Effects of different emergent macrophytes on methane flux and rhizosphere microbial communities in wetlands.

Emergent macrophytes are of great importance for the structure and functioning of wetland ecosystems and play a significant role in environmental improvement, element cycling, and greenhouse gas (GHG) emissions. However, our understanding of how GHG fluxes differ among macrophyte species and its links with the microbial communities remain limited. In this study, we investigated the rhizosphere microbial communities (including total bacteria, methanotrophs, and methanogens) and the GHG fluxes associated with four emergent macrophytes-Phragmites australis, Thalia dealbata, Pontederia cordata, and Zizania latifolia-collected from Xuanwu Lake wetland, China. We observed the highest CH4 flux (FCH4) (9.35 ± 2.52 mg·m-2·h-1) from Z. latifolia zone, followed by P. australis, P. cordata, and T. dealbata zones (5.38 ± 1.63, 2.38 ± 2.91, and 2.02 ± 0.69 mg·m-2·h-1, respectively). Methanogenesis was methylotrophic at all sites, as the 13C-CH4 values were higher than -64 ‰ and the fractionation coefficients were lower than 1.055. We found a positive linear relationship between FCH4 and the methanogen community, in particular the relative abundances of Methanobacterium and Methanosarcina, indicating that the variations in FCH4 among the studied macrophyte-dominated zones might be attributed to the differences in rhizosphere microbial communities. The methane emissions in various macrophyte zones might be due to the higher capacity of methanogenesis compared to methane oxidation which was inhibited by nutrient-rich sediments. Our findings provide insights for selecting specific emergent macrophytes characterized by low FCH4 in wetland ecological restoration.

Fisetin orchestrates neuroinflammation resolution and facilitates spinal cord injury recovery through enhanced autophagy in pro-inflammatory glial cells.

BACKGROUND: Neuroinflammation, a critical component of the secondary injury cascade post-spinal cord injury, involves the activation of pro-inflammatory cells and release of inflammatory mediators. Resolution of neuroinflammation is closely linked to cellular autophagy. This study investigates the potential of Fisetin, a natural anti-inflammatory compound, to ameliorate neuroinflammation and confer spinal cord injury protection through the regulation of autophagy in pro-inflammatory cells. METHODS: Utilizing a rat T10 spinal cord injury model with distinct treatment groups (Sham, Fisetin-treated, and Fisetin combined with autophagy inhibitor), alongside in vitro models involving lipopolysaccharide (LPS)-stimulated microglial cell activation and co-culture with neurons, we employed techniques such as transcriptomic sequencing, histological assessments (immunofluorescence staining, etc.), molecular analyses (PCR, WB, ELISA, etc.), and behavioral evaluations to discern differences in neuroinflammation, autophagy, neuronal apoptosis, and neurological function recovery. RESULTS: Fisetin significantly augmented autophagic activity in injured spinal cord tissue, crucially contributing to neurological function recovery in spinal cord-injured rats. Fisetin's autophagy-dependent effects were associated with a reduction in neuronal apoptosis at the injury site. The treatment reduced the population of CD68+ and iNOS+ cells, coupled with decreased pro-inflammatory cytokines IL-6 and TNF-α levels, through autophagy-dependent pathways. Fisetin pre-treatment attenuated LPS-induced pro-inflammatory polarization of microglial cells, with this protective effect partially blocked by autophagy inhibition. Fisetin-induced autophagy in the injured spinal cord and pro-inflammatory microglial cells was associated with significant activation of AMPK and inhibition of mTOR. CONCLUSION: Fisetin orchestrates enhanced autophagy in pro-inflammatory microglial cells through the AMPK-mTOR signaling pathway, thereby mitigating neuroinflammation and reducing the apoptotic effects of neuroinflammation on neurons. This mechanistic insight significantly contributes to the protection and recovery of neurological function following spinal cord injury, underscoring the vital nature of Fisetin as a potential therapeutic agent.

Dynamics of bacterioplankton communities in the estuary areas of the Taihu Lake: Distinct ecological mechanisms of abundant and rare communities.

