Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

Our Lord said, “If any man will come after Me, let him deny himself, pick up his cross and follow Me.” The church of Jesus Christ, of course, is

Our Lord said, “If any man will come after Me, let him deny himself, pick up his cross and follow Me.” The church of Jesus Christ, of course, is

What a privilege and joy it is to worship the Lord here at Grace church. Patricia and I miss it when we’re not here; there&rsqu

Earlier in the service I read from the first chapter of Romans what is really a very, very shocking portion of Scripture just to remind you that Romans cha

The following sermon transcript does not match the video version of the sermon—it matches only the audio version. Here's a brief exp

No fewer than 971 Nigerians were abducted across the country in October 2024, DAILY POST learnt. The revelation is coming amid the emergence of a new terror group, ‘Lakurawa’ in the northwestern part of the country. The data is contained in the ‘October 2024 Nigeria Security Report’ by Beacon Security and Intelligence Limited, BSIL, a […]

Over 971 Nigerians abducted in October 2024 – Report

Taiwan was on "alert" as it detected a Chinese aircraft carrier to its south on Sunday, the self-ruled island's defense ministry said.

It is still unclear if Eliezer Feldstein, the PM's media team advisor suspected of leaking the documents, did so at the prime minister's orders.

The decision of Israel’s parliament, the Knesset, to adopt two laws that would severely limit or outright ban UNRWA has the potential to set a dangerous precedent, where countries can simply implement their own justification to ban the activity of the United Nations, even if it violates their obligations under international humanitarian law. Even with […]

The problem of sin isn’t fundamentally external. It’s most visible in our actions, but our actions are merely the manifestation of a corruption that comes from within.

Gang violence has ravaged Haiti, causing thousands of civilian deaths, displacements, and violations of international humanitarian law. Turmoil is expected to escalate following the removal of Haitian Prime Minister Garry Conille from office on November 11. On November 10, the Haitian government announced plans to replace incumbent prime minister Conille, with entrepreneur and former senate […]

More European Central Bank interest rate cuts are coming and the deposit rate could hit the so-called neutral level in the first half of next year, Finnish central bank chief Olli Rehn said on Tuesday. The ECB has already cut rates three times this year as prices have fallen and further cuts at each of […]

to write everlasting characters english edition

Microwaves in homes, offices and laboratories have been found to host diverse microbiomes, highlighting the importance of regular cleaning

Cyanobacteria exposed to shorter days are better at surviving cold conditions, showing that even simple organisms can prepare for the arrival or summer and winter

Bacteria that have been genetically engineered to work like computers can solve a range of problems, using a very simple type of artificial intelligence

The natural motors that power tail-like appendages in bacteria seem to have a single evolutionary origin, allowing parts from different species to be combined to create a tiny new engine

Rival tribes of bacteria armed with poison darts are fighting it out in your gut, with armies of traitors often winning the day

Geologists hoping to declare a new epoch dominated by humanity’s influence on Earth have chosen Crawford Lake in Canada as the location where the start of the Anthropocene is defined

Companies are searching all over the world for deposits of geologic hydrogen that could be used as clean fuel, and a mine in Albania could give them clues about where to look

Microbes that rapidly convert CO2 to rock could lock away the greenhouse gas in deep underground storage sites, such as depleted oil and gas reservoirs

Experts predict that the number of cancer cases around the world will skyrocket, resulting in millions more fatalities by 2050

Why childhood is so protracted has long been mysterious, now a spate of archaeological discoveries suggest an intriguing explanation

Title: Germ-Infected Mosquitoes Can't Spread Dengue
Category: Health News
Created: 8/25/2011 11:01:00 AM
Last Editorial Review: 8/25/2011 12:00:00 AM

Title: Antibiotic Overuse May Be Bad for Body's Good Bacteria
Category: Health News
Created: 8/25/2011 11:01:00 AM
Last Editorial Review: 8/25/2011 12:00:00 AM

Title: Could Bacteria in Skin Mites Help Cause Rosacea?
Category: Health News
Created: 8/30/2012 10:05:00 AM
Last Editorial Review: 8/30/2012 12:00:00 AM

Title: Your Gut Bacteria May Predict Your Obesity Risk
Category: Health News
Created: 8/28/2013 2:35:00 PM
Last Editorial Review: 8/29/2013 12:00:00 AM

