Regulation of Antioxidant Nrf2 Signaling: An Important Pathway in COPD

: Inflammatory bowel disease (IBD) has stimulated much interest due to its surging incidences and health impacts in the U.S. and worldwide. However, the exact cause of IBD remains incompletely understood, and biomarker is lacking towards early diagnostics and effective therapy assessment. To tackle these, the emerging high-resolution mass spectrometry (HRMS)-based metabolomics shows promise. Here, we conducted a pilot untargeted LC/MS metabolomic profiling in Crohn’s disease, for which serum samples of both active and inactive cases were collected, extracted, and profiled by a state-of-the-art compound identification workflow. Results show a distinct metabolic profile of Crohn’s from control, with most metabolites downregulated. The identified compounds are structurally diverse, pointing to important pathway perturbations ranging from energy metabolism (e.g., β-oxidation of fatty acids) to signaling cascades of lipids (e.g., DHA) and amino acid (e.g., L-tryptophan). Importantly, an integral role of gut microbiota in the pathogenesis of Crohn’s disease is highlighted. Xenobiotics and their biotransformants were widely detected, calling for massive exposomic profiling for future cohort studies as such. This study endorses the analytical capacity of untargeted metabolomics for biomarker development, cohort stratification, and mechanistic interpretation; the findings might be valuable for advancing biomarker research and etiologic inquiry in IBD.

Download Full-text

Gossip about Coronavirus: Infection status and norm adherence shape social responses

Group Processes & Intergroup Relations ◽

10.1177/1368430221991232 ◽

2021 ◽

Vol 24 (4) ◽

pp. 658-679

Author(s):

Terence D. Dores Cruz ◽

Romy van der Lee ◽

Bianca Beersma

Keyword(s):

Social Exclusion ◽

Behavioral Intentions ◽

Infection Risk ◽

Infection Status ◽

Social Responses ◽

Social Distancing ◽

Important Pathway ◽

Group Members ◽

Coronavirus Infection

To stop the spread of the Coronavirus, people must avoid infection risk. Given widespread skepticism regarding information concerning the Coronavirus received from authorities, one potentially important pathway to estimate the infectiousness of one’s group members could be through gossip (i.e., information about an absent target). Infection risk is reflected by both infection status and adherence to social distancing norms. In hypothetical scenarios ( N = 837), participants received gossip that we manipulated to describe a group member’s infection status and/or norm adherence. Results showed people tended to believe gossip and that gossip influenced behavioral intentions to avoid and punish targets of gossip as well as the perception of targets. We conclude that gossip, while potentially unreliable, could affect how people treat group members. We discuss how gossip could alleviate the Coronavirus crisis by contributing to slowing the Coronavirus’s spread, as well as exacerbate it through increased social exclusion based on unverified information.

Download Full-text

Androgen Receptor Signaling in Prostate Cancer Genomic Subtypes

Cancers ◽

10.3390/cancers13133272 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3272

Author(s):

Lauren K. Jillson ◽

Gabriel A. Yette ◽

Teemu D. Laajala ◽

Wayne D. Tilley ◽

James C. Costello ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Targeted Therapies ◽

Meta Analysis ◽

Therapy Resistance ◽

Androgen Receptor Signaling ◽

Genomic Changes ◽

Risk Patients ◽

Important Pathway ◽

Therapy Option

While many prostate cancer (PCa) cases remain indolent and treatable, others are aggressive and progress to the metastatic stage where there are limited curative therapies. Androgen receptor (AR) signaling remains an important pathway for proliferative and survival programs in PCa, making disruption of AR signaling a viable therapy option. However, most patients develop resistance to AR-targeted therapies or inherently never respond. The field has turned to PCa genomics to aid in stratifying high risk patients, and to better understand the mechanisms driving aggressive PCa and therapy resistance. While alterations to the AR gene itself occur at later stages, genomic changes at the primary stage can affect the AR axis and impact response to AR-directed therapies. Here, we review common genomic alterations in primary PCa and their influence on AR function and activity. Through a meta-analysis of multiple independent primary PCa databases, we also identified subtypes of significantly co-occurring alterations and examined their combinatorial effects on the AR axis. Further, we discussed the subsequent implications for response to AR-targeted therapies and other treatments. We identified multiple primary PCa genomic subtypes, and given their differing effects on AR activity, patient tumor genetics may be an important stratifying factor for AR therapy resistance.

