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  • 1
    Language: English
    In: mBio, 01 November 2018, Vol.9(6), p.e02184-18
    Description: P. aeruginosa is a soil dwelling bacterium and a plant pathogen, and it also causes life-threatening infections in humans. Thus, P. aeruginosa thrives in diverse environments and over a broad range of temperatures. Some P. aeruginosa strains rely on the CRISPR-Cas adaptive immune system as a phage defense mechanism. Our discovery that low temperatures increase CRISPR adaptation suggests that the rarely occurring but crucial naive adaptation events may take place predominantly under conditions of slow growth, e.g., during the bacterium’s soil dwelling existence and during slow growth in biofilms.Clustered regularly interspaced short palindromic repeat (CRISPR)-associated (CRISPR-Cas) systems are adaptive defense systems that protect bacteria and archaea from invading genetic elements. In Pseudomonas aeruginosa, quorum sensing (QS) induces the CRISPR-Cas defense system at high cell density when the risk of bacteriophage infection is high. Here, we show that another cue, temperature, modulates P. aeruginosa CRISPR-Cas. Increased CRISPR adaptation occurs at environmental (i.e., low) temperatures compared to that at body (i.e., high) temperature. This increase is a consequence of the accumulation of CRISPR-Cas complexes, coupled with reduced P. aeruginosa growth rate at the lower temperature, the latter of which provides additional time prior to cell division for CRISPR-Cas to patrol the cell and successfully eliminate and/or acquire immunity to foreign DNA. Analyses of a QS mutant and synthetic QS compounds show that the QS and temperature cues act synergistically. The diversity and level of phage encountered by P. aeruginosa in the environment exceed that in the human body, presumably warranting increased reliance on CRISPR-Cas at environmental temperatures.
    Keywords: Crispr ; Phage ; Pseudomonas ; Quorum Sensing ; Growth Rate ; Biology
    ISSN: 21612129
    E-ISSN: 2150-7511
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  • 2
    Language: English
    In: The Journal of Thoracic and Cardiovascular Surgery, June 2018, Vol.155(6), pp.2674-2681
    Description: Safety net hospitals provide care mostly to low-income, uninsured, and vulnerable populations, in whom delays in cancer screening are established barriers. Socioeconomic barriers might pose important challenges to the success of a lung cancer screening program at a safety net hospital. We aimed to determine screening follow-up compliance, rates of diagnostic and treatment procedures, and the rate of cancer diagnosis in patients classified as category 4 by the Lung CT Screening Reporting and Data System (Lung-RADS 4). We conducted a retrospective review of all patients enrolled in our multidisciplinary lung cancer screening program between March 2015 and July 2016. Demographics, smoking status, Lung-RADS score, and number of diagnostic and therapeutic interventions and cancer diagnoses were captured. A total of 554 patients were screened over a 16-month period. The mean patient age was 63 years (range, 47-85 years), and 60% were male. The majority (92%; 512 of 554) were classified as Lung-RADS 1 to 3, and 8% (42 of 554) were classified as Lung-RADS 4. Among the Lung-RADS 4 patients, 98% (41 of 42) completed their recommended follow-up; 29% (12 of 42) underwent a diagnostic procedure, for an overall diagnostic intervention rate of 2% (12 of 554). Eleven of these 12 patients had cancer, and 1 patient had sarcoidosis. The overall rate of surgical resection was 0.9% (5 of 554), and the rate of diagnostic intervention for noncancer diagnosis was 0.1% (1 of 554). Implementation of a multidisciplinary lung cancer screening program at a safety net hospital is feasible. Compliance with follow-up and interventional recommendations in Lung-RADS 4 patients was high despite anticipated social challenges. Overall diagnostic and surgical resection rates and interventions for noncancer diagnosis were low in our initial experience.
    Keywords: Lung Cancer Screening ; Safety Net Hospital ; Socioeconomic Barriers ; Lung-Rads ; Follow-Up ; Compliance
    ISSN: 0022-5223
    E-ISSN: 1097-685X
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  • 3
    Language: English
    In: Qualitative Social Work, January 2017, Vol.16(1), pp.113-130
    Description: Social support is a key, yet elusive resource for HIV patients living in poverty in Lima, Peru. Despite a greater need for health services and encouragement from others, economic restraints, stigma, and trouble negotiating a fractured health system act as hurdles to accessing support. In this study, 33 people with HIV and 15 of their treatment supporters were interviewed upon initiation of antiretroviral therapy in order to understand changes in social support during this critical time, and how these changes affected their well-being. Everyone’s social network underwent dramatic transformation, while some were rejected upon disclosure by people they knew, many successfully trimmed their social circles to a few trusted parties. Treatment supporters were most frequently the first to whom they disclosed their HIV status, and most backed the person with HIV, although sometimes out of obligation. HIV peers became a vital new source of strength. Ultimately, people with HIV who successfully reorganized their social network drew personal strength and self-worth from new and old relationships in their lives.
