noc

IRAK-M Regulates Monocyte Trafficking to the Lungs in Response to Bleomycin Challenge [IMMUNE REGULATION]

Key Points

  • TLR signaling pathway regulates expression of monocyte chemoattractant CCR2.

  • IRAK-M is an important regulator of monocyte trafficking to the lung in fibrosis.




    noc

    Development of an Extended-Specificity Multiplex Immunoassay for Detection of Streptococcus pneumoniae Serotype-Specific Antigen in Urine by Use of Human Monoclonal Antibodies [Diagnostic Laboratory Immunology]

    Current pneumococcal vaccines cover the 10 to 23 most common serotypes of the 92 presently described. However, with the increased usage of pneumococcal-serotype-based vaccines, the risk of serotype replacement and an increase in disease caused by nonvaccine serotypes remains. Serotype surveillance of pneumococcal infections relies heavily on culture techniques, which are known to be insensitive, particularly in cases of noninvasive disease. Pneumococcal-serotype-specific urine assays offer an alternative method of serotyping for both invasive and noninvasive disease. However, the assays described previously cover mainly conjugate vaccine serotypes, give little information about circulating nonvaccine serotypes, and are currently available only in one or two specialist laboratories. Our laboratory has developed a Luminex-based extended-range antigen capture assay to detect pneumococcal-serotype-specific antigens in urine samples. The assay targets 24 distinct serotypes/serogroups plus the cell wall polysaccharide (CWP) and some cross-reactive serotypes. We report that the assay is capable of detecting all the targeted serotypes and the CWP at 0.1 ng/ml, while some serotypes are detected at concentrations as low as 0.3 pg/ml. The analytical serotype specificity was determined to be 98.4% using a panel of polysaccharide-negative urine specimens spiked with nonpneumococcal bacterial antigens. We also report clinical sensitivities of 96.2% and specificities of 89.9% established using a panel of urine specimens from patients diagnosed with community-acquired pneumonia or pneumococcal disease. This assay can be extended for testing other clinical samples and has the potential to greatly improve serotype-specific surveillance in the many cases of pneumococcal disease in which a culture is never obtained.




    noc

    Monoclonal antibody treatment during pregnancy and/or lactation in women with MS or neuromyelitis optica spectrum disorder

    Objective

    To assess possible adverse effects on breastfed infants of mothers receiving monoclonal antibodies (MAbs) during pregnancy and/or lactation.

    Methods

    We identified 23 patients from the German Multiple Sclerosis and Pregnancy Registry (DMSKW) who received MAbs (17 natalizumab and 6 anti-CD20) during lactation. Thirteen were already exposed to natalizumab during the third trimester of pregnancy, and 1 received ocrelizumab during pregnancy. Data were obtained from standardized, telephone-administered questionnaires completed by the mother during pregnancy and at 1, 3, 6, and 12 months postpartum. Natalizumab concentration in mother’s milk was analyzed in 3 patients and natalizumab serum concentration in 2 of these patients and their breastfed infants.

    Results

    We did not observe a negative impact on infant health and development attributable to breast milk exposure after a median follow-up of 1 year. Infants exposed to natalizumab during the third trimester had a lower birth weight and more hospitalizations in the first year of life. The concentration of natalizumab in breast milk and serum of infants was low; B cells normal in infants breastfed under anti-CD20.

    Conclusion

    More data on the effect of Mab exposure during pregnancy are needed. Otherwise, our data suggest that treatment with natalizumab, ocrelizumab, or rituximab during lactation might be safe for breastfed infants.




    noc

    Monocarboxylate Transporters (SLC16): Function, Regulation, and Role in Health and Disease [Review Articles]

    The solute carrier family 16 (SLC16) is comprised of 14 members of the monocarboxylate transporter (MCT) family that play an essential role in the transport of important cell nutrients and for cellular metabolism and pH regulation. MCTs 1–4 have been extensively studied and are involved in the proton-dependent transport of L-lactate, pyruvate, short-chain fatty acids, and monocarboxylate drugs in a wide variety of tissues. MCTs 1 and 4 are overexpressed in a number of cancers, and current investigations have focused on transporter inhibition as a novel therapeutic strategy in cancers. MCT1 has also been used in strategies aimed at enhancing drug absorption due to its high expression in the intestine. Other MCT isoforms are less well characterized, but ongoing studies indicate that MCT6 transports xenobiotics such as bumetanide, nateglinide, and probenecid, whereas MCT7 has been characterized as a transporter of ketone bodies. MCT8 and MCT10 transport thyroid hormones, and recently, MCT9 has been characterized as a carnitine efflux transporter and MCT12 as a creatine transporter. Expressed at the blood brain barrier, MCT8 mutations have been associated with an X-linked intellectual disability, known as Allan-Herndon-Dudley syndrome. Many MCT isoforms are associated with hormone, lipid, and glucose homeostasis, and recent research has focused on their potential roles in disease, with MCTs representing promising novel therapeutic targets. This review will provide a summary of the current literature focusing on the characterization, function, and regulation of the MCT family isoforms and on their roles in drug disposition and in health and disease.

