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In the lead-up to the Truth Matters conference in October, we will be focusing our attention on the sufficiency, authority, and clarity of Scripture. One of our previous blog series, Looking for Truth in All the Wrong Places, strongly emphasizes those doctrines. The following entry from that series originally appeared on June 5, 2017. -ed.

God told me.

The Holy Spirit laid it on my heart.

The Spirit is compelling me.

Those phrases and others like them are frequently thrown around the church today without giving many people pause. In fact, it seems the Holy Spirit’s primary role is laying burdens on believers and compelling them to deliver specific, timely messages to the church.

But how do we know when it’s actually the Holy Spirit, and not just a heavy conscience, a strong personal desire, or emotion-driven enthusiasm? For that matter, what’s to say it wasn’t simply some bad pizza? For all the talk about the Holy Spirit directing us, speaking to us and through us, and compelling us this way and that, how do we know when God is truly leading us?

We recently asked John MacArthur about how we can discern the Spirit’s ongoing work in the lives of believers. Here’s what he said:

We ought to look for the Holy Spirit’s leadership, but we must be cautious about assigning to Him responsibility for our words and actions. Our feelings are not necessarily a trustworthy source of information, nor are they an accurate indication that God has a special message to deliver to us or through us.

God’s people need to be circumspect when it comes to His leadership, particularly through subjective impressions and inclinations. Moreover, we need to be wary of those who highjack the prophetic seat and presume to speak for God.

In the days ahead, we’re going to look at some landmark teaching from John MacArthur regarding the propensity of many believers to look for eternal truth in all the wrong places. You won’t want to miss this engaging, insightful series that deals with the pitfalls of subjectivity and postmodernity, and the sufficiency of Scripture.

In the lead-up to the Truth Matters conference in October, we will be focusing our attention on the sufficiency, authority, and clarity of Scripture. One of our previous blog series, Looking for Truth in All the Wrong Places, strongly emphasizes those doctrines. The following entry from that series originally appeared on June 28, 2017. -ed.

From the very beginning, the battle between good and evil has been a battle for the truth. The serpent, in the Garden of Eden, began his temptation by questioning the truthfulness of God’s previous instruction:

Now the serpent was more crafty than any beast of the field which the Lord God had made. And he said to the woman, “Indeed, has God said, ‘You shall not eat from any tree of the garden’?” . . . The serpent said to the woman, “You surely will not die! For God knows that in the day you eat from it your eyes will be opened, and you will be like God, knowing good and evil.” (Genesis 3:1, 4–5)

Casting doubt on the straightforward revelation of God has been Satan’s tactic ever since (cf. John 8:44; 2 Corinthians 11:44).

With eternity at stake, it is no wonder that Scripture reserves its harshest words of condemnation for those who would put lies in the mouth of God, usurping His Word with dangerous experience that is paltry in comparison. The serpent was immediately cursed in the Garden of Eden (Genesis 3:14), and Satan told of his inevitable demise (v. 15). In Old Testament Israel, false prophecy was a capital offense (Deuteronomy 13:5, 10), a point vividly illustrated by Elijah’s slaughter of the four hundred and fifty prophets of Baal following the showdown on Mount Carmel (1 Kings 18:19, 40).

But the Israelites often failed to expel false prophets; and by welcoming error into their midst, they also invited God’s judgment (Jeremiah 5:29–31). Consider the Lord’s attitude toward those who would exchange His true Word for a counterfeit:

Then the Lord said to me, “The prophets are prophesying falsehood in My name. I have neither sent them nor commanded them nor spoken to them; they are prophesying to you a false vision, divination, futility and the deception of their own minds. Therefore thus says the Lord concerning the prophets who are prophesying in My name, although it was not I who sent them—yet they keep saying, ‘There will be no sword or famine in this land’—by sword and famine those prophets shall meet their end! The people also to whom they are prophesying will be thrown out into the streets of Jerusalem because of the famine and the sword; and there will be no one to bury them—neither them, nor their wives, nor their sons, nor their daughters—for I will pour out their own wickedness on them.” (Jeremiah 14:14-16; cf. Isaiah 30:9-13; Ezekiel 13:3-9)

The point of those passages is unmistakable: God hates those who misrepresent His Word or speak lies in His name. The New Testament responds to false prophets with equal severity (cf. 1 Timothy 6:3–5; 2 Timothy 3:1–9; 1 John 4:1–3; 2 John 7–11). God does not tolerate those who falsify or fake divine revelation. It is an offense He takes personally, and His retribution is swift and deadly. To sabotage biblical truth in any way—by adding to it, subtracting from it, or mixing it with error—is to invite divine wrath (Galatians 1:9; 2 John 9–11). Any distortion of the Word is an affront against the Trinity, and especially against the Spirit of God because of His intimate relationship to the Scriptures.