As the crucial confluences of rivers and lakes, the estuary areas with varied hydrodynamic exchanges intensively affect the bacterioplankton communities, whereas the ecological characteristics of the bacterioplankton in the areas have not been well understood. Here, the distribution patterns and assembly mechanisms of bacterioplankton communities in the estuary areas of the Taihu Lake were investigated using high-throughput sequencing and multivariate statistical analyses. Our results showed obvious seasonal variations in bacterioplankton diversity and community composition, which had significant correlations with water temperature. Neutral and null models together revealed that stochastic processes (especially dispersal limitation) were the major processes in shaping the communities across different seasons. By contrast, heterogeneous selection in deterministic processes exhibited increased impacts on community assembly during summer and autumn, which was significantly related to the comprehensive water quality index (WQI) rather than any single factor. In this study, rare communities displayed more pronounced seasonal dynamics compared to abundant communities, likely due to their sensitivity towards environmental factors. Accordingly, the heterogeneous selection of deterministic processes largely shaped the rare communities. These results enriched our understanding of the assembly mechanisms of bacterioplankton communities in estuary areas and emphasized the specific co-occurrence patterns of abundant and rare communities.

Epiphytic microorganisms of submerged macrophytes effectively contribute to nitrogen removal.

Submerged macrophytes play important roles in nutrient cycling and are widely used in ecological restoration to alleviate eutrophication and improve water quality in lakes. Epiphytic microbial communities on leaves of submerged macrophytes might promote nitrogen cycling, but the mechanisms and quantification of their contributions remain unclear. Here, four types of field zones with different nutrient levels and submerged macrophytes, eutrophic + Vallisneria natans (EV), eutrophic + V. natans + Hydrilla verticillata, mesotrophic + V. natans + H. verticillata, and eutrophic without macrophytes were selected to investigate the microbial communities that involved in nitrification and denitrification. The alpha diversity of bacterial community was higher in the phyllosphere than in the water, and that of H. verticillata was higher compared to V. natans. Bacterial community structures differed significantly between the four zones. The highest relative abundance of dominant bacterioplankton genera involved in nitrification and denitrification was observed in the EV zone. Similarly, the alpha diversity of the epiphytic ammonia-oxidizing archaea and nosZI-type denitrifiers were highest in the EV zone. Consist with the diversity patterns, the potential denitrification rates were higher in the phyllosphere than those in the water. Higher potential denitrification rates in the phyllosphere were also found in H. verticillata than those in V. natans. Anammox was not detected in all samples. Nutrient loads, especially nitrogen concentrations were important factors influencing potential nitrification, denitrification rates, and bacterial communities, especially for the epiphytic nosZI-type taxa. Overall, we observed that the phyllosphere harbors more microbes and promotes higher denitrification rates compared to water, and epiphytic bacterial communities are shaped by nitrogen nutrients and macrophyte species, indicating that epiphytic microorganisms of submerged macrophytes can effectively contribute to the N removal in shallow lakes.

Tofacitinib Promotes Functional Recovery after Spinal Cord Injury by Regulating Microglial Polarization via JAK/STAT Signaling Pathway.

Background: The JAK/STAT signaling pathway is the main inflammatory signal transduction pathway, whether JAK/STAT contributes the pathology of SCI and targeting the pathway will alleviate SCI needs to be addressed. Here, we explored the therapeutic effect of pan-JAK inhibitor tofacitinib (TOF) on secondary injury after SCI and explained the underlying mechanisms. Methods: SCI model in rat was established to evaluate the therapeutic effects of TOF treatment in vivo. Histological and behavioral analyses were performed at different time points after SCI. In vitro, the effects of TOF on pro-inflammatory activation of primary microglia and BV2 cells were analyzed by western blot analysis, fluorescent staining, qPCR and flow cytometry. The neuroprotection of TOF was detected using a co-culture system with primary neurons and microglia. Results: TOF can effectively improve motor dysfunction caused by spinal cord injury in rats. TOF administration in the early stage of inflammation can effectively inhibit neuronal apoptosis and scar tissue formation, and promote the repair of axons and nerve fibers. Further studies have demonstrated that TOF suppresses inflammation caused by spinal cord injury by inhibiting the activation of microglia to pro-inflammatory phenotype in vivo and in vitro. Additionally, an interesting phenomenon is revealed in our results that TOF exhibits superior neuronal protection during inflammation in vitro. Conclusions: Our study showed that TOF could regulate microglial activation via JAK / STAT pathway and promote the recovery of motor function after SCI, which is of great significance for the immunotherapy of SCI.