    Significance Statement

    The 14-member solute carrier family 16 of monocarboxylate transporters (MCTs) plays a fundamental role in maintaining intracellular concentrations of a broad range of important endogenous molecules in health and disease. MCTs 1, 2, and 4 (L-lactate transporters) are overexpressed in cancers and represent a novel therapeutic target in cancer. Recent studies have highlighted the importance of MCTs in glucose, lipid, and hormone homeostasis, including MCT8 in thyroid hormone brain uptake, MCT12 in carnitine transport, and MCT11 in type 2 diabetes.




    noc

    Ivacaftor decreases monocyte sensitivity to interferon-{gamma} in people with cystic fibrosis

    Management of cystic fibrosis has been revolutionised by the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators. These compounds treat the underlying molecular basis of the disease by increasing activity of defective CFTR channels, which improves many clinical parameters and enhances patient quality of life [1]. Next-generation modulators, also known as triple combination therapy, promise to be highly efficacious in up to 90% of patients [2] and will likely dramatically change the landscape of cystic fibrosis disease. Studies examining individuals before and after initiation of CFTR modulators have revealed novel functions of CFTR and shown that CFTR modulators do not reverse all disease manifestations [3–5]. Thus, knowledge of the post-modulator cystic fibrosis disease state is crucial for understanding what continued therapies will be needed for people with cystic fibrosis and what new challenges may arise.




    noc

    Contributions of a LysR Transcriptional Regulator to Listeria monocytogenes Virulence and Identification of Its Regulons [Article]

    The capacity of Listeria monocytogenes to adapt to environmental changes is facilitated by a large number of regulatory proteins encoded by its genome. Among these proteins are the uncharacterized LysR-type transcriptional regulators (LTTRs). LTTRs can work as positive and/or negative transcription regulators at both local and global genetic levels. Previously, our group determined by comparative genome analysis that one member of the LTTRs (NCBI accession no. WP_003734782) was present in pathogenic strains but absent from nonpathogenic strains. The goal of the present study was to assess the importance of this transcription factor in the virulence of L. monocytogenes strain F2365 and to identify its regulons. An L. monocytogenes strain lacking lysR (the F2365lysR strain) displayed significant reductions in cell invasion of and adhesion to Caco-2 cells. In plaque assays, the deletion of lysR resulted in a 42.86% decrease in plaque number and a 13.48% decrease in average plaque size. Furthermore, the deletion of lysR also attenuated the virulence of L. monocytogenes in mice following oral and intraperitoneal inoculation. The analysis of transcriptomics revealed that the transcript levels of 139 genes were upregulated, while 113 genes were downregulated in the F2365lysR strain compared to levels in the wild-type bacteria. lysR-repressed genes included ABC transporters, important for starch and sucrose metabolism as well as glycerolipid metabolism, flagellar assembly, quorum sensing, and glycolysis/gluconeogenesis. Conversely, lysR activated the expression of genes related to fructose and mannose metabolism, cationic antimicrobial peptide (CAMP) resistance, and beta-lactam resistance. These data suggested that lysR contributed to L. monocytogenes virulence by broad impact on multiple pathways of gene expression.

    IMPORTANCE Listeria monocytogenes is the causative agent of listeriosis, an infectious and fatal disease of animals and humans. In this study, we have shown that lysR contributes to Listeria pathogenesis and replication in cell lines. We also highlight the importance of lysR in regulating the transcription of genes involved in different pathways that might be essential for the growth and persistence of L. monocytogenes in the host or under nutrient limitation. Better understanding L. monocytogenes pathogenesis and the role of various virulence factors is necessary for further development of prevention and control strategies.




    noc

    Exceptionally well-preserved Permocalculus cf. tenellus (Pia) (Gymnocodiaceae) from Upper Permian Khuff Formation limestones, Saudi Arabia