Download Full-text

Targeting Hedgehog Signalling through the Ubiquitylation Process: The Multiple Roles of the HECT-E3 Ligase Itch

Cells ◽

10.3390/cells8020098 ◽

2019 ◽

Vol 8 (2) ◽

pp. 98 ◽

Cited By ~ 9

Author(s):

Paola Infante ◽

Ludovica Lospinoso Severini ◽

Flavia Bernardi ◽

Francesca Bufalieri ◽

Lucia Di Marcotullio

Keyword(s):

E3 Ligase ◽

Multiple Roles ◽

Post Translational Modification ◽

Therapeutic Approaches ◽

Cellular Functions ◽

Hedgehog Signalling ◽

Promising Target ◽

Important Pathway ◽

Multiple Levels

Hedgehog signalling (Hh) is a developmental conserved pathway strongly involved in cancers when deregulated. This important pathway is orchestrated by numerous regulators, transduces through distinct routes and is finely tuned at multiple levels. In this regard, ubiquitylation processes stand as essential for controlling Hh pathway output. Although this post-translational modification governs proteins turnover, it is also implicated in non-proteolytic events, thereby regulating the most important cellular functions. The HECT E3 ligase Itch, well known to control immune response, is emerging to have a pivotal role in tumorigenesis. By illustrating Itch specificities on Hh signalling key components, here we review the role of this HECT E3 ubiquitin ligase in suppressing Hh-dependent tumours and explore its potential as promising target for innovative therapeutic approaches.

Download Full-text

Stormwater management in a catchbasin perspective - best practices or sustainable strategies?

Water Science & Technology ◽

10.2166/wst.2002.0675 ◽

2002 ◽

Vol 46 (6-7) ◽

pp. 159-166 ◽

Cited By ~ 5

Author(s):

M. Bäckström ◽

P.-A. Malmqvist ◽

M. Viklander

Keyword(s):

Best Management Practices ◽

Stormwater Management ◽

Management Practices ◽

Pollutant Removal ◽

Best Management ◽

Environmental Objectives ◽

Important Pathway ◽

Pollutant Sources ◽

Pollutant Source ◽

The Eu

A strategy for sustainable stormwater management is needed. This study has focused on the relative importance of stormwater as a pollutant source in a catchbasin, if Best Management Practices (BMPs) result in pollutant removal or pollutant redistribution, and methods for screening of stormwater strategies. Stormwater is most likely an important pathway for pollutants in a catchbasin perspective. True pollutant removal can only be achieved if the pollutant sources are eliminated. Until that is reached, we should have the best possible control of the pollutant fluxes in the watershed. This study indicates that the search for a sustainable stormwater strategy could be easier to handle if different “screens” could be used. The Swedish environmental objectives, which try to encapsulate all aspects of sustainability, may be used as a foundation for a “sustainability screen”. By using this screen, the “unsustainable” features of different stormwater strategies could be pointed out. A “standards and legislation screen” will be based on the EU Water Framework Directive. As this study has shown, it is doubtful whether the conventional BMPs, such as stormwater ponds and infiltration facilities, produce a sufficient pollutant control.

Download Full-text

Heterologous Expression of Lysergic Acid and Novel Ergot Alkaloids in Aspergillus fumigatus

Applied and Environmental Microbiology ◽

10.1128/aem.02137-14 ◽

2014 ◽

Vol 80 (20) ◽

pp. 6465-6472 ◽

Cited By ~ 21

Author(s):

Sarah L. Robinson ◽

Daniel G. Panaccione

Keyword(s):

Aspergillus Fumigatus ◽

Candidate Genes ◽

Mass Spectra ◽

Ergot Alkaloids ◽

Lysergic Acid ◽

Precursor Feeding ◽

Gene Encoding ◽

Content Type ◽

Multiple Reactions ◽

Important Pathway

ABSTRACTDifferent lineages of fungi produce distinct classes of ergot alkaloids. Lysergic acid-derived ergot alkaloids produced by fungi in the Clavicipitaceae are particularly important in agriculture and medicine. The pathway to lysergic acid is partly elucidated, but the gene encoding the enzyme that oxidizes the intermediate agroclavine is unknown. We investigated two candidate agroclavine oxidase genes from the fungusEpichloë festucaevar.lolii×Epichloë typhinaisolate Lp1 (henceforth referred to asEpichloësp. Lp1), which produces lysergic acid-derived ergot alkaloids. Candidate geneseasHandcloAwere expressed in a mutant strain of the moldAspergillus fumigatus, which typically produces a subclass of ergot alkaloids not derived from agroclavine or lysergic acid. Candidate genes were coexpressed with theEpichloësp. Lp1 allele ofeasA, which encodes an enzyme that catalyzed the synthesis of agroclavine from anA. fumigatusintermediate; the agroclavine then served as the substrate for the candidate agroclavine oxidases. Strains expressingeasAandcloAfromEpichloësp. Lp1 produced lysergic acid from agroclavine, a process requiring a cumulative six-electron oxidation and a double-bond isomerization. Strains that accumulated excess agroclavine (as a result ofEpichloësp. Lp1easAexpression in the absence ofcloA) metabolized it into two novel ergot alkaloids for which provisional structures were proposed on the basis of mass spectra and precursor feeding studies. Our data indicate that CloA catalyzes multiple reactions to produce lysergic acid from agroclavine and that combining genes from different ergot alkaloid pathways provides an effective strategy to engineer important pathway molecules and novel ergot alkaloids.

