Effects of phonological feedback on the selection of syntax: Evidence from between-language syntactic priming

Research on word production in bilinguals has often shown an advantage for cognate words. According to some accounts, this cognate effect is caused by feedback from a level that represents information about phonemes (or graphemes) to a level concerned with the word. In order to investigate whether phonological feedback influences the selection of words and syntactic constructions in late bilinguals, we investigated syntactic priming between Dutch and English genitive constructions (e.g., the fork of the girl vs. the girl’s fork). The head nouns of prime and target constructions were always translation equivalents. Half of these were Dutch–English cognates with a large phonological overlap (e.g., vork–fork), the other half were non-cognates that had very few phonemes in common (e.g., eend–duck). Cognate status boosted between-language syntactic priming. Further analyses showed a continuous effect of phonological overlap for cognates and non-cognates, indicating that this boost was at least partly caused by feedback from the translation equivalents’ shared phonemes

Grazing‐angle characterization of photosynthetic oxygen evolution protein monolayers

Variable‐period x‐ray standing wave (XSW) spectroscopy has been shown to be a practical probe for studying metalloproteins. The photosynthetic oxygen evolving complex (OEC) is a transmembrane multipolypeptide complex that catalyzes the oxidation of water to dioxygen. The OEC contains Mn, Ca, and Cl and is potentially amenable to study by XSW. In this feasibility study, preliminary results on OEC samples deposited on Au mirrors are discussed. First XSW measurements from the SSRL grazing‐incidence setup are presented. © 1996 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70867/2/RSINAK-67-9-3364-5.pd

Salmonella flagellin activates NAIP/NLRC4 and canonical NLRP3 inflammasomes in human macrophages

Infection of human macrophages with Salmonella enterica serovar Typhimurium (S. Typhimurium) leads to inflammasome activation. Inflammasomes are multi-protein complexes facilitating caspase–1 activation and subsequent gasdermin D-mediated cell death and interleukin–1β and interleukin–18 cytokine release. The NAIP/NLRC4 inflammasome is activated by multiple bacterial protein ligands including flagellin from the flagellum and the needle protein PrgI from the S. Typhimurium type III secretion system. Here we show that transfected ultrapure flagellin from S. Typhimurium induced cell death and cytokine secretion in THP–1 cells and primary human monocyte-derived macrophages (hMDM). In THP–1 cells, NAIP/NLRC4 and NLRP3 played redundant roles in inflammasome activation during infection with S. Typhimurium. Knock-out of NAIP or NLRC4 in THP–1 cells revealed that flagellin, but not PrgI, now activated the NLRP3 inflammasome through a ROS- and/or cathepsin-dependent mechanism that was independent of caspase–4/5 activity. In conclusion, our data suggest that NLRP3 can be activated by flagellin to act as a “safety net” to maintain inflammasome activation under conditions of suboptimal NAIP/NLRC4 activation, as observed in THP–1 cells, possibly explaining the redundant role of NLRP3 and NAIP/NLRC4 during S. Typhimurium infection.Wellcome Trus

Frequency Limits on Naked-Eye Optical Transients Lasting from Minutes to Years

How often do bright optical transients occur on the sky but go unreported? To constrain the bright end of the astronomical transient function, a systematic search for transients that become bright enough to be noticed by the unaided eye was conducted using the all-sky monitors of the Night Sky Live network. Two fisheye continuous cameras (CONCAMs) operating over three years created a data base that was searched for transients that appeared in time-contiguous CCD frames. Although a single candidate transient was found (Nemiroff and Shamir 2006), the lack of more transients is used here to deduce upper limits to the general frequency of bright transients. To be detected, a transient must have increased by over three visual magnitudes to become brighter than visual magnitude 5.5 on the time scale of minutes to years. It is concluded that, on the average, fewer than 0.0040 ($t_{dur} / 60$ seconds) transients with duration $t_{dur}$ between minutes and hours, occur anywhere on the sky at any one time. For transients on the order of months to years, fewer than 160 ($t_{dur} / 1$ year) occur, while for transients on the order of years to millennia, fewer than 50 ($t_{dur}/1$ year)$^2$ occur.Comment: Accepted for publication in A

Macrophage reprogramming for therapy.