    An exceptionally well-preserved specimen of the articulated rhodophyte Permocalculus, compared with P. tenellus sensu Elliott, 1955, is described from fine-grained Upper Permian limestones of the Khuff Formation of Saudi Arabia. Longitudinal medullary and sheaf-like cortical filaments extend through the uniserial series of elongate-globular, concave- and convex-terminating, interlocking segments for which they are interpreted to have functioned in articulation. The filaments tend to splay and branch laterally into the cortex where they terminate at the pores. At the terminal aperture, the filaments extend as bifurcating and possibly trifurcating branches and may serve as the origin of a new segment. Numerous elongate-globular chambers, up to five in each row and intimately involved with the filaments, are developed in the outer medulla and are considered to represent reproductive sporangia. The specimen is considered to have occupied predominantly low-energy, normal to slightly elevated salinity, shallow conditions within the subtidal regime of a lagoon.




    noc

    Appropriation of GPIb{alpha} from platelet-derived extracellular vesicles supports monocyte recruitment in systemic inflammation

    Interactions between platelets, leukocytes and the vessel wall provide alternative pathological routes of thrombo-inflammatory leukocyte recruitment. We found that when platelets were activated by a range of agonists in whole blood, they shed platelet-derived extracellular vesicles which rapidly and preferentially bound to blood monocytes compared to other leukocytes. Platelet-derived extracellular vesicle binding to monocytes was initiated by P-selectin-dependent adhesion and was stabilised by binding of phosphatidylserine. These interactions resulted in the progressive transfer of the platelet adhesion receptor GPIbα to monocytes. GPIbα+-monocytes tethered and rolled on immobilised von Willebrand Factor or were recruited and activated on endothelial cells treated with TGF-β1 to induce the expression of von Willebrand Factor. In both models monocyte adhesion was ablated by a function-blocking antibody against GPIbα. Monocytes could also bind platelet-derived extracellular vesicle in mouse blood in vitro and in vivo. Intratracheal instillations of diesel nanoparticles, to model chronic pulmonary inflammation, induced accumulation of GPIbα on circulating monocytes. In intravital experiments, GPIbα+-monocytes adhered to the microcirculation of the TGF-β1-stimulated cremaster muscle, while in the ApoE–/– model of atherosclerosis, GPIbα+-monocytes adhered to the carotid arteries. In trauma patients, monocytes bore platelet markers within 1 hour of injury, the levels of which correlated with severity of trauma and resulted in monocyte clearance from the circulation. Thus, we have defined a novel thrombo-inflammatory pathway in which platelet-derived extracellular vesicles transfer a platelet adhesion receptor to monocytes, allowing their recruitment in large and small blood vessels, and which is likely to be pathogenic.




    noc

    Effects of Vitamin D Receptor Knockout and Vitamin D Deficiency on Corneal Epithelial Wound Healing and Nerve Density in Diabetic Mice

    Diabetic keratopathy occurs in ~70% of all people with diabetes. This study was designed to examine the effects of vitamin D receptor knockout (VDR–/–) and vitamin D deficiency (VDD) on corneal epithelial wound healing and nerve density in diabetic mice. Diabetes was induced using the low-dose streptozotocin method. Corneal epithelial wounds were created using an Algerbrush, and wound healing was monitored over time. Corneal nerve density was measured in unwounded mice. VDR–/– and VDD diabetic mice (diabetic for 8 and 20 weeks, respectively) had slower healing ratios than wild-type diabetic mice. VDR–/– and VDD diabetic mice also showed significantly decreased nerve density. Reduced wound healing ratios and nerve densities were not fully rescued by a supplemental diet rich in calcium, lactose, and phosphate. We conclude that VDR–/– and VDD significantly reduce both corneal epithelial wound healing and nerve density in diabetic mice. Because the supplemental diet did not rescue wound healing or nerve density, these effects are likely not specifically related to hypocalcemia. This work supports the hypothesis that low vitamin D levels can exacerbate preexisting ophthalmic conditions, such as diabetes.




    noc

    Correction: EGFR Exon 20 Insertion Mutations Display Sensitivity to Hsp90 Inhibition in Preclinical Models and Lung Adenocarcinomas




    noc

    Surfactant Expression Defines an Inflamed Subtype of Lung Adenocarcinoma Brain Metastases that Correlates with Prolonged Survival

    Purpose:

    To provide a better understanding of the interplay between the immune system and brain metastases to advance therapeutic options for this life-threatening disease.

