1,851 research outputs found

    Letter from Susan L. Mills to John Muir, 1907 Sep 23.

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    MILLS COLLEGE. CALIF.PRESIDENT\u27S OFFICE Sept. 23, \u2707. My dear Mr. Muir: I write to ask a great favor of you. I know you do not like to speak in public but our family of two hundred and fifty would like very much to have you instruct and honor us by speaking to us here. I have been asked a number of times to invite you to come and speak to us and any day which would be convenient to you we should be most happy to have you with us. We have our lectures on Wednesday at half past two so one coming to us may lecture and leave any hour after the lecture. I knew your good wife well and your father and mother also when our home was in Benicia.We are so glad to read everything that comes from your pen but we are anxious to see you face to face and assure you of our appreciation of your great and good work and so I beg that you will not disappoint us.With kind regards and best wishes, I am, yours very sincerely. [illegible]0392

    Inhibitory activity of Lactobacillus plantarum LMG P-26358 against Listeria innocua when used as an adjunct starter in the manufacture of cheese

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    Lactobacillus plantarum LMG P-26358 isolated from a soft French artisanal cheese produces a potent class IIa bacteriocin with 100% homology to plantaricin 423 and bacteriocidal activity against Listeria innocua and Listeria monocytogenes. The bacteriocin was found to be highly stable at temperatures as high as 100°C and pH ranges from 1-10. While this relatively narrow spectrum bacteriocin also exhibited antimicrobial activity against species of enterococci, it did not inhibit dairy starters including lactococci and lactobacilli when tested by well diffusion assay (WDA). In order to test the suitability of Lb. plantarum LMG P-26358 as an anti-listerial adjunct with nisin-producing lactococci, laboratory-scale cheeses were manufactured. Results indicated that combining Lb. plantarum LMG P-26358 (at 108 colony forming units (cfu)/ml) with a nisin producer is an effective strategy to eliminate the biological indicator strain, L. innocua. Moreover, industrial-scale cheeses also demonstrated that Lb. plantarum LMG P-26358 was much more effective than the nisin producer alone for protection against the indicator. MALDI-TOF mass spectrometry confirmed the presence of plantaricin 423 and nisin in the appropriate cheeses over an 18 week ripening period. A spray-dried fermentate of Lb. plantarum LMG P-26358 also demonstrated potent anti-listerial activity in vitro using L. innocua. Overall, the results suggest that Lb. plantarum LMG P-26358 is a suitable adjunct for use with nisin-producing cultures to improve the safety and quality of dairy products

    Characterization of an electron conduit between bacteria and the extracellular environment

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    A number of species of Gram-negative bacteria can use insoluble minerals of Fe(III) and Mn(IV) as extracellular respiratory electron acceptors. In some species of Shewanella, deca-heme electron transfer proteins lie at the extracellular face of the outer membrane (OM), where they can interact with insoluble substrates. To reduce extracellular substrates, these redox proteins must be charged by the inner membrane/periplasmic electron transfer system. Here, we present a spectro-potentiometric characterization of a trans-OM icosa-heme complex, MtrCAB, and demonstrate its capacity to move electrons across a lipid bilayer after incorporation into proteoliposomes. We also show that a stable MtrAB subcomplex can assemble in the absence of MtrC; an MtrBC subcomplex is not assembled in the absence of MtrA; and MtrA is only associated to the membrane in cells when MtrB is present. We propose a model for the modular organization of the MtrCAB complex in which MtrC is an extracellular element that mediates electron transfer to extracellular substrates and MtrB is a trans-OM spanning ß-barrel protein that serves as a sheath, within which MtrA and MtrC exchange electrons. We have identified the MtrAB module in a range of bacterial phyla, suggesting that it is widely used in electron exchange with the extracellular environment

    Problem Behavior of Dementia Patients Predicts Low-Grade Hypercoagulability in Spousal Caregivers

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    Background. Low-grade hypercoagulability might be one pathway to explain how the chronic stress of dementia caregiving increases cardiovascular disease risk, but the specific aspects of caregiver stress that elicit hypercoagulability are elusive. We hypothesized that dementia patients' problem behaviors and negative reactions of caregivers to these behaviors would relate to hypercoagulability in caregivers. Methods. One hundred and eight participants (mean age 74 ± 8 years, 70% women) providing in-home care for their spouse with Alzheimer's disease were examined. Caregivers were interviewed about the number of 24 predefined patient problem behaviors in the previous week (range 0-24) and how upset or bothered they felt in response to these behaviors (total score 0-96). Von Willebrand factor, plasminogen activator inhibitor-1, and D-dimer were determined in plasma and standardized z-scores of their concentrations summed into a procoagulant index. Results. Greater number of problem behaviors (ΔR2 = 0.046, p = .014) and negative reactions of caregivers to these behaviors (ΔR2 = 0.044, p = .017) were associated with greater procoagulant index after controlling for sociodemographic factors, major cardiovascular risk factors, health habits, and health problems. However, the number of and reaction to problem behaviors did not significantly predict procoagulant activity independent from each other. Post hoc analysis revealed a positive association between the number of problem behaviors and D-dimer (p = .010, ΔR2 = 0.053), even when controlling for negative reactions (p = .033, ΔR2 = 0.036). Caregiver reaction to problem behaviors was not significantly associated with any procoagulant factor individually. Conclusion. Alzheimer patients' problem behavior and their negative appraisal by the caregiver may contribute to the chronic low-grade hypercoagulable state in dementia caregiver