Top-down effects of filter-feeding fish and bivalves moderate bottom-up effects of nutrients on phytoplankton in subtropical shallow lakes: An outdoor mesocosm study.

Biomanipulation has been widely used in the ecological restoration of eutrophic lakes for decades. However, biomanipulation is prone to failure if external nutrient loads are not reduced. In order to explore the importance of filter-feeding fish and bivalves on algal control, an outdoor mesocosm experiment was conducted using different nutrient concentrations. Four treatments simulating daily loads of nutrients in Lake Taihu were studied: current, two times, and three times average daily loads of nutrients with both fish (Aristichthys nobilis) and Asian clam (Corbicula fluminea) and as a control current daily loads without fish or bivalves. Results showed that stocking of filter-feeding fish and bivalves (80 g m-3 bighead carp; 200 g cm-2 clams) at two times daily nutrient loads could effectively control water column Chl a concentrations and phytoplankton biomass. At higher nutrient concentrations (TN ≥ 260 µg L-1 d-1; TP ≥ 10 µg L-1 d-1), top-down control of filter-feeding fish and bivalves was less effective and bottom-up effects resulted in significant increases of Chl a concentration. Thus, as phytoplankton biomass in freshwater ecosystems is determined by both the top-down effects of predators and the bottom-up effects of nutrients, external loadings should be controlled when filter-feeding fish and bivalves are used for algal control to ensure the efficacy of biomanipulation.

Shift of human pathogen community composition and their potential human health risk after supply suspension in tap water.

Water supply suspension-restoration can occur frequently due to the overhauling of civil infrastructure in developing countries and the shutdown of commercial buildings during the pandemic. For comprehensive insights into the effects of water supply suspension-restoration, this study characterized the variations of the pathogen community composition of the tap water and their infection risk under different water supply scenarios. Metagenomic sequencing revealed a significant change of the human pathogen profiles, among which the most dominant pathogen changed from Pseudomonas aeruginosa (4.91%) to Acinetobacter johnsonii (0.59%). Furthermore, absolute quantification of pathogens by propidium-monoazide-qPCR revealed that the abundance of the three typical pathogens (Pseudomonas aeruginosa, Mycobacterium avium and Salmonella sp.) showed an increase of 2.44 log to 3.60 log immediately after water supply suspension-restoration and did not return to the normal level even after 2-h supply restoration, except for Pseudomonas aeruginosa. Quantitative microbial risk assessment suggested the infection risks of the three pathogens arising from direct utilization of tap water under stable water supply, including dermal exposure and oral intake, were all above the threshold of 10-4, and evidently increased after water supply suspension-restoration. This study warns us against the risk induced by the pathogens in tap water, especially after water supply suspension-restoration.

Greater transmission capacities and small-world characteristics of bacterial communities in the above- than those in the below- ground niches of a typical submerged macrophyte, Vallisneria natans.

Leaves and roots of submerged macrophytes provide extended surfaces and stable internal tissues for distinct microorganisms to rest, but how these microorganisms interact with each other across different niches and ultimately drive the distribution through horizontal and vertical transmissions remains largely undetermined. Knowledge of the mechanisms of assemblage and transmission in aquatic macrophytes-associated microbial communities will help to better understanding their important roles in plant fitness and benefit ecological functions. Here, we conducted a microcosmic experiment based on in situ lake samples to investigate the bacterial community assemblage, transmission, and co-occurrence patterns in different niches of a typical submerged macrophyte, Vallisneria natans (V. natans), including seed endosphere, as well as environmental (water and bulk sediment), epiphytic (phyllosphere and rhizosphere), and endophytic (leaf and root endosphere) microhabitats of both leaves and roots representatives of the above- and below- ground niches (AGNs and BGNs), respectively. We found the bacterial communities colonized in epiphytic niches not only exhibited the highest diversity compared to adjacent environmental and endophytic niches, but also dominated the interactions between those bacterial members of neighboring niches in both AGNs and BGNs. The host plants promoted niche specificity at bacterial community-level, as confirmed by the proportion of bacterial specialists increased with plant proximity, especially in the BGNs. Furthermore, the bacterial taxa colonized in the AGNs exhibited higher horizontal and vertical transmission capacities than those in the BGNs, especially in the vertical transmission from seeds to leaves (41.38 %) than roots (0.42 %). Meanwhile, the bacterial co-occurrence network in AGNs was shown to have stronger small-world characteristics but weaker stability than those in the BGNs. Overall, this study cast new light on the plant microbiome in the aquatic environment, thus better promoting the potential development of strategies for breeding aquatic macrophyte holobiont with enhanced water purification and pollutant removal capabilities in the future.