Martin Luther put it this way, “Whenever you hear anyone boast that he has something by inspiration of the Holy Spirit and it has no basis in God’s Word, no matter what it may be, tell him that this is the work of the devil.” ^[1]Martin Luther, Luther’s Works, Vol. 23, ed. Jaroslav Pelikan (St. Louis: Concordia: 1959), 173–174. And elsewhere, “Whatever does not have its origin in the Scriptures is surely from the devil himself.” ^[2]Luther’s Works, Vol. 36, 144.

Although charismatics claim to represent the Holy Spirit, their movement has shown a persistent tendency to pit Him against the Scriptures—as if a commitment to biblical truth somehow might quench, grieve, or otherwise inhibit the Spirit’s ministry. But nothing could be further from the truth. The Bible is the Holy Spirit’s book! It is the instrument He uses to convict unbelievers of sin, righteousness, and judgment. It is the sword by which He energizes the proclamation of the gospel, piercing the hearts of the spiritually dead and raising them to spiritual life. It is the means by which He unleashes His sanctifying power in the lives of those who believe—growing them in grace through the pure milk of biblical instruction.

Thus, to reject the Scriptures is to rebuff the Spirit. To ignore, disdain, twist, or disobey the Word of God is to dishonor the One who inspired, illumines, and empowers it. But to wholeheartedly embrace and submit to biblical truth is to enjoy the fullness of the Spirit’s ministry—being filled by His sanctifying power, being led by Him in righteousness, and being equipped with His armor in the battle against sin and error.

Charles Spurgeon explained it this way to his congregation:

We have a more sure word of testimony, a rock of truth upon which we rest, for our infallible standard lies in, “It is written. . .” The Bible, the whole Bible, and nothing but the Bible, is our religion. . . . It is said that it is hard to understand, but it is not so to those who seek the guidance of the Spirit of God. . . .  A babe in grace taught by the Spirit of God may know the mind of the Lord concerning salvation, and find its way to heaven by the guidance of the Word alone. But be it profound or simple; that is not the question; it is the Word of God, and is pure, unerring truth. Here is infallibility, and nowhere else. . . . This grand, infallible book . . . is our sole court of appeal. . . . [It is] the sword of the Spirit in the spiritual conflicts which await. . . . The Holy Spirit is in the Word, and it is, therefore, living truth. O Christians, be ye sure of this, and because of it make you the word your chosen weapon of war. ^[3]Charles Spurgeon, “Infallibility—Where to Find It and How to Use It,” The Metropolitan Tabernacle Pulpit, Vol. 20 (London: Passmore & Alabaster, 1874), 698-99, 702.

The Bible is a living book because the living Spirit of God energizes and empowers it. The Word convicts us, instructs us, equips us, strengthens us, protects us, and enables us to grow. Or more accurately, the Holy Spirit does all of those things as He activates the truth of Scripture in our hearts.

As believers, we honor the Spirit most when we honor the Scriptures—studying them diligently, applying them carefully, arming our minds with their precepts, and embracing their teaching with all of our hearts. The Spirit has given us the Word. He has opened our eyes to understand its vast riches. And He empowers its truth in our lives as He conforms us into the image our Savior.

It is difficult to imagine why anyone would ever disdain or neglect the words of this Book, especially in light of the divinely promised blessings that come from cherishing it. As the psalmist declared so long ago:

How blessed is the man who does not walk in the counsel of the wicked, nor stand in the path of sinners, nor sit in the seat of scoffers! But his delight is in the law of the Lord, and in His law he meditates day and night. He will be like a tree firmly planted by streams of water, which yields its fruit in its season and its leaf does not wither; and in whatever he does, he prospers. (Psalm 1:1-3)

(Adapted from Strange Fire.)

People don’t always do the things they know they should. Whether it’s eating vegetables, paying bills promptly, or getting to bed on time, some people’s everyday actions defy what they know to be best. That’s often the same for believers with our Bibles. God’s people may recognize the importance of feeding on God’s Word even while we allow it to gather dust on the shelf.