    Experimental Design:

    Tumor-infiltrating lymphocytes (TIL) were quantified by semiautomated whole-slide analysis in brain metastases from 81 lung adenocarcinomas. Multi-color staining enabled phenotyping of TILs (CD3, CD8, and FOXP3) on a single-cell resolution. Molecular determinants of the extent of TILs in brain metastases were analyzed by transcriptomics in a subset of 63 patients. Findings in lung adenocarcinoma brain metastases were related to published multi-omic primary lung adenocarcinoma The Cancer Genome Atlas data (n = 230) and single-cell RNA-sequencing (scRNA-seq) data (n = 52,698).

    Results:

    TIL numbers within tumor islands was an independent prognostic marker in patients with lung adenocarcinoma brain metastases. Comparative transcriptomics revealed that expression of three surfactant metabolism-related genes (SFTPA1, SFTPB, and NAPSA) was closely associated with TIL numbers. Their expression was not only prognostic in brain metastasis but also in primary lung adenocarcinoma. Correlation with scRNA-seq data revealed that brain metastases with high expression of surfactant genes might originate from tumor cells resembling alveolar type 2 cells. Methylome-based estimation of immune cell fractions in primary lung adenocarcinoma confirmed a positive association between lymphocyte infiltration and surfactant expression. Tumors with a high surfactant expression displayed a transcriptomic profile of an inflammatory microenvironment.

    Conclusions:

    The expression of surfactant metabolism-related genes (SFTPA1, SFTPB, and NAPSA) defines an inflamed subtype of lung adenocarcinoma brain metastases characterized by high abundance of TILs in close vicinity to tumor cells, a prolonged survival, and a tumor microenvironment which might be more accessible to immunotherapeutic approaches.




    noc

    Novel Insights into the Classification of Staphylococcal {beta}-Lactamases in Relation to the Cefazolin Inoculum Effect [Mechanisms of Resistance]

    Cefazolin has become a prominent therapy for methicillin-susceptible Staphylococcus aureus (MSSA) infections. However, an important concern is the cefazolin inoculum effect (CzIE), a phenomenon mediated by staphylococcal β-lactamases. Four variants of staphylococcal β-lactamases have been described based on serological methodologies and limited sequence information. Here, we sought to reassess the classification of staphylococcal β-lactamases and their correlation with the CzIE. We included a large collection of 690 contemporary bloodstream MSSA isolates recovered from Latin America, a region with a high prevalence of the CzIE. We determined cefazolin MICs at standard and high inoculums by broth microdilution. Whole-genome sequencing was performed to classify the β-lactamase in each isolate based on the predicted full sequence of BlaZ. We used the classical schemes for β-lactamase classification and compared it to BlaZ allotypes found in unique sequences using the genomic information. Phylogenetic analyses were performed based on the BlaZ and core-genome sequences. The overall prevalence of the CzIE was 40%. Among 641 genomes, type C was the most predominant β-lactamase (37%), followed by type A (33%). We found 29 allotypes and 43 different substitutions in BlaZ. A single allotype, designated BlaZ-2, showed a robust and statistically significant association with the CzIE. Two other allotypes (BlaZ-3 and BlaZ-5) were associated with a lack of the CzIE. Three amino acid substitutions (A9V, E112A, and G145E) showed statistically significant association with the CzIE (P = <0.01). CC30 was the predominant clone among isolates displaying the CzIE. Thus, we provide a novel approach to the classification of the staphylococcal β-lactamases with the potential to more accurately identify MSSA strains exhibiting the CzIE.




    noc

    Antibacterial Monoclonal Antibodies Do Not Disrupt the Intestinal Microbiome or Its Function [Experimental Therapeutics]

    Antibiotics revolutionized the treatment of infectious diseases; however, it is now clear that broad-spectrum antibiotics alter the composition and function of the host’s microbiome. The microbiome plays a key role in human health, and its perturbation is increasingly recognized as contributing to many human diseases. Widespread broad-spectrum antibiotic use has also resulted in the emergence of multidrug-resistant pathogens, spurring the development of pathogen-specific strategies such as monoclonal antibodies (MAbs) to combat bacterial infection. Not only are pathogen-specific approaches not expected to induce resistance in nontargeted bacteria, but they are hypothesized to have minimal impact on the gut microbiome. Here, we compare the effects of antibiotics, pathogen-specific MAbs, and their controls (saline or control IgG [c-IgG]) on the gut microbiome of 7-week-old, female, C57BL/6 mice. The magnitude of change in taxonomic abundance, bacterial diversity, and bacterial metabolites, including short-chain fatty acids (SCFA) and bile acids in the fecal pellets from mice treated with pathogen-specific MAbs, was no different from that with animals treated with saline or an IgG control. Conversely, dramatic changes were observed in the relative abundance, as well as alpha and beta diversity, of the fecal microbiome and bacterial metabolites in the feces of all antibiotic-treated mice. Taken together, these results indicate that pathogen-specific MAbs do not alter the fecal microbiome like broad-spectrum antibiotics and may represent a safer, more-targeted approach to antibacterial therapy.




