transcription activity, steroid hormone receptor activity and herpes simplex virus. Two hub TFs (RUNX2 and BATF) and two sub-networks were finally acquired from the PPI network. RUNX2 and BATF also had high diagnostic value in endometriosis.

Conclusion:We discovered and analyzed 54 DETFs that were closely related to endometriosis, which would contribute to explore new mechanisms of endometriosis and search for new diagnostic markers and effective therapeutic targets.
Brain NAD Is Associated With ATP Energy Production and Membrane Phospholipid Turnover in Humans
Authors: Cuenoud Bernard , Ipek Özlem , Shevlyakova Maya , Beaumont Maurice , Cunnane Stephen C. , Gruetter Rolf , Xin Lijing
Published: January 2021

The brain requires a large amount of energy, mostly derived from the metabolism of glucose, which decreases substantially with age and neurological diseases. While mounting evidence in model organisms illustrates the central role of brain nicotinamide adenine dinucleotide (NAD) for maintaining energy homeostasis, similar data are sparse in humans. This study explores the correlations between brain NAD, energy production and membrane phospholipid metabolism by 31-phosphorous magnetic resonance spectroscopy (31P-MRS) across 50 healthy participants including a young (mean age 27.1-year-old) and middle-aged (mean age 56.4-year-old) group. The analysis revealed that brain NAD level and NAD+/NADH redox ratio were positively associated with ATP level and the rate of energy production, respectively. Moreover, a metabolic network linking NAD with membrane phospholipid metabolism, energy production, and aging was identified. An inverted trend between age and NAD level was detected. These results pave the way for the use of 31P-MRS as a powerful non-invasive tool to support the development of new therapeutic interventions targeting NAD associated phospho-metabolic pathways in brain aging and neurological diseases.
Prefrontal Disinhibition in Social Fear: A Vital Action of Somatostatin Interneurons
Authors: Wang Jun , Tian Yuanyuan , Zeng Ling-Hui , Xu Han
Published: January 2021

Social fear and avoidance of social partners and social situations represent the core behavioral symptom of Social Anxiety Disorder (SAD), a prevalent psychiatric disorder worldwide. The pathological mechanism of SAD remains elusive and there are no specific and satisfactory therapeutic options currently available. With the development of appropriate animal models, growing studies start to unravel neuronal circuit mechanisms underlying social fear, and underscore a fundamental role of the prefrontal cortex (PFC). Prefrontal cortical functions are implemented by a finely wired microcircuit composed of excitatory principal neurons (PNs) and diverse subtypes of inhibitory interneurons (INs). Disinhibition, defined as a break in inhibition via interactions between IN subtypes that enhances the output of excitatory PNs, has recently been discovered to serve as an efficient strategy in cortical information processing. Here, we review the rodent animal models of social fear, the prefrontal IN diversity, and their circuits with a particular emphasis on a novel disinhibitory microcircuit mediated by somatostatin-expressing INs in gating social fear behavior. The INs subtype distinct and microcircuit-based mechanism advances our understanding of the etiology of social fear and sheds light on developing future treatment of neuropsychiatric disorders associated with social fear.