The Chicken Yolk Sac IgY Receptor, a Mammalian Mannose Receptor Family Member, Transcytoses IgY across Polarized Epithelial Cells

In mammals the transfer of passive immunity from mother to young is mediated by the MHC-related receptor FcRn, which transports maternal IgG across epithelial cell barriers. In birds, maternal IgY in egg yolk is transferred across the yolk sac to passively immunize chicks during gestation and early independent life. The chicken yolk sac IgY receptor (FcRY) is the ortholog of the mammalian phospholipase A2 receptor, a mannose receptor family member, rather than an FcRn or MHC homolog. FcRn and FcRY both exhibit ligand binding at the acidic pH of endosomes and ligand release at the slightly basic pH of blood. Here we show that FcRY expressed in polarized mammalian epithelial cells functioned in endocytosis, bidirectional transcytosis, and recycling of chicken FcY/IgY. Confocal immunofluorescence studies demonstrated that IgY binding and endocytosis occurred at acidic but not basic pH, mimicking pH-dependent uptake of IgG by FcRn. Colocalization studies showed FcRY-mediated internalization via clathrin-coated pits and transport involving early and recycling endosomes. Disruption of microtubules partially inhibited apical-to-basolateral and basolateral-to-apical transcytosis, but not recycling, suggesting the use of different trafficking machinery. Our results represent the first cell biological evidence of functional equivalence between FcRY and FcRn and provide an intriguing example of how evolution can give rise to systems in which similar biological requirements in different species are satisfied utilizing distinct protein folds

Planet Hunters. VIII. Characterization of 41 Long-Period Exoplanet Candidates from Kepler Archival Data

The census of exoplanets is incomplete for orbital distances larger than 1 AU. Here, we present 41 long-period planet candidates in 38 systems identified by Planet Hunters based on Kepler archival data (Q0-Q17). Among them, 17 exhibit only one transit, 14 have two visible transits and 10 have more than three visible transits. For planet candidates with only one visible transit, we estimate their orbital periods based on transit duration and host star properties. The majority of the planet candidates in this work (75%) have orbital periods that correspond to distances of 1-3 AU from their host stars. We conduct follow-up imaging and spectroscopic observations to validate and characterize planet host stars. In total, we obtain adaptive optics images for 33 stars to search for possible blending sources. Six stars have stellar companions within 4". We obtain high-resolution spectra for 6 stars to determine their physical properties. Stellar properties for other stars are obtained from the NASA Exoplanet Archive and the Kepler Stellar Catalog by Huber et al. (2014). We validate 7 planet candidates that have planet confidence over 0.997 (3-{\sigma} level). These validated planets include 3 single-transit planets (KIC-3558849b, KIC-5951458b, and KIC-8540376c), 3 planets with double transits (KIC-8540376b, KIC-9663113b, and KIC-10525077b), and 1 planet with 4 transits (KIC-5437945b). This work provides assessment regarding the existence of planets at wide separations and the associated false positive rate for transiting observation (17%-33%). More than half of the long-period planets with at least three transits in this paper exhibit transit timing variations up to 41 hours, which suggest additional components that dynamically interact with the transiting planet candidates. The nature of these components can be determined by follow-up radial velocity and transit observations.Comment: Published on ApJ, 815, 127 Notations of validated planets are changed in accordance with naming convention of NASA Exoplanet Archiv

Carotid artery stenosis, an underestimated cause of stroke recurrence in patients with ischaemic monocular visual loss

INTRODUCTION Isolated monocular ischaemic events are thought to be low risk for stroke recurrence. In the presence of carotid stenosis however, the risks should not be treated similarly and surgical intervention should be considered at an early stage. The aim of this study was to determine the vascular risk profile and stroke recurrence in patients with ischaemic monocular visual loss. METHODS AND METHODS Consecutive records for all patients with monocular ischaemia were reviewed from January 2014 to October 2016. Stroke, transient ischaemic attack or monocular ischaemia recurrence within 90 days were recorded. Carotid stenosis was assessed with duplex ultrasound, computed tomography or magnetic resonance angiography. RESULTS In total, 400 patients presented with monocular ischaemia; 391 had carotid imaging (97.8%). Causality was symptomatic carotid stenosis ≥ 50% in 53 (13.6%), including carotid stenosis ≥ 70% in 31 (7.9%). Patients with permanent visual loss (n = 131) were more likely