That’s why the apostle Peter exhorts his readers: “Therefore, putting aside all malice and deceit and hypocrisy and envy and all slander, like newborn babies, long for the pure milk of the word” (1 Peter 2:1–2).   

First Peter 2:1 begins with the word “Therefore,” linking the Apostle’s exhortation to the foundational reality that should fuel our hunger for God’s Word—Peter’s prior statements, specifically, verses 23–25 of chapter 1, where he writes,

You have been born again not of seed which is perishable but imperishable, that is, through the living and enduring word of God. For, “All flesh is like grass, and all its glory like the flower of grass. The grass withers, and the flower falls off, but the word of the Lord endures forever.” And this is the word which was preached to you. (1 Peter 1:23–25)

Peter wants us to understand that it was the incorruptible, imperishable Word of God that has saved us and transform us into new creations.

To grasp the full weight of what Peter is saying, we need to remember our spiritual destitution prior to regeneration. We possessed unrepentant hearts that were “more deceitful than all else and . . . desperately sick; who can understand it?” (Jeremiah 17:9). In Romans 3, Paul uses quotes from the Old Testament to describe how comprehensive our depravity was: “There is none righteous, not even one; there is none who understands, there is none who seeks for God; all have turned aside, together they have become useless; there is none who does good, there is not even one” (Romans 3:10–12). He sums up the corruption of that rebellious state: “There is no fear of God before their eyes” (Romans 3:18). Not only were we incapable of escaping our depravity, we were unwilling to do so. Before the Spirit did His illuminating work through the Word, we had no fear of the Lord or of the due penalty of our sins.

From that horrendous state, Peter says we “have been born again not of seed which is perishable but imperishable, that is, through the living and enduring word of God” (1 Peter 1:23). Peter identifies this Word as the source of our spiritual transformation. Borrowing a metaphor from the life of Christ, Peter describes the Word as an imperishable seed. Just as Jesus explained to His disciples in Matthew 13, a faithful sower cast seed onto soil prepared by the Spirit, and the seed bore fruit (Matthew 13:3–23). Describing the Bible’s transforming power, James says, “In the exercise of His will He brought us forth by the word of truth, so that we would be a kind of first fruits among His creatures” (James 1:18). Referring to the saving work of the Word, John writes in his gospel, “These have been written so that you may believe that Jesus is the Christ, the Son of God; and that believing you may have life in His name” (John 20:31). And in response to all that Scripture has already accomplished in our lives, Peter charges us to cultivate a hunger for it.

Why? Because the power of God’s Word does not fade, diminish, or wither (1 Peter 1:24). It is the source of both our transformation and our sanctification. It is our spiritual sustenance (Matthew 4:4). It gives us stability and security: “Therefore everyone who hears these words of Mine and acts on them, may be compared to a wise man who built his house on the rock” (Matthew 7:24). Scripture is “the word of [God’s] grace, which is able to build you up and to give you the inheritance among all those who are sanctified” (Acts 20:32). It is “the word of life” (Philippians 2:16). Regarding its power, the writer of Hebrews says, “The word of God is living and active and sharper than any two-edged sword, and piercing as far as the division of soul and spirit, of both joints and marrow, and able to judge the thoughts and intentions of the heart” (Hebrews 4:12). God’s living Word, active and powerful, saves, sustains, and sanctifies His people.

Believers recognize the Word for what it is and for what it does in their lives. Writing to the Thessalonians, Paul said, “For this reason we also constantly thank God that when you received the word of God which you heard from us, you accepted it not as the word of men, but for what it really is, the word of God, which also performs its work in you who believe” (1 Thessalonians 2:13). Scripture was instrumental in our salvation, and it continues to perform God’s work in us. Moreover, we know it accomplishes God’s work without fail.

For as the rain and the snow come down from heaven, and do not return there without watering the earth and making it bear and sprout, and furnishing seed to the sower and bread to the eater; so will My word be which goes forth from My mouth; it will not return to Me empty, without accomplishing what I desire, and without succeeding in the matter for which I sent it. (Isaiah 55:10–11)

If we want to experience God’s supernatural work in our lives, we must understand that the Holy Spirit accomplishes it only through His Word. He has ordained no other means, no momentary emotional or existential experience that can catapult us to some greater spiritual maturity. We cannot set aside our Bibles and expect His sanctifying work to continue uninterrupted. God saved us through the power of His Word, and its work is not finished. We must increase our hunger for His truth, knowing it is the sole source of our spiritual lives and the only means by which the Spirit conforms us into the image of His Son.