    noc

    Encephalitozoon cuniculi Genotype III Evinces a Resistance to Albendazole Treatment in both Immunodeficient and Immunocompetent Mice [Experimental Therapeutics]

    Of four genotypes of Encephalitozoon cuniculi, E. cuniculi genotype II is considered to represent a parasite that occurs in many host species in a latent asymptomatic form, whereas E. cuniculi genotype III seems to be more aggressive, and infections caused by this strain can lead to the death of even immunocompetent hosts. Although albendazole has been considered suitable for treatment of Encephalitozoon species, its failure in control of E. cuniculi genotype III infection has been reported. This study determined the effect of a 100x recommended daily dose of albendazole on an Encephalitozoon cuniculi genotype III course of infection in immunocompetent and immunodeficient mice and compared the results with those from experiments performed with a lower dose of albendazole and E. cuniculi genotype II. The administration of the regular dose of abendazole during the acute phase of infection reduced the number of affected organs in all strains of mice and absolute counts of spores in screened organs. However, the effect on genotype III was minor. Surprisingly, no substantial effect was recorded after the use of a 100x dose of albendazole, with larger reductions seen only in the number of affected organs and absolute counts of spores in all strains of mice, implying variations in albendazole resistance between these Encephalitozoon cuniculi genotypes. These results imply that differences in the course of infection and the response to treatment depend not only on the immunological status of the host but also on the genotype causing the infection. Understanding how microsporidia survive in hosts despite targeted antimicrosporidial treatment could significantly contribute to research related to human health.




    noc

    Bemarituzumab Is Active in FGFR2b-High Gastroesophageal Adenocarcinoma [Clinical Trials]

    The FGFR2b inhibitor bemarituzumab was effective in high-FGFR2b gastroesophageal adenocarcinoma.




    noc

    Retinoic Acid Mediates Monocyte Differentiation and Immune Response [Immunology]

    Tumor-derived retinoic acid promotes monocyte differentiation into immunosuppressive macrophages.




    noc

    Greenock and Stockbridge: A tale of two Scotlands under coronavirus

    ON one of those Greenock afternoons when rain and sun fight for the day’s naming rights a statistic becomes flesh and blood. At the side of a four-lane highway bearing the weight of the town’s rush-hour traffic a young wheelchair-user approaches.




    noc

    Shocking moment man snatches handbag off woman in her 80s and knocks her to ground




    noc

    Netflix&apos;s The Innocence Files: The true cases of Levon Brooks, Kennedy Brewer and more

    Netflix has just launched another true crime docuseries - albeit this time with no tigers in sight - called The Innocence Files, which uncovers terrifying flaws in the American criminal justice system.




    noc

    People knocked out of bed as 5.5 magnitude earthquake hits Puerto Rico

    A 5.5-magnitude earthquake has hit near southern Puerto Rico, jolting many people from their beds and causing damage across the island.




    noc

    &#39;People Would Be So Receptive Right Now, and We Can&#39;t Knock on Doors.&#39;