    Large, persistent epidemic of adenovirus type 4-associated acute respiratory disease in U.S. army trainees.

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    In May 1997, a large, persistent epidemic of adenovirus type 4-associated acute respiratory disease began at Fort Jackson, South Carolina, the largest army basic training center. The epidemic lasted until December and declined when vaccine administration resumed. More than 1,000 male and female trainees were hospitalized; 66.1% of those hospitalized had an adenovirus type 4 isolate

    Mitochondrial uncoupling links lipid catabolism to Akt inhibition and resistance to tumorigenesis

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    To support growth, tumour cells reprogramme their metabolism to simultaneously upregulate macromolecular biosynthesis while maintaining energy production. Uncoupling proteins (UCPs) oppose this phenotype by inducing futile mitochondrial respiration that is uncoupled from ATP synthesis, resulting in nutrient wasting. Here using a UCP3 transgene targeted to the basal epidermis, we show that forced mitochondrial uncoupling inhibits skin carcinogenesis by blocking Akt activation. Similarly, Akt activation is markedly inhibited in UCP3 overexpressing primary human keratinocytes. Mechanistic studies reveal that uncoupling increases fatty acid oxidation and membrane phospholipid catabolism, and impairs recruitment of Akt to the plasma membrane. Overexpression of Akt overcomes metabolic regulation by UCP3, rescuing carcinogenesis. These findings demonstrate that mitochondrial uncoupling is an effective strategy to limit proliferation and tumorigenesis through inhibition of Akt, and illuminate a novel mechanism of crosstalk between mitochondrial metabolism and growth signalling

    HIV p24-Specific Helper T Cell Clones From Immunised Primates Recognize Highly Conserved Regions of HIV-l

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    We have investigated Th cell recognition of the HIV core protein p24 by using CD4+ T cell clones derived from cynomolgus macaques immunized with hybrid HIV p24:Ty virus-like particles (VLP). T cell lines from two immunized animals responded to p24:Ty-VLP, control Ty-VLP, purified p24, and whole inactivated HIV, indicating the presence of T cells specific for p24 as well as the Ty carrier protein. The HIV determinants recognized by the T cell lines were identified by using a series of overlapping peptides synthesized according to the sequence of p24. Both T cell lines recognized peptide 11 (amino acids 235-249) and peptide 14 (amino acids 265- 279). In addition, one T cell line also responded to peptide 9 (amino acids 215-229). Definitive identification of two T cell epitopes on p24 was confirmed at the clonal level: from a total of four T cell clones generated from one of the T cell lines, two respond specifically to peptide 11 and two to peptide 14. The T cell clones were CD4' and MHC class 11-restricted and secreted IL-2 in response to stimulation with purified p24, inactivated HIV or a single synthetic peptide. The specificityof the Th clones for variant peptides demonstrated cross-reactivity with two simian immunodeficiency virus isolates, but only limited responses to HIV-2 sequences. However, the Th cell epitopes identified on p24 are highly conserved between 12 HIV-1 isolates and were recognized by both of the immunized primates. These sequences may therefore be useful for priming a broadly reactive immune response to HIV-1

    Steps on the Path to Clinical Translation: A workshop by the British and Irish Chapter of the ISMRM

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    The British and Irish Chapter of the International Society for Magnetic Resonance in Medicine (BIC-ISMRM) held a workshop entitled "Steps on the path to clinical translation" in Cardiff, UK, on 7th September 2022. The aim of the workshop was to promote discussion within the MR community about the problems and potential solutions for translating quantitative MR (qMR) imaging and spectroscopic biomarkers into clinical application and drug studies. Invited speakers presented the perspectives of radiologists, radiographers, clinical physicists, vendors, imaging Contract/Clinical Research Organizations (CROs), open science networks, metrologists, imaging networks, and those developing consensus methods. A round-table discussion was held in which workshop participants discussed a range of questions pertinent to clinical translation of qMR imaging and spectroscopic biomarkers. Each group summarized their findings via three main conclusions and three further questions. These questions were used as the basis of an online survey of the broader UK MR community
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