(Adapted from Final Word)

Every form of unbelief is just another version of idolatry. Even atheists refute themselves by voicing hatred for the God they deny. Creation is proof of a Creator, but those who do not acknowledge the God of the Bible often imagine it was the work of some nebulous, distant, and uncaring superpower.

Manssour Bin Mussallam, is Secretary General-elect of the Organisation of Educational Cooperation (OEC)

The post The COVID-19 Pandemic and the Reinvention of the Spirit of Solidarity and Cooperation appeared first on Inter Press Service.

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BERLIN: The world must draw lessons from the past and work together to beat the coronavirus pandemic, European leaders urged as the continent marked 75 years since the end of World War II in Europe. With parades and commemoration events cancelled or scaled down to contain the outbreak, Europe and...

FRANKFURT AM MAIN: An Indian national will stand trial in Germany accused of spying on Sikh and Kashmiri communities for New Delhi’s secret service, a court said on Friday.Federal prosecutors allege the suspect, identified as 54-year-old Balvir, has been working with the Indian foreign...

Global leaders marked 75 years since the end of World War II in Europe Friday, urging citizens to draw inspiration from the historic victory as the world battles against the coronavirus pandemic.

FRANKFURT: An Indian national will stand trial in Germany accused of spying on Sikh and Kashmiri communities for New Delhi’s spy agency, a court said on Friday.Federal prosecutors allege the suspect, identified as 54-year-old Balvir, has been working with the Indian foreign intelligence...

Two people were wounded in two separate firing incidents on Friday. A 40-year-old man, Feroz, son of Salman, was injured near Mauripur’s Gate No. 15. The man was taken to the Civil Hospital for medical attention.The Jackson police said that the incident took place when a traffic police cop...

Microchip Solves Interoperability Challenges of Delivering up to 90 Watts of Power Over Ethernet Wiring

Former Prime Minister Saad Hariri Thursday dismissed as not useful the meeting held the previous day at Baabda Palace to discuss the economic financial rescue plan which he and his parliamentary Future bloc boycotted.

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A London bus stop has been transformed into a children's art gallery by a local resident who wanted to brighten the drudgery of lockdown life, creating a colourful community hub amid the anxiety and isolation of the COVID-19 pandemic.

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ABSTRACT

Coinfections shape immunity and influence the development of inflammatory diseases, resulting in detrimental or beneficial outcome. Coinfections with concurrent Plasmodium species can alter malaria clinical evolution, and malaria infection itself can modulate autoimmune reactions. Yet, the underlying mechanisms remain ill defined. Here, we demonstrate that the protective effects of some rodent malaria strains on T cell-mediated inflammatory pathologies are due to an RNA virus cohosted in malaria-parasitized blood. We show that live and extracts of blood parasitized by Plasmodium berghei K173 or Plasmodium yoelii 17X YM, protect against P. berghei ANKA-induced experimental cerebral malaria (ECM) and myelin oligodendrocyte glycoprotein (MOG)/complete Freund’s adjuvant (CFA)-induced experimental autoimmune encephalomyelitis (EAE), and that protection is associated with a strong type I interferon (IFN-I) signature. We detected the presence of the RNA virus lactate dehydrogenase-elevating virus (LDV) in the protective Plasmodium stabilates and we established that LDV infection alone was necessary and sufficient to recapitulate the protective effects on ECM and EAE. In ECM, protection resulted from an IFN-I-mediated reduction in the abundance of splenic conventional dendritic cell and impairment of their ability to produce interleukin (IL)-12p70, leading to a decrease in pathogenic CD4⁺ Th1 responses. In EAE, LDV infection induced IFN-I-mediated abrogation of IL-23, thereby preventing the differentiation of granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing encephalitogenic CD4⁺ T cells. Our work identifies a virus cohosted in several Plasmodium stabilates across the community and deciphers its major consequences on the host immune system. More generally, our data emphasize the importance of considering contemporaneous infections for the understanding of malaria-associated and autoimmune diseases.