Title: Study: Young Adults Who Had Depression Have 'Hyper-Connected' Brain Networks
Category: Health News
Created: 8/27/2014 2:36:00 PM
Last Editorial Review: 8/28/2014 12:00:00 AM

Title: FDA OKs New Antibacterial Drug
Category: Health News
Created: 8/31/2017 12:00:00 AM
Last Editorial Review: 8/31/2017 12:00:00 AM

Title: Babies of Opioid-Addicted Moms May Struggle in School
Category: Health News
Created: 8/30/2018 12:00:00 AM
Last Editorial Review: 8/30/2018 12:00:00 AM

Title: Climate Change Hiking Danger of Flesh-Eating Bacteria Infections
Category: Health News
Created: 8/23/2019 12:00:00 AM
Last Editorial Review: 8/26/2019 12:00:00 AM

Title: A Third of Americans Were Infected With COVID-19 in 2020: Study
Category: Health News
Created: 8/26/2021 12:00:00 AM
Last Editorial Review: 8/27/2021 12:00:00 AM

Title: SIBO (Small Intestinal Bacterial Overgrowth)
Category: Diseases and Conditions
Created: 10/28/2005 12:00:00 AM
Last Editorial Review: 8/8/2022 12:00:00 AM

Somatic mutations arise and accumulate during tissue culture and vegetative propagation, potentially affecting various traits in horticultural crops, but their characteristics are still unclear. Here, somatic mutations in regenerated woodland strawberry derived from tissue culture of shoot tips under different conditions and 12 cultivated strawberry individuals are analyzed by whole genome sequencing. The mutation frequency of single nucleotide variants is significantly increased with increased hormone levels or prolonged culture time in the range of 3.3 x 10^–8–3.0 x 10^–6 mutations per site. CG methylation shows a stable reduction (0.71%–8.03%) in regenerated plants, and hypoCG-DMRs are more heritable after sexual reproduction. A high-quality haplotype-resolved genome is assembled for the strawberry cultivar "Beni hoppe." The 12 "Beni hoppe" individuals randomly selected from different locations show 4731–6005 mutations relative to the reference genome, and the mutation frequency varies among the subgenomes. Our study has systematically characterized the genetic and epigenetic variants in regenerated woodland strawberry plants and different individuals of the same strawberry cultivar, providing an accurate assessment of somatic mutations at the genomic scale and nucleotide resolution in plants.

End-to-end RNA-sequencing methods that capture 5'-sequence content without cumbersome library manipulations are of great interest, particularly for analysis of long RNAs. While template-switching methods have been developed for RNA sequencing by distributive short-read RTs, such as the MMLV RTs used in SMART-Seq methods, they have not been adapted to leverage the power of ultraprocessive RTs, such as those derived from group II introns. To facilitate this transition, we dissected the individual processes that guide the enzymatic specificity and efficiency of the multistep template-switching reaction carried out by RTs, in this case, by MarathonRT. Remarkably, this is the first study of its kind, for any RT. First, we characterized the nucleotide specificity of nontemplated addition (NTA) reaction that occurs when the RT extends past the RNA 5'-terminus. We then evaluated the binding specificity of specialized template-switching oligonucleotides, optimizing their sequences and chemical properties to guide efficient template-switching reaction. Having dissected and optimized these individual steps, we then unified them into a procedure for performing RNA sequencing with MarathonRT enzymes, using a well-characterized RNA reference set. The resulting reads span a six-log range in transcript concentration and accurately represent the input RNA identities in both length and composition. We also performed RNA-seq from total human RNA and poly(A)-enriched RNA, with short- and long-read sequencing demonstrating that MarathonRT enhances the discovery of unseen RNA molecules by conventional RT. Altogether, we have generated a new pipeline for rapid, accurate sequencing of complex RNA libraries containing mixtures of long RNA transcripts.

The SARS-CoV-2 frameshifting element (FSE) has been intensely studied and explored as a therapeutic target for coronavirus diseases, including COVID-19. Besides the intriguing virology, this small RNA is known to adopt many length-dependent conformations, as verified by multiple experimental and computational approaches. However, the role these alternative conformations play in the frameshifting mechanism and how to quantify this structural abundance has been an ongoing challenge. Here, we show by DMS and dual-luciferase functional assays that previously predicted FSE mutants (using the RAG graph theory approach) suppress structural transitions and abolish frameshifting. Furthermore, correlated mutation analysis of DMS data by three programs (DREEM, DRACO, and DANCE-MaP) reveals important differences in their estimation of specific RNA conformations, suggesting caution in the interpretation of such complex conformational landscapes. Overall, the abolished frameshifting in three different mutants confirms that all alternative conformations play a role in the pathways of ribosomal transition.