Download Full-text

Importance of Different Pathways for Maize Kernel Infection by Fusarium moniliforme

Phytopathology ◽

10.1094/phyto.1997.87.2.209 ◽

1997 ◽

Vol 87 (2) ◽

pp. 209-217 ◽

Cited By ~ 155

Author(s):

G. P. Munkvold ◽

D. C. McGee ◽

W. M. Carlton

Keyword(s):

Fusarium Moniliforme ◽

Field Experiments ◽

Systemic Infection ◽

Seed Transmission ◽

Maize Hybrids ◽

Systemic Movement ◽

Kernel Infection ◽

Important Pathway ◽

Infection Pathways ◽

Systemic Development

The relative importance of several infection pathways (silks, stalks, and seed) leading to kernel infection of maize hybrids by Fusarium moniliforme was investigated in field experiments in 1993 and 1994. Systemic movement of specific fungal strains within plants was detected by using vegetative compatibility as a marker. Transmission of F. moniliforme from inoculated seed to stalks and developing kernels was detected in two of three field experiments; the seed-inoculated strain was detected in kernels on approximately 10% of ears. The percentage of kernels infected with the seed-inoculated strain ranged from 0 to 70%, with a mean of 0 to 2.5% (0 to 8.3% of F. moniliforme-infected kernels). Other pathways to kernel infection were more effective than seed transmission and systemic infection. F. moniliforme strains inoculated into the crowns and stalks of plants were found throughout the stalks and in up to 95% of the kernels in individual plants. Infection through the silks was clearly the most effective pathway to kernel infection. This was the only inoculation method that significantly increased overall incidence of F. moniliforme infection in kernels; the silk-inoculated strain infected up to 100% of the kernels in individual ears, with a treatment mean as high as 83.7% of kernels. When plants were silk-inoculated, the percentage of kernels infected by other F. moniliforme strains from the seed or stalk was reduced, apparently due to competition among strains. This study provides evidence that systemic development of F. moniliforme from maize seed and stalk infections can contribute to kernel infection, but silk infection is a more important pathway for this fungus to reach the kernels.

Download Full-text

DETERMINATION OF NATURAL RADIONUCLIDE IN PIG PRODUCTION CHAIN IN MACEDONIA BY GAMMA SPECTROMETRY

AGROFOR ◽

10.7251/agreng1601151n ◽

2016 ◽

Vol 1 (1) ◽

Author(s):

Dimitar Nakov ◽

Metodija Trajchev ◽

Aleksandra Angjeleska ◽

Katerina Belichovska ◽

Nikola Pacinovski

Keyword(s):

Specific Radioactivity ◽

Natural Radionuclide ◽

Animal Products ◽

Production Chain ◽

Significant Difference ◽

Human Food Chain ◽

Naturally Occurring Radionuclides ◽

Result Show ◽

Important Pathway

Exposure of animals to ionizing irradiation may be a important pathway fortransfer of radionuclides to human food chain, thereby adding to the exposureburden. Therefore, radiation control of animal feeds and animal products willreduce risk for radioactive hazards to human health. The study was carried out inorder to detect the natural radioactivity in edible parts of pigs, excrements andfeeds in one commercial pig breeding farm in Macedonia. Therefore, 40K, 212Pb,214Pb, 228Ac, 235U, 241Am, 212Bi, 214Bi, 232Th, 7Be and 226Ra were measured usinggamma spectrometry. Gamma spectrometer Canberra Packard with a high-puritygermanium detector and Marinelli beakers (1 l capacity) were used for the samplesmeasurement. The most prominent gamma energies observed in the spectrabelonged to the naturally occurring radionuclides 40K, 235U and 232Th. Othernuclides if present occurred infrequently at low levels. The result show that 40Kmade the largest contribution to the specific radioactivity in all the samples. Themean activity concentration of the 40K in edible organs (kidney and liver), muscle,excrements and feeds was: 73.39±9.109 Bq/kg; 111.26±3.88 Bq/kg; 298.80±38.51Bq/kg; 83.60±10.279 Bq/kg, respectively. The 235U and 232Th were detectible onlyin feed samples (0.53±0.293 Bq/kg; 163.69±23.791 Bq/kg, respectively) andsamples from excrements (0.25±0.021 Bq/kg; 58.17±1.062 Bq/kg, respectively).The other radionuclides were detected only in few samples and the measuredactivities were below the detection limit. If we take in consideration the activityconcentration of the most frequently occurred 40K found in all samples, than therewas statistical significant difference between radioactivity concentration in organs,muscle, excrements and feeds (p<0.001).