    Keywords: Social Support ; HIV ; Emotional Support ; Qualitative ; Art Initiation ; Social Welfare & Social Work
    ISSN: 1473-3250
    E-ISSN: 1741-3117
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  • 4
    Language: English
    In: Environmental Research, October 2017, Vol.158, pp.1-6
    Description: Although consumption of Tetraodontidae species is prohibited in the EU, intoxications are still reported. The evaluation of tetrodotoxins (TTXs) by mass spectrometry (LC-MS/MS and LC-HRMS) and a screening immunoassay (mELISA) in tetraodontid fishes caught along the Western Mediterranean Sea revealed high concentrations of TTXs in while no TTXs were identified in . and individuals. The high TTXs content found in the . analysed herein demonstrate the occurrence of highly toxic puffer fish in the Western Mediterranean Sea. Being . a recent invasive species in the Mediterranean, surveillance, risk assessment and risk management measures are necessary. The strategy used within this research work could be a valuable tool for future food safety monitoring. Presence of tetrodotoxins (TTXs) in different puffer fish species caught off the Spanish coast (Western Mediterranean Sea) was evaluated by liquid chromatography coupled to mass spectrometry (LC-MS/MS). The only toxic species was , a recently invasive species in the Mediterranean. The toxin profile was confirmed by high resolution mass spectrometry (LC-HRMS). An immunoassay (mELISA) also showed TTX presence, providing complementary functional information.
    Keywords: Tetrodotoxin ; Lagocephalus Sceleratus ; Puffer Fish ; Mass Spectrometry ; Melisa ; Environmental Sciences ; Public Health
    ISSN: 0013-9351
    E-ISSN: 1096-0953
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  • 5
    In: The Journal of Experimental Medicine, 2018, Vol.215(3), p.877-893
    Description: Perry et al. show that myeloid-targeted immunotherapy with a combination of anti-CD40 and CSF-1R inhibition synergistically induces a proinflammatory microenvironment that suppresses CPI-resistant tumors in a TNF-α– and IFN-γ–dependent manner. Eliciting effective antitumor immune responses in patients who fail checkpoint inhibitor therapy is a critical challenge in cancer immunotherapy, and in such patients, tumor-associated myeloid cells and macrophages (TAMs) are promising therapeutic targets. We demonstrate in an autochthonous, poorly immunogenic mouse model of melanoma that combination therapy with an agonistic anti-CD40 mAb and CSF-1R inhibitor potently suppressed tumor growth. Microwell assays to measure multiplex protein secretion by single cells identified that untreated tumors have distinct TAM subpopulations secreting MMP9 or cosecreting CCL17/22, characteristic of an M2-like state. Combination therapy reduced the frequency of these subsets, while simultaneously inducing a separate polyfunctional inflammatory TAM subset cosecreting TNF-α, IL-6, and IL-12. Tumor suppression by this combined therapy was partially dependent on T cells, and on TNF-α and IFN-γ. Together, this study demonstrates the potential for targeting TAMs to convert a “cold” into an “inflamed” tumor microenvironment capable of eliciting protective T cell responses.
    Keywords: Research Articles ; 307 ; 311 ; 314
    ISSN: 0022-1007
    E-ISSN: 1540-9538
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  • 6
    Language: English
    In: Nature genetics, July 2018, Vol.50(7), pp.912-919
    Description: Intelligence is highly heritable and a major determinant of human health and well-being. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
    Keywords: Intelligence -- Genetics
    ISSN: 10614036
    E-ISSN: 1546-1718
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  • 7
    Language: English
    In: Cellular Signalling, 2003, Vol.15(1), pp.103-113
    Description: The muscarinic agonist carbachol stimulated phospholipase D (PLD) in rat submandibular gland (RSMG) ductal cells in a time and concentration-dependent manner. This effect was inhibited by chelation of extracellular calcium with ethylene glycol-bis(β-aminoethyl ether)- N , N , N ′, N ′-tetraacetic acid (EGTA). PLD could also be activated by epinephrine and AlF 4 − , two polyphosphoinositide-specific phospholipase C (PPI-PLC) activators, and by the phorbol ester o -tetradecanoylphorbol 13-acetate (TPA) which activates protein kinase C (PKC). Ionomycin and thapsigargin only slightly increased PLD activity. Ortho -vanadate, a tyrosine phosphatase inhibitor, also stimulated PLD activity. Both carbachol and o -vanadate increased the formation of inositol phosphates and the tyrosine phosphorylation of at least two proteins (55–60 and 120 kDa). Calphostin C (a PKC inhibitor), U73122 (a PPI-PLC inhibitor) and genistein (a tyrosine kinase inhibitor) blocked the activation of PLD, of PLC and the phosphorylation of tyrosyl residues in response to carbachol and vanadate. Taken together, these results suggest that rat submandibular gland ductal cells express a calcium-dependent PLD activity. This enzyme is regulated by carbachol via a PLC–PKC–tyrosine kinase pathway.
    Keywords: Salivary Glands ; Carbachol ; Protein Kinase C ; Tyrosine Kinase ; O-Vanadate ; Phospholipase C ; Biology
    ISSN: 0898-6568
    E-ISSN: 1873-3913
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  • 8
    Language: English
    In: The Journal of the Association of Nurses in AIDS Care : JANAC, 13 February 2019
    Description: Little evidence exists about the emotional experiences of mothers with HIV, and a better understanding is essential to support their emotional health and treatment adherence. We describe the emotional experiences of eight mothers who initiated antiretroviral therapy during pregnancy or within a few years of childbirth in Lima, Peru. An interpretive phenomenological approach was used, and the following themes emerged: (a) emotions involved in diagnosis and disclosure, (b) the meaning of motherhood with HIV, (c) the mothers' roles in seeking and maintaining relationships with partners and families, and (d) mechanisms for resilience and emotional recovery. Participants experienced sadness and denial after diagnosis, which gave way to emotional recovery. Participant abilities to find refuge in caring for children and coordinating support from loved ones proved to be essential. Participants recognized that intense emotions motivated them to seek creative solutions and cited personal growth as an important outcome.
    ISSN: 10553290
    E-ISSN: 1552-6917
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