IMPORTANCE Any infection modifies the host immune status, potentially ameliorating or aggravating the pathophysiology of a simultaneous inflammatory condition. In the course of investigating how malaria infection modulates the severity of contemporaneous inflammatory diseases, we identified a nonpathogenic mouse virus in stabilates of two widely used rodent parasite lines: Plasmodium berghei K173 and Plasmodium yoelii 17X YM. We established that the protective effects of these Plasmodium lines on cerebral malaria and multiple sclerosis are exclusively due to this virus. The virus induces a massive type I interferon (IFN-I) response and causes quantitative and qualitative defects in the ability of dendritic cells to promote pathogenic T cell responses. Beyond revealing a possible confounding factor in rodent malaria models, our work uncovers some bases by which a seemingly innocuous viral (co)infection profoundly changes the immunopathophysiology of inflammatory diseases.

To the Editor—Bourbon virus (Thogotovirus, Orthomyxoviridae) was discovered in 2014 when a patient with history of multiple tick bites in Kansas died from an unknown infection [1]. Human infections from Bourbon virus have now been recognized in several states (i.e., Kansas, Oklahoma, Missouri). The virus was detected in collections of the lone star tick (Amblyomma americanum) in Missouri [2]. A serosurvey of domestic and wild mammals in Missouri noted the presence of Bourbon virus-neutralizing antibodies in serum samples collected from a variety of species, but most frequently in white-tailed deer (Odocoileus virginianus) and raccoon (Procyon lotor) [3]. We report here that neutralizing antibodies against Bourbon virus were detected in white-tailed deer in North Carolina, suggesting that the virus is present in the state. We screened 32 white-tailed deer for the presence of Bourbon virus-specific neutralizing antibodies. Of 20 plasma samples that reacted with the virus, 18 were confirmed with neutralizing antibody titers ranging from 10 to ≥ 320 for a seroprevalence rate of 56% (95% confidence interval 39%–72%). The seropositive samples were from deer killed during the 2014 hunting season from Stanly and New Hanover counties.

The incidence of Bourbon virus infection in humans in North Carolina is unknown. However, given the abundance of the lone star tick in the state, and the notable proportion of deer with evidence of infection, human infections have likely gone unnoticed or possibly misdiagnosed. Human infection with Bourbon virus results in a nonspecific viral syndrome that includes fever, nausea, diarrhea, myalgia (muscle pain), arthralgia...

A novel lytic bacteriophage, ValSw3-3, which efficiently infects pathogenic strains of Vibrio alginolyticus, was isolated from sewage water and characterized by microbiological and in silico genomic analyses. Transmission electron microscopy indicated that ValSw3-3 has the morphology of siphoviruses. This phage can infect four species in the Vibrio genus and has a latent period of 15 min and a burst size of 95 ± 2 PFU/infected bacterium. Genome sequencing results show that ValSw3-3 has a 39,846-bp double-stranded DNA genome with a GC content of 43.1%. The similarity between the genome sequences of ValSw3-3 and those of other phages recorded in the GenBank database was below 50% (42%), suggesting that ValSw3-3 significantly differs from previously reported phages at the DNA level. Multiple genome comparisons and phylogenetic analysis based on the major capsid protein revealed that phage ValSw3-3 is grouped in a clade with five other phages, including Listonella phage phiHSIC (GenBank accession no. NC_006953.1), Vibrio phage P23 (MK097141.1), Vibrio phage pYD8-B (NC_021561.1), Vibrio phage 2E1 (KX507045.1), and Vibrio phage 12G5 (HQ632860.1), and is distinct from all known genera within the Siphoviridae family that have been ratified by the International Committee on Taxonomy of Viruses (ICTV). An in silico proteomic comparison of diverse phages from the Siphoviridae family supported this clustering result and suggested that ValSw3-3, phiHSIC, P23, pYD8-B, 2E1, and 12G5 should be classified as a novel genus cluster of Siphoviridae. A subsequent analysis of core genes also revealed the common genes shared within this new cluster. Overall, these results provide a characterization of Vibrio phage ValSw3-3 and support our proposal of a new viral genus within the family Siphoviridae.

IMPORTANCE Phage therapy has been considered a potential alternative to antibiotic therapy in treating bacterial infections. For controlling the vibriosis-causing pathogen Vibrio alginolyticus, well-documented phage candidates are still lacking. Here, we characterize a novel lytic Vibrio phage, ValSw3-3, based on its morphology, host range and infectivity, growth characteristics, stability under various conditions, and genomic features. Our results show that ValSw3-3 could be a potent candidate for phage therapy to treat V. alginolyticus infections due to its stronger infectivity and better pH and thermal stability than those of previously reported Vibrio phages. Moreover, genome sequence alignments, phylogenetic analysis, in silico proteomic comparison, and core gene analysis all support that this novel phage, ValSw3-3, and five unclassified phages form a clade distant from those of other known genera ratified by the ICTV. Thus, we propose a new viral genus within the Siphoviridae family to accommodate this clade, with ValSw3-3 as a representative member.