The association of rod curvature with postoperative outcomes in patients undergoing posterior lumbar interbody fusion for spinal stenosis: a retrospective case-control study.

BACKGROUND: Restoration of sagittal balance is a crucial consideration in posterior lumbar interbody fusion (PLIF) surgery and adverse postoperative outcomes are associated with inadequate restoration of sagittal alignment. However, there remains a shortage of substantial evidence regarding the effect of rod curvature on both sagittal spinopelvic radiographic parameters and clinical outcomes. METHOD: A retrospective case-control study was conducted in this study. Patient demographics (age, gender, height, weight and BMI), surgical characteristics (number of fused levels, surgical time, blood loss and hospital stay) and radiographic parameters (lumbar lordosis [LL], sacral slope [SS], pelvic incidence [PI], pelvic tilt [PT], PI-LL, Cobb angle of fused segments [Cobb], rod curvature [RC], Posterior tangent angle of fused segments [PTA] and RC-PTA) were analyzed. RESULTS: Patients in the abnormal group had older mean age and suffered more blood loss than those in the normal group. In addition, RC and RC-PTA were significantly lower in the abnormal group compared to the normal group. Multivariate regression analysis revealed that lower age (OR = 0.94; 95% CI: 0.89-0.99; P = 0.0187), lower PTA (OR = 0.91; 95% CI: 0.85-0.96; P = 0.0015) and higher RC (OR = 1.35; 95% CI: 1.20-1.51; P < 0.0001) were related to higher odds of better surgical outcomes. The receiver operating characteristic curve analysis showed that the ROC curve (AUC) for predicting outcomes of surgery by RC classifier was 0.851 (0.769-0.932). CONCLUSIONS: In patients who underwent PLIF surgery for lumbar spinal stenosis, those who had a satisfactory postoperative outcome tended to be younger, had lower blood loss, and higher values of RC and RC-PTA compared to those who had poor recovery and required revision surgery. Additionally, RC was found to be a reliable predictor of postoperative outcomes.

Near-infrared ratiometric fluorescent strategy for butyrylcholinesterase activity and its application in the detection of pesticide residue in food samples and biological imaging.

Butyrylcholinesterase (BChE) is an essential esterase synthesized by the liver, and its level is considered as a vital index for health evaluation. Therefore, it is of great need to develop a highly sensitive and selective tool to monitor BChE activity, which remains a considerable challenge on account of its usage in complex biological systems. A near-infrared (NIR) fluorescent probe was elaborated in this work, employing cyanine backbone to provide the intrinsic NIR fluorescence and avoid interference from bioluminescence. There presented an intriguing structural transformation upon the sensing event to shrink the conjugation in this protocol, leading to an eye-catching fluorescence change from NIR (816 nm) to red (637 nm) region, which gave rise to the proposed ratiometric assay. After an overall investigation, this receptor was verified to be applicable in a wide bio-area with ratiometric pattern, including the cellular level and slice platform. It was worth mentioning that this receptor was also discovered to be capable of monitoring pesticide dichlorvos (DDVP) residue in food samples with high sensitivity and accuracy, with significant potential to be developed as an alternative candidate for monitoring environmental pollution.

Computational Drug Discovery in Ankylosing Spondylitis-Induced Osteoporosis Based on Data Mining and Bioinformatics Analysis.