Background

Exacerbations of noncystic fibrosis bronchiectasis (bronchiectasis) are associated with reduced health-related quality of life and increased mortality, likelihood of hospitalisation and lung function decline. This study investigated patient clinical characteristics associated with exacerbation frequency.

Organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 are important hepatic transporters. We previously identified OATP1B3 being critically implicated in the disposition of abiraterone. We aimed to further investigate the effects of abiraterone on the activities of OATP1B1 and OATP1B3 utilizing a validated endogenous biomarker coproporphyrin I (CP-I). We used OATP1B-transfected cells to characterize the inhibitory potential of abiraterone against OATP1B-mediated uptake of CP-I. Inhibition constant (K_i) was incorporated into our physiologically based pharmacokinetic (PBPK) modeling to simulate the systemic exposures of CP-I among cancer populations receiving either our model-informed 500 mg or clinically approved 1000 mg abiraterone acetate (AA) dosage. Simulated data were compared with clinical CP-I concentrations determined among our nine metastatic prostate cancer patients receiving 500 mg AA treatment. Abiraterone inhibited OATP1B3-mediated, but not OATP1B1-mediated, uptake of CP-I in vitro, with an estimated K_i of 3.93 μM. Baseline CP-I concentrations were simulated to be 0.81 ± 0.26 ng/ml and determined to be 0.72 ± 0.16 ng/ml among metastatic prostate cancer patients, both of which were higher than those observed for healthy subjects. PBPK simulations revealed an absence of OATP1B3-mediated interaction between abiraterone and CP-I. Our clinical observations confirmed that CP-I concentrations remained comparable to baseline levels up to 12 weeks post 500 mg AA treatment. Using CP-I as an endogenous biomarker, we identified the inhibition of abiraterone on OATP1B3 but not OATP1B1 in vitro, which was predicted and observed to be clinically insignificant. We concluded that the interaction risk between AA and substrates of OATP1Bs is low.

Antifolates are important for chemotherapy in non–small cell lung cancer (NSCLC). They mainly rely on reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT) to enter cells. PCFT is supposed to be the dominant transporter of the two in tumors, as it operates optimally at acidic pH and has limited transport activity at physiological pH, whereas RFC operates optimally at neutral pH. In this study, we found RFC showed a slightly pH-dependent uptake of antifolates, with similar affinity values at pH 7.4 and 6.5. PCFT showed a highly pH-dependent uptake of antifolates, with an optimum pH of 6.0 for pemetrexed and 5.5 for methotrexate. The Michaelis-Menten constant (K_m) value of PCFT for pemetrexed at pH 7.4 was more than 10 times higher than that at pH 6.5. Interestingly, we found that antifolate accumulations mediated by PCFT at acidic pH were significantly affected by the efflux transporter, breast cancer resistance protein (BCRP). The highest pemetrexed concentration was observed at pH 7.0–7.4 after a 60-minute accumulation in PCFT-expressing cells, which was further evidenced by the cytotoxicity of pemetrexed, with the IC₅₀ value of pemetrexed at pH 7.4 being one-third of that at pH 6.5. In addition, the in vivo study indicated that increasing PCFT and RFC expression significantly enhanced the antitumor efficacy of pemetrexed despite the high expression of BCRP. These results suggest that both RFC and PCFT are important for antifolates accumulation in NSCLC, although there is an acidic microenvironment and high BCRP expression in tumors.

A STING (stimulator of interferon genes) agonist GSK3996915 under investigation in early discovery for hepatitis B was orally dosed to a mouse model for understanding the parent drug distribution in liver, the target organ. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) was used to quantify the distribution of GSK3996915 in liver collected from mice administered a single oral dose at 90 mg/kg. GSK3996915 was detected with a zonal distribution localized in the portal triad and highly concentrated in the main bile ducts, indicating clearance through biliary excretion. High spatial resolution imaging showed the distribution of the parent drug localized to the cellular populations in the sinusoids, including the Kupffer cells. Additionally, a series of drug-related metabolites were observed to be localized in the central zones of the liver. These results exemplify the potential of utilizing MALDI IMS for measuring not only quantitative drug distribution and target exposure but also drug metabolism and elimination in a single suite of experiments.