Download Full-text

Strong degradation of palsas and peat plateaus in northern Norway during the last 60 years

10.5194/tc-2016-12 ◽

2016 ◽

Cited By ~ 6

Author(s):

Amund F. Borge ◽

Sebastian Westermann ◽

Ingvild Solheim ◽

Bernd Etzelmüller

Keyword(s):

Aerial Imagery ◽

Aerial Images ◽

Moderate Increase ◽

Permafrost Degradation ◽

Northern Norway ◽

Temperature And Precipitation ◽

Important Pathway ◽

The 1950S ◽

Lateral Erosion ◽

Peat Plateaus

Abstract. Palsas and peat plateaus are permafrost landforms occurring in subarctic mires which constitute sensitive ecosystems with strong significance for vegetation, wildlife, hydrology and carbon cycle. We have systematically mapped the occurrence of palsas and peat plateaus in the northernmost county of Norway (Finnmark, ~ 50 000 km2) by manual interpretation of aerial images from 2005–2014 at a spatial resolution of 250 m2. At this resolution, mires and wetlands with palsas or peat plateaus occur in about 850 km2 of Finnmark, with the actual palsas and peat plateaus underlain by permafrost covering a surface area of approximately 110 km2. Secondly, we have quantified the lateral changes of the extent of palsas and peat plateaus for four study areas located along a NW–SE transect through Finnmark by utilizing repeat aerial imagery from the 1950s to the 2010s. The results of the lateral changes reveal a total decrease of 33–71 % in the areal extent of palsas and peat plateaus during the study period, with the largest lateral change rates observed in the last decade. However, the results indicate that degradation of palsas and peat plateaus in northern Norway has been a consistent process during the second half of the 20th century and possibly even earlier. Significant rates of degradation are observed in all investigated time periods since the 1950s, and thermokarst landforms observed on aerial images from the 1950s suggest that lateral degradation was already an ongoing process at this time. The results of this study show that lateral erosion of palsas and peat plateaus is an important pathway for permafrost degradation in the sporadic permafrost zone in northern Scandinavia. While the environmental factors governing the rate of erosion are not yet fully understood, we note a moderate increase in both air temperature and precipitation during the last few decades in the region.

Download Full-text

Tongxinluo Exerts Inhibitory Effects on Pyroptosis and Amyloid-β Peptide Accumulation after Cerebral Ischemia/Reperfusion in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/5788602 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Bing Wang ◽

Zhongkuan Lyu ◽

Yuanjin Chan ◽

Qiyue Li ◽

Li Zhang ◽

...

Keyword(s):

Cerebral Ischemia ◽

Ischemia Reperfusion ◽

Amyloid Β ◽

Amyloid Β Peptide ◽

Protective Effects ◽

Glymphatic System ◽

Pyrin Domain ◽

Cerebral Ischemia Reperfusion ◽

Potential Possibility ◽

Important Pathway

Amyloid-β peptide (Aβ) accumulation is a detrimental factor in cerebral ischemia/reperfusion (I/R) injuries accounting for dementia induced by ischemic stroke. In addition to blood brain barrier (BBB), the glymphatic system mediated by aquaporin-4 (AQP-4) on astrocytic endfeet functions as an important pathway for the clearance of Aβ in the brain. Cerebral I/R induced astrocytic pyroptosis potentially causes the AQP-4 polarization loss and dysfunctional BBB-glymphatic system exacerbating the accumulation of Aβ. Furthermore, Aβ toxicity has been identified as a trigger of pyroptosis and BBB damage, suggesting an amplified effect of Aβ accumulation after cerebral I/R. Therefore, based on our previous work, this study was designed to explore the intervention effects of Tongxinluo (TXL) on astrocytic pyroptosis and Aβ accumulation after cerebral I/R in rats. The results showed that TXL intervention obviously alleviated the degree of pyroptosis by downregulating expression levels of cleaved caspase-11/1, N-terminal gasdermin D, nucleotide-binding oligomerization domain-like receptors pyrin domain containing 3 (NLRP3), interleukin-6 (IL-6), and cleaved IL-1β and abated astrocytic pyroptosis after cerebral I/R. Moreover, TXL intervention facilitated to restore AQP-4 polarization and accordingly relieve Aβ accumulation around astrocytes in ischemic cortex and hippocampus as well as the formation of toxic Aβ (Aβ1–42 oligomer). Our study indicated that TXL intervention could exert protective effects on ischemic brain tissues against pyroptotic cell death, inhibit astrocytic pyroptosis, and reduce toxic Aβ accumulation around astrocytes in cerebral I/R injuries. Furthermore, our study provides biological evidence for the potential possibility of preventing and treating poststroke dementia with TXL in clinical practice.

Download Full-text