BACKGROUND: Ankylosing spondylitis (AS) and osteoporosis (OP) are both prevalent illnesses in spine surgery, with OP being a possible consequence of AS. However, the mechanism of AS-induced OP (AS-OP) remains unknown, limiting etiologic research and therapy of the illness. To mine targetable medicine for the prevention and treatment of AS-OP, this study analyzes public data sets using bioinformatics to identify genes and biological pathways relevant to AS-OP. METHODS: First, text mining was used to identify common genes associated with AS and OP, after which functional analysis was carried out. The STRING database and Cytoscape software were used to create protein-protein interaction networks. Hub genes and potential drugs were discovered using drug-gene interaction analysis and transcription factors-gene interaction analysis. RESULTS: The results of text mining showed 241 genes common to AS and OP, from which 115 key symbols were sorted out by functional analysis. As options for treating AS-OP, protein-protein interaction analysis yielded 20 genes, which may be targeted by 13 medications. CONCLUSIONS: Carlumab, bermekimab, rilonacept, rilotumumab, and ficlatuzumab were first identified as the potential drugs for the treatment of AS-OP, proving the value of text mining and pathway analysis in drug discovery.

Inhibition of IL1R1 or CASP4 attenuates spinal cord injury through ameliorating NLRP3 inflammasome-induced pyroptosis.

Spinal cord injury (SCI) is a devastating trauma characterized by serious neuroinflammation and permanent neurological dysfunction. However, the molecular mechanism of SCI remains unclear, and few effective medical therapies are available at present. In this study, multiple bioinformatics methods were used to screen out novel targets for SCI, and the mechanism of these candidates during the progression of neuroinflammation as well as the therapeutic effects were both verified in a rat model of traumatic SCI. As a result, CASP4, IGSF6 and IL1R1 were identified as the potential diagnostic and therapeutic targets for SCI by computational analysis, which were enriched in NF-κB and IL6-JAK-STATA3 signaling pathways. In the injured spinal cord, these three signatures were up-regulated and closely correlated with NLRP3 inflammasome formation and gasdermin D (GSDMD) -induced pyroptosis. Intrathecal injection of inhibitors of IL1R1 or CASP4 improved the functional recovery of SCI rats and decreased the expression of these targets and inflammasome component proteins, such as NLRP3 and GSDMD. This treatment also inhibited the pp65 activation into the nucleus and apoptosis progression. In conclusion, our findings of the three targets shed new light on the pathogenesis of SCI, and the use of immunosuppressive agents targeting these proteins exerted anti-inflammatory effects against spinal cord inflammation by inhibiting NF-kB and NLRP3 inflammasome activation, thus blocking GSDMD -induced pyroptosis and immune activation.

Functional traits underlying performance variations in the overwintering of the cosmopolitan invasive plant water hyacinth (Eichhornia crassipes) under climate warming and water drawdown.

Reports of the Intergovernmental Panel on Climate Change (IPCC) indicate that temperature rise is still the general trend of the global climate in the 21st century. Invasive species may benefit from the increase in temperature, as climate can be viewed as a resource, and the increase in the available resources favors the invasibility of invasive species. This study aimed to assess the overwintering growth of the cosmopolitan invasive plant water hyacinth (Eichhornia crassipes) at its northern boundary. Using E. crassipes as a model plant, a cross-year mesocosm experiment was conducted to determine 17 plant functional traits, including growth, morphological, root topological, photosynthetic, and stoichiometric traits, under climate warming (ambient, temperature rises of 1.5°C and 3.0°C), and water drawdown or water withdrawal (water depths of 1, 10, and 20 cm) treatments. The overwintering growth of E. crassipes was facilitated by climate warming and proper water drawdown, and climate warming played a leading role. A temperature rises of 3.0°C and a water depth of 10 cm were the most suitable conditions for the overwintering and rooting behavior of the plant. Controlling the temperature to within 1.5°C, an ambitious goal for China, still facilitated the overwintering of E. crassipes. With climate warming, the plant can overwinter successfully, which possibly assists it in producing and spreading new ramets in the vernal flood season. The new rooting behavior induced by ambient low temperature may be viewed as a unique growth adaptation strategy for a niche change, as it helps these plants invade empty niches left by dead free-floating plants on the water surface following winter freezes. With continued global warming, the distribution of the plant may expand northward, and eradication of the plant during the winter water drawdown period may be a more effective strategy.