    Brenda Francis settled into the Kingdom Hall in Calhoun, Georgia, in mid-March, surrounded by dozens of familiar faces. Signs cautioning against shaking hands and hugging were posted around the room. It felt weird to her but was certainly understandable with the threat of an outbreak looming. She herself already had stocked up on some masks and gloves.When it came time for members to comment on the Bible readings, Francis noticed the microphones typically passed around the room were now attached to the end of long poles.That was the moment Francis, a 69-year-old widow living in a small, semirural community in the South, realized just how dramatically the coronavirus pandemic was about to reshape her spiritual life, more than anything ever had in the 47 years since she was baptized as a Jehovah's Witness.A few days after the boom mics came out in the Kingdom Hall, word came down from the group's headquarters that, in the interest of safety, Jehovah's Witnesses should stop witnessing, its practice of in-person attempts at converting people to the group."People would be so receptive right now," she said of her ministry, "and we can't knock on doors."Across the country, most religious groups have stopped coming together in large numbers to pray and hold services, in keeping with stay-at-home orders. They have improvised with online preaching and even drive-in services as the faithful sit in cars. Mormons have stopped going door to door in the United States and called home many missionaries working abroad.Jehovah's Witnesses -- with 1.3 million U.S. members who hand out brochures on sidewalks and subway platforms and ring doorbells -- are one of the most visible religious groups in the nation. Members are called on to share Scriptures in person with nonmembers, warning of an imminent Armageddon and hoping to baptize them with the prospect of living forever.The decision to stop their ministries was the first of its kind in the nearly 150 years of the group's existence. It followed anguished discussions at Watchtower headquarters, with leaders deciding March 20 that knocking on doors would leave the impression that members were disregarding the safety of those they hoped to convert."This was not an easy decision for anybody," said Robert Hendriks, the group's U.S. spokesman. "As you know, our ministry is our life."It was for Francis, who became a Jehovah's Witness when she was in her 20s with a newborn and a member knocked on her door in Tennessee and persuaded her to attend a Kingdom Hall meeting. She converted. Her family was angry that she no longer came to holiday gatherings; the group doesn't believe in celebrating holidays or birthdays. Jehovah's Witnesses became her new family.The more she studied the Bible, the more she came to believe it led to eternal life. She needed to spread the word.Showing up cold on someone's doorstep didn't come naturally. She was so shy that once, she recalled, her high school principal -- "this huge Goliath guy" -- stood on her foot in a crowded hallway; she didn't say a word but waited in pain for him to move. She had considered a career going door to door as a Mason Shoes saleswoman, but after receiving a catalog, she never mustered the courage to even try to make a sale.To her, witnessing was different. Her faith had helped her stop smoking. It gave her meaning. She had seen people clean up their lives after attending meetings at Kingdom Hall."By the time I did go to doors, I was so convinced this was the right thing to do that I had no nervousness," Francis said.Through the years, she learned to build her pitch around a theme -- a Bible verse or a current event -- and tried not to sound rehearsed."You don't want to sound like a robot," she said. "You work from the heart. You want enthusiasm."Early this year, Francis had been seeing reports on Facebook about the virus sweeping through Wuhan, China. The host of a show she watched on YouTube, Peak Prosperity, had been warning that the outbreak could spread internationally.She bought masks and face shields, just in case. She started using plastic grocery bags to cover the gas pump handle when she filled up her tank.By early March, the virus still hadn't hit Gordon County, where Francis lives. But the possibility was weighing on her mind. The message on her favorite YouTube show was getting more dire as the host, Chris Martenson, a financial guru-turned-pandemic early warner, ratcheted up his pleadings for viewers to prepare themselves.Francis' 27-year-old granddaughter has a compromised immune system. As a senior citizen, she herself was vulnerable. She did what she always has done and channeled her own feelings into her door-knocking ministry. Do you think, she would ask people as she carpooled with other members to canvass the county, that the virus is a sign of the end of the world?"No one was paying much attention," she said.Elsewhere, in places like New York where infections were starting to climb, Jehovah's Witnesses members were feeling the pinch on their ministries.One of them, Joe Babsky, had been easing into conversations with members of his Planet Fitness gym in the Bronx for weeks. He knew them by first name only: Jerry, who had lost more than 100 pounds; Jason, who seemed to spend an hour on each body part; Bernie, a 78-year-old who was more fit than men half his age. Babsky had shown a few of them Bible verses and had made progress recently with Bernie discussing the logic behind the existence of an intelligent creator.Then the gym closed."All those conversations and others were cut short," Babsky said.Life continued as normal in Francis' town of Calhoun. She was convinced things were about to change, but she was too embarrassed to wear a mask -- until an encounter in Costco when a passing shopper coughed without covering her mouth.In mid-March, her Kingdom Hall meetings went virtual. Members logged into Zoom to share Bible Scriptures. Francis settled on one that she thought would resonate as she knocked on doors in her neighborhood across the county, which had by then registered a handful of COVID-19 cases.At the doorstep, Francis would start her pitch by asking people if they could make one thing in the world go away, what would it be? If the answer had to do with the pandemic, she would recite a couple of verses from the book of Luke:"There will be great earthquakes, and in one place after another food shortages and pestilences; and there will be fearful sights and from heaven great signs."All the signs were clear, she would announce. Armageddon was near. Her message finally seemed to be resonating with people.And then she got word to stop knocking on doors."This has been so much a part of our lives, so it was like, wow," she said. "I have often envisioned in paradise where going door to door would not be a thing because everyone knows God."This was not paradise.But Francis was convinced that the end of the world was not far away. There were just too many signs, she said. And so she and many other Jehovah's Witnesses members were more compelled than ever to witness any way they could. Many began writing letters or making phone calls to anyone whose numbers they had managed to collect before the pandemic hit.Masked and gloved, Francis hands out pamphlets and cards with her phone number on them to fellow shoppers at the grocery store.Last week, she sent a text to a woman in Hawkinsville, Georgia, a few miles away, whom she had been contacting from time to time. The woman said her restaurant had to close because of the pandemic and her brother-in-law was sick with the virus. A couple of days later he died.Francis texted Scriptures to the woman and told her that soon all the sickness on Earth would be over; all sins would be forgiven; paradise was near.The next day she received a written response: "Thank you so much for the information. It was such a comfort."This article originally appeared in The New York Times.(C) 2020 The New York Times Company