Funder: MRC UK Dementia Research Institute ProfessorshipDysfunction of the immune system underlies a plethora of human diseases, requiring the development of immunomodulatory therapeutic intervention. To date, most strategies employed have been focusing on the modification of T lymphocytes, and although remarkable improvement has been obtained, results often fall short of the intended outcome. Recent cutting-edge technologies have highlighted macrophages as potential targets for disease control. Macrophages play central roles in development, homeostasis and host defence, and their dysfunction and dysregulation have been implicated in the onset and pathogenesis of multiple disorders including cancer, neurodegeneration, autoimmunity and metabolic diseases. Recent advancements have led to a greater understanding of macrophage origin, diversity and function, in both health and disease. Over the last few years, a variety of strategies targeting macrophages have been developed and these open new therapeutic opportunities. Here, we review the progress in macrophage reprogramming in various disorders and discuss the potential implications and challenges for macrophage-targeted approaches in human disease

Type i collagen cleavage is essential for effective fibrotic repair after myocardial infarction

Efficient deposition of type I collagen is fundamental to healing after myocardial infarction. Whether there is also a role for cleavage of type I collagen in infarct healing is unknown. To test this, we undertook coronary artery occlusion in mice with a targeted mutation (Col1a1 r/r) that yields collagenase-resistant type I collagen. Eleven days after infarction, Col1a1 r/r mice had a lower mean arterial pressure and peak left ventricular systolic pressure, reduced ventricular systolic function, and worse diastolic function, compared with wild-type littermates. Infarcted Col1a1 r/r mice also had greater 30-day mortality, larger left ventricular lumens, and thinner infarct walls. Interestingly, the collagen fibril content within infarcts of mutant mice was not increased. However, circular polarization microscopy revealed impaired collagen fibril organization and mechanical testing indicated a predisposition to scar microdisruption. Three-dimensional lattices of collagenase-resistant fibrils underwent cell-mediated contraction, but the fibrils did not organize into birefringent collagen bundles. In addition, time-lapse microscopy revealed that, although cells migrated smoothly on wild-type collagen fibrils, crawling and repositioning on collagenase-resistant collagen was impaired. We conclude that type I collagen cleavage is required for efficient healing of myocardial infarcts and is critical for both dynamic positioning of collagen-producing cells and hierarchical assembly of collagen fibrils. This seemingly paradoxical requirement for collagen cleavage in fibrotic repair should be considered when designing potential strategies to inhibit matrix degradation in cardiac disease. © 2011 American Society for Investigative Pathology

Macrophage reprogramming for therapy

Dysfunction of the immune system underlies a plethora of human diseases, requiring the development of immunomodulatory therapeutic intervention. To date, most strategies employed have been focusing on the modification of T lymphocytes, and although remarkable improvement has been obtained, results often fall short of the intended outcome. Recent cutting‐edge technologies have highlighted macrophages as potential targets for disease control. Macrophages play central roles in development, homeostasis and host defence, and their dysfunction and dysregulation have been implicated in the onset and pathogenesis of multiple disorders including cancer, neurodegeneration, autoimmunity and metabolic diseases. Recent advancements have led to a greater understanding of macrophage origin, diversity and function, in both health and disease. Over the last few years, a variety of strategies targeting macrophages have been developed and these open new therapeutic opportunities. Here, we review the progress in macrophage reprogramming in various disorders and discuss the potential implications and challenges for macrophage‐targeted approaches in human disease

Tissue‐resident macrophages actively suppress IL‐1beta release via a reactive prostanoid/IL‐10 pathway

The alarm cytokine interleukin‐1β (IL‐1β) is a potent activator of the inflammatory cascade following pathogen recognition. IL‐1β production typically requires two signals: first, priming by recognition of pathogen‐associated molecular patterns leads to the production of immature pro‐IL‐1β; subsequently, inflammasome activation by a secondary signal allows cleavage and maturation of IL‐1β from its pro‐form. However, despite the important role of IL‐1β in controlling local and systemic inflammation, its overall regulation is still not fully understood. Here we demonstrate that peritoneal tissue‐resident macrophages use an active inhibitory pathway, to suppress IL‐1β processing, which can otherwise occur in the absence of a second signal. Programming by the transcription factor Gata6 controls the expression of prostacyclin synthase, which is required for prostacyclin production after lipopolysaccharide stimulation and optimal induction of IL‐10. In the absence of secondary signal, IL‐10 potently inhibits IL‐1β processing, providing a previously unrecognized control of IL‐1β in tissue‐resident macrophages