Families Playing Animal Crossing Together: Coping With Video Games During the COVID-19 Pandemic.

The COVID-19 pandemic was stressful for everyone, particularly for families who had to supervise and support children, facilitate remote schooling, and manage work and home life. We consider how families coped with pandemic-related stress using the video game Animal Crossing: New Horizons. Combining a family coping framework with theorizing about media as a coping tool, this interview study of 27 families (33 parents and 37 children) found that parents and children individual coped with pandemic-related stress with media. Parents engaged in protective buffering of their children with media, taking on individual responsibility to cope with a collective problem. Families engaged in communal coping, whereby media helped the family cope with a collective problem, taking on shared ownership and responsibility. We provide evidence for video games as coping tools, but with the novel consideration of family coping with media.

Effect of juvenile omni-benthivorous fish (Carassius carassius) disturbance on the efficiency of lanthanum-modified bentonite (LMB) for eutrophication control: a mesocosm study.

Lanthanum-modified bentonite (LMB) is widely used for eutrophication control and has demonstrated good efficiency in some eutrophic lakes. However, the efficiency of LMB on eutrophication control in some eutrophic lakes, where the structure of food webs is mainly dominated by omni-benthivorous fish, remains ambiguous. Omni-benthivorous fish usually disturbs sediment and promotes the release of internal nutrients, the effect of which on the efficacy of LMB remains to be studied. Thus, a 30-day mesocosm experiment was conducted to determine whether omni-benthivorous fish disturbance and LMB would cause antagonistic responses. LMB significantly reduced dissolved P concentration in overlying water, converting mobile P to bound P in the surface layer of sediment in the absence of crucian carp (Carassius carassius). However, there were significantly negative interaction effects between LMB and crucian carp. Although LMB still effectively reduced the total dissolved phosphorus (TDP) and soluble reactive phosphorus (SRP) concentrations of overlying water in the presence of crucian carp, it had limited efficacy on inhibiting the increased concentrations of suspended solids, particulate nutrients, and chlorophyll a (Chl a) due to crucian carp disturbance. Furthermore, the crucian carp disturbance also increased the risk of mobile P releasing from surface sediment, whether with or without LMB application. The results indicated that the efficacy of LMB was insufficient to offset the negative effect of omni-benthivorous fish disturbance on eutrophication control. Hence, the omni-benthivorous fish also need to be considered for eutrophication control in shallow eutrophic lakes. Some measures need to be taken to control the biomass of omni-benthivorous fish.

Transformation of Aquatic Plant Diversity in an Environmentally Sensitive Area, the Lake Taihu Drainage Basin.

Located downstream of the Yangtze River Delta, the Lake Taihu drainage basin (LTDB) is one of the most developed areas in China. This area currently faces population and development issues, as well as many environmental problems, such as cultural eutrophication, algal blooms, and loss of native aquatic plants. Changes in aquatic biodiversity have received less attention than have changes in terrestrial habitats because relevant observations are lacking. In this study, information from 2010, 2014, and 2018 concerning the transformation of the aquatic plant biodiversity was obtained. The results showed that the dominant aquatic plants have changed from native plants to invasive plants. Aquatic plant biodiversity showed a decreasing trend, which may reduce the freshwater ecosystem function, and anthropogenic activities accounted for these changes. How to prevent the decline in aquatic plants and control the invasion of introduced aquatic plants should be a priority in the management of aquatic plants in the LTDB.

Turning up the heat: warming influences plankton biomass and spring phenology in subtropical waters characterized by extensive fish omnivory.