    noc

    The Innocence Files review: Netflix&apos;s devastating documentary exposes how wrongful convictions can tear apart lives

    Men locked away for decades over crimes they didn't commit share their stories in this startling new series




    noc

    Quiz: Viewers convinced Ingrams are innocent as &apos;absolutely incredible&apos; show draws to a close

    Many fans praised Helen McRory's 'bad-ass' performance and the unexpected musical sequence




    noc

    Gareth Malone shares anger after son is knocked over by a jogger

    The choir leader told Twitter followers how a runner failed to maintain a two metre distance and "fell" on his young son




    noc

    Manchester United told Jadon Sancho won&apos;t come at knock-down transfer fee after coronavirus shutdown

    Manchester United have been warned Borussia Dortmund remain in a "strong financial position" despite the economic uncertainty brought about by the coronavirus pandemic.




    noc

    Scientists have created new nanocomposite from gold and titanium oxide

    ITMO University researchers together with their colleagues from France and the USA have demonstrated how a femtosecond laser can be used to tune the structure and nanocomposite properties for titanium dioxide films filled with gold nanoparticles.




    noc

    Many WA businesses already struggling fear they've just been hit with a knockout blow

    The tourism industry warns if Virgin Australia collapses it could deliver a knockout blow to many WA businesses who were already on their knees as a result of coronavirus.




    noc

    Jason Manford 'livid' after being knocked back by Tesco for a job

    The Salford comic applied for a job at the Aldery Road Express store in Wilmslow




    noc

    Iceland has given Jason Manford a very generous offer after Tesco knockback

    Iceland has put in a job offer for the Salford comic after Tesco didn't hire him




    noc

    Kansas Man Charged with Immigration Crimes in Connection with 1994 Genocide in Rwanda

    Lazare Kabaya Kobagaya, 82, of Topeka, Kan., was arrested today on charges of naturalization fraud and misuse of an alien registration card. According to the indictment, Kobagaya allegedly participated in genocidal activities during the 1994 Rwandan conflict including mobilizing attackers to commit arson and murder. Kobagaya is alleged to have failed to disclose his alleged participation in these activities during his immigration and naturalization processes.



    • OPA Press Releases

    noc

    ConocoPhillips Company and Sasol North America Agree to Reimburse Costs for Calcasieu Estuary, Bayou Verdine Cleanup

    The Department of Justice, the Environmental Protection Agency and the United States Attorney’s Office announced today, the settlement of claims against ConocoPhillips Company and Sasol North America Inc. to resolve their liability to EPA under CERCLA for contamination in the Calcasieu Estuary of Louisiana.



    • OPA Press Releases

    noc

    Justice Department Reaches Agreement with Rappahannock, Virginia, on Bailout from the Voting Rights Act

    The Justice Department announced that it has reached an agreement with Rappahannock County, Va., that will allow for the county and its two political subdivisions to bail out from their status as “covered jurisdictions” under the special provisions of the Voting Rights Act.



    • OPA Press Releases

    noc

    Antiques Dealer Pleads Guilty in Manhattan Federal Court to Crimes Relating to Illegal Trafficking of Endangered Rhinoceros Horns

    David Hausman, an antiques dealer in Manhattan, pleaded guilty today in Manhattan federal court to obstruction of justice and creating false records, in relation to illegal rhinoceros horn trafficking.