The Dukla Nappe in the Skrzydlna area exposes two types of mélange reflecting two different phases of basinal and tectonic evolution of the Outer West Carpathian orogen in its Polish sector. The Oligocene-age sedimentary mélange (olistostrome) is related to growth of the accretionary wedge, whereas the Miocene-age diapiric mélange postdates the orogenic thrusting. Textural and structural features of the very coarse-grained sedimentary mélange suggest non-cohesive debris flows and high-density turbidity currents as predominant emplacement mechanisms. Growth strata, associated with progressive unconformities, and facies contrast between the underlying fine-grained unit and the overlying olistostrome reflect a considerable uplift of the source area and rotation of the adjacent part of the basin floor. The olistostrome and the overlying turbidite succession form a retrogressive sequence interpreted as a submarine canyon infill grading to a small submarine fan. The diapiric mélange, injected into the Oligocene-age succession of the Dukla Nappe, contains the Early and Late Cretaceous-age blocks and matrix derived from the underlying Silesian Nappe. The features reflecting diapiric emplacement include matrix proportion increase and block content decrease towards the mélange margins, scaly fabric and shear zones. Both mélanges, interpreted in the past as chaotic bodies, upon detailed examination reveal genesis-related subtle internal organization.

A significant part of mélanges recognized in exhumed convergent margins around the world has been recently documented to have chiefly originated from masse transport and subsurface remobilization and disruption (i.e. mélanges, from sedimentary and mud–serpentinite diapiric processes and from in situ fluidification–disruption). Tectonic and/or sedimentary processes occurring during subsequent multiple deformational events of convergent margin evolution commonly overprint and significantly rework the primary (sedimentary or diapiric) mélange fabric, forming polygenetic mélanges. This ultimately complicates their distinction from true tectonic mélanges, masking part of the recorded tectono-sedimentary evolution of the associated convergent margin. The contributions gathered in this thematic collection explore with different approaches (from field structural and stratigraphic observations to geophysical analyses) different types of polygenetic mélange, at various scales, around the world. These studies conclude that the understanding of this type of mélange may provide crucial insights for a more detailed interpretation of the evolution of ancient and modern convergent margins, and of processes and mechanisms triggering potential natural hazards (earthquakes and tsunamis). Case studies include the Apennines in the Central Mediterranean region, the Carpathians in Central Europe and the Nankai Prism in Japan.

Thematic collection: This article is part of the ‘Polygenetic mélanges: a glimpse on tectonic sedimentary and diapiric recycling in convergent margins’ collection available at https://www.lyellcollection.org/cc/polygenetic-melanges

The need to characterize and distinguish geographically adjacent aggregate quarry sources prompted the SEM-EDS analysis of pyrite (FeS₂) within fill material taken from eight different quarry sources. This experiment was undertaken to investigate the possibility of geochemically separating these quarry sources based on the major element concentration of their pyrite. The results show that median values for Fe and S vary by up to 7.6 and 8.55 wt% respectively. By implementing statistical methods, including k-means clustering and principal component analysis, it is possible to geochemically discriminate three of the eight sources.

Transcription of a chromatin template involves the concerted interaction of many different proteins and protein complexes. Analyses of specific factors showed that these interactions change during stress and upon developmental switches. However, how the binding of multiple factors at any given locus is coordinated has been technically challenging to investigate. Here we used Epi-Decoder in yeast to systematically decode, at one transcribed locus, the chromatin binding changes of hundreds of proteins in parallel upon perturbation of transcription. By taking advantage of improved Epi-Decoder libraries, we observed broad rewiring of local chromatin proteomes following chemical inhibition of RNA polymerase. Rapid reduction of RNA polymerase II binding was accompanied by reduced binding of many other core transcription proteins and gain of chromatin remodelers. In quiescent cells, where strong transcriptional repression is induced by physiological signals, eviction of the core transcriptional machinery was accompanied by the appearance of quiescent cell–specific repressors and rewiring of the interactions of protein-folding factors and metabolic enzymes. These results show that Epi-Decoder provides a powerful strategy for capturing the temporal binding dynamics of multiple chromatin proteins under varying conditions and cell states. The systematic and comprehensive delineation of dynamic local chromatin proteomes will greatly aid in uncovering protein–protein relationships and protein functions at the chromatin template.

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung condition, causing progressive decline in lung function leading to premature death. Acute exacerbations in COPD patients are predominantly associated with respiratory viruses. Ribavirin is a generic broad-spectrum antiviral agent that could be used for treatment of viral respiratory infections in COPD. Using the Particle Replication In Nonwetting Templates (PRINT) technology, which produces dry-powder particles of uniform shape and size, two new inhaled formulations of ribavirin (ribavirin-PRINT-CFI and ribavirin-PRINT-IP) were developed for efficient delivery to the lung and to minimize bystander exposure. Ribavirin-PRINT-CFI was well tolerated in healthy participants after single dosing and ribavirin-PRINT-IP was well tolerated in healthy and COPD participants after single and repeat dosing. Ribavirin-PRINT-CFI was replaced with ribavirin-PRINT-IP since the latter formulation was found to have improved physicochemical properties and it had a higher ratio of active drug to excipient per unit dose. Ribavirin concentrations were measured in lung epithelial lining fluid in both healthy and COPD participants and achieved target concentrations. Both formulations were rapidly absorbed with approximately dose proportional pharmacokinetics in plasma. Exposure to bystanders was negligible based on both the plasma and airborne ribavirin concentrations with the ribavirin-PRINT-IP formulation. Thus, ribavirin-PRINT-IP allowed for an efficient and convenient delivery of ribavirin to the lungs while minimizing systemic exposure. Further clinical investigations would be required to demonstrate ribavirin-PRINT-IP antiviral characteristics and impact on COPD viral-induced exacerbations. (The clinical trials discussed in this study have been registered at ClinicalTrials.gov under identifiers NCT03243760 and NCT03235726.)

Etravirine (ETR) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) used in treatment-experienced individuals. Genotypic resistance test-interpretation systems can predict ETR resistance; however, genotype-based algorithms are derived primarily from HIV-1 subtype B and may not accurately predict resistance in non-B subtypes. The frequency of ETR resistance among recombinant subtype C HIV-1 and the accuracy of genotypic interpretation systems were investigated. HIV-1_LAI containing full-length RT from HIV-1 subtype C-positive individuals experiencing virologic failure (>10,000 copies/ml and >1 NNRTI resistance-associated mutation) were phenotyped for ETR susceptibility. Fold change (FC) was calculated against a composite 50% effective concentration (EC₅₀) from treatment-naive individuals and three classifications were assigned: (i) <2.9-FC, susceptible; (ii) ≥2.9- to 10-FC, partially resistant; and (iii) >10-FC, fully resistant. The Stanford HIVdb-v8.4 was used for genotype predictions merging the susceptible/potential low-level and low-level/intermediate groups for 3 x 3 comparison. Fifty-four of a hundred samples had reduced ETR susceptibility (≥2.9-FC). The FC correlated with HIVdb-v8.4 (Spearman’s rho = 0.62; P < 0.0001); however, 44% of samples were partially (1 resistance classification difference) and 4% completely discordant (2 resistance classification differences). Of the 34 samples with an FC of >10, 26 were HIVdb-v8.4 classified as low-intermediate resistant. Mutations L100I, Y181C, or M230L were present in 27/34 (79%) of samples with an FC of >10 but only in 2/46 (4%) of samples with an FC of <2.9. No other mutations were associated with ETR resistance. Viruses containing the mutation K65R were associated with reduced ETR susceptibility, but 65R reversions did not increase ETR susceptibility. Therefore, genotypic interpretation systems were found to misclassify ETR susceptibility in HIV-1 subtype C samples. Modifications to genotypic algorithms are needed to improve the prediction of ETR resistance for the HIV-1 subtype C.

If you're 13 to 24 years old and love to make movies, you'll want to enter the Windsor Youth Short Film Showcase next week. Organizer Gemma Eva says the project is meant to spotlight local "Gen-Z filmmakers."

Job postings from a NASA contractor suggest that a new humanoid robot is under development

The fastest, safest, and most exciting way to launch a quadrotor may be ballistically

Destiny 2 Trials of Osiris returns once again later today – here's what you need to know for this week's end-game PvP challenge.

Whether it’s printed and high-necked or floral and ruffled, brighten your lockdown by dressing up to stay in