Understanding how biological communities respond to climate change is a major challenge in ecology. The response of ectotherms to changes in temperature depends not only on their species-specific thermal tolerances but also on temperature-mediated interactions across different trophic levels. Warming is predicted to reinforce trophic cascades in linear aquatic food chains, but little is known about how warming might affect the lower trophic levels of food webs involving extensive fish omnivory, a common scenario in subtropical and tropical waterbodies. In this study, a mesocosm warming experiment was conducted involving a pelagic food chain (fish-zooplankton-phytoplankton) topped by the omnivorous bighead carp [Aristichthys nobilis (Richardson)]. We found that temperature elevation significantly enhanced the growth of fish and suppressed zooplankton, including both metazooplankton and ciliates, while abundances of phytoplankton, despite disruption of temporal dynamics, did not increase correspondingly-likely due to fish predation. Our results suggest that trophic cascades are less unlikely to be reinforced by warming in food chains involving significant omnivory. Moreover, we found that warming advanced the spring abundance peak of phytoplankton abundance and that of the parthenogenetic rotifer Brachionus quadridentatus; whereas, it had no effect on the only sexually reproducing copepod, Mesocyclops leuckarti, presumably due to its prolonged life history. Our study also confirmed that warming may lead to a phenological mismatch between some predators and their prey because of the distinct life histories among taxa, with potentially severe consequences for resource flow in the food chain, at least in the short term.

Hepatitis C virus genotypes 1-3 infections regulate lipogenic signaling and suppress cholesterol biosynthesis in hepatocytes.

BACKGROUND: Patients with different hepatitis C virus (HCV) genotype infections are associated with varying metabolic disorders. Although alteration of lipid metabolism has been confirmed as a virus-induced metabolic derangement in chronic hepatitis C patients, the impact of various HCV genotypes on hepatic cholesterol metabolism remains elusive. In this study, we thus investigated the HCV genotype-specific lipogenic and cholesterol metabolism profiles in an in vitro cell culture system. METHODS: We first conducted HCV cell culture system (HCVcc) assays by infecting Huh7.5.1 cells with multiple infection-competent HCV strains, including the genotype 2a JFH1 and JFH1-based intergenotypic recombinants 1b and 3a. We then examined the expression levels of various lipid and cholesterol-related genes. RESULTS: The data showed that infection with individual HCV genotypes exerted unique gene expression regulatory effects on lipoproteins and cholesterol metabolism genes. Of note, all HCV strains suppressed cholesterol biosynthesis in hepatocytes through downregulating the expression of HMG-CoA reductase (HMGCR) and farnesyl-diphosphate farnesyltransferase 1 (FDFT1) - two essential enzymes for cholesterol biosynthesis. These HCV-mediated inhibitory effects could be reversed by treatment with sofosbuvir, a pangenotypic NS5B inhibitor. In addition, overexpression of HCV genotype 1b, 2a or 3a core protein significantly suppressed HMGCR mRNA transcription and translation, thus diminished cellular cholesterol biosynthesis. Nonetheless, the core protein had no effect on FDFT1 expression. CONCLUSION: Although HCV infection regulates host lipid metabolism in a genotype-specific manner, its inhibition on hepatocellular cholesterogenic gene expression and total cholesterol biosynthesis is a common effect among HCV genotype 1b, 2a and 3a.

Controlling for Participants' Viewing Distance in Large-Scale, Psychophysical Online Experiments Using a Virtual Chinrest.

While online experiments have shown tremendous potential to study larger and more diverse participant samples than is possible in the lab, the uncontrolled online environment has prohibited many types of psychophysical studies due to difficulties controlling the viewing distance and stimulus size. We introduce the Virtual Chinrest, a method that measures a participant's viewing distance in the web browser by detecting a participant's blind spot location. This makes it possible to automatically adjust stimulus configurations based on an individual's viewing distance. We validated the Virtual Chinrest in two laboratory studies in which we varied the viewing distance and display size, showing that our method estimates participants' viewing distance with an average error of 3.25 cm. We additionally show that by using the Virtual Chinrest we can reliably replicate measures of visual crowding, which depends on a precise calculation of visual angle, in an uncontrolled online environment. An online experiment with 1153 participants further replicated the findings of prior laboratory work, demonstrating how visual crowding increases with eccentricity and extending this finding by showing that young children, older adults and people with dyslexia all exhibit increased visual crowding, compared to adults without dyslexia. Our method provides a promising pathway to web-based psychophysical research requiring controlled stimulus geometry.