    • OPA Press Releases

    noc

    Members of Smuggling Ring Plead Guilty in Los Angeles to Crimes Relating to Illegal Trafficking of Endangered Rhinoceros Horn

    Three defendants pleaded guilty today to charges of conspiracy, smuggling, Lacey Act violations, money laundering and tax fraud for their roles in the international illegal trafficking of rhinoceros horn. All of the defendants were charged in February 2012 as part of “Operation Crash,” a nationwide U.S. Fish and Wildlife Service crackdown on those involved in the black market trade of endangered rhinoceros horn.



    • OPA Press Releases

    noc

    Antiques Dealer Sentenced in New York City for Crimes Relating to Illegal Trafficking of Endangered Rhinoceros Horns

    David Hausman, an antiques dealer in Manhattan, was sentenced today in Manhattan federal court to six months in jail for obstruction of justice and creating false records in connection with illegal rhinoceros horn trafficking.



    • OPA Press Releases

    noc

    Smuggling Ring Sentenced in Los Angeles for Criminal Trafficking of Endangered Rhinoceros Horn

    Vinh Chuong “Jimmy” Kha, 50, and Felix Kha 26, were sentenced today in federal district court in Los Angeles to serve 42 and 46 months, respectively, in prison for crimes related to illegal international trafficking of rhinoceros horn.



    • OPA Press Releases

    noc

    Irish National Pleads Guilty in New York to Crimes Relating to Illegal Trafficking of Endangered Rhinoceros Horns

    Michael Slattery Jr., 25, an Irish national, pleaded guilty today in federal court in Brooklyn, N.Y., to conspiracy to violate the Lacey Act in relation to illegal rhinoceros horn trafficking, announced Robert G. Dreher, Acting Assistant Attorney General for the Environment and Natural Resources Division of the Department of Justice, and Loretta E. Lynch, U.S. Attorney for the Eastern District of New York.



    • OPA Press Releases

    noc

    New Hampshire Man Charged with Passing Fraudulent Documents in Connection with His Sale of Black Rhinoceros Horns for $35,000

    Ari B. Goldenberg, 46, of Milton, N.H., was charged today with trafficking in and making a false record for illegally selling a black rhinoceros head mount to an undercover U.S. Fish & Wildlife Service (FWS) special agent.



    • OPA Press Releases

    noc

    Irish National Sentenced to Serve 14 Months in Prison for Trafficking of Endangered Rhinoceros Horns

    Michael Slattery Jr., an Irish national, was sentenced in federal court in Brooklyn, N.Y., today to serve 14 months in prison to be followed by three years of supervised release.



    • OPA Press Releases

    noc

    Two California Men Indicted for Selling Endangered Black Rhinoceros Horns

    Edward N. Levine, 63, of Mill Valley, Calif., and Lumsden W. Quan, 46, of San Francisco, were indicted by a federal grand jury in Las Vegas today for the illegal sale of two horns from an endangered black rhinoceros.



    • OPA Press Releases

    noc

    Genetic and clinical correlates of entosis in pancreatic ductal adenocarcinoma




    noc

    Author Correction: From melanocytes to melanomas




    noc

    The nuclear oncoprotein Fra-1: a transcription factor knocking on therapeutic applications’ door




    noc

    Molecular profiling of stroma highlights stratifin as a novel biomarker of poor prognosis in pancreatic ductal adenocarcinoma




    noc

    The expression of YAP1 is increased in high-grade prostatic adenocarcinoma but is reduced in neuroendocrine prostate cancer




    noc

    Genocea's mark on malaria

    Genocea has identified an immunological imprint in patients with malaria and is using a $1.2 million grant from the Gates Foundation to turn the findings into a vaccine.




    noc

    McLaren won't be getting knocked out in Q1 for long - Alonso

    Fernando Alonso is confident McLaren will not be getting knocked out of Q1 for long this season despite his first qualifying session with McLaren leaving him 18th on the grid at the Malaysian Grand Prix




    noc

    When Is It OK to Knock Down Old Houses?

    The largest collection of prefab houses in the UK is about to be demolished. Built by German and Italian prisoners of war in 1945, these small bungalows are a remnant of war-time years when housing was at a premium.




    noc

    Minimalist Monocabin is a modular 291 sq. ft. prefab

    This modern prefab from Italy is conceived with energy efficiency and ease of assembly in mind.




    noc

    ConocoPhillips Withdraws From Controversial Amazon Oil Project

    At the ConocoPhillips annual shareholder meeting last week, CEO James Mulva announced the company's withdrawal from the oil-drilling project in Block 39 of the northern Peruvian Amazon. It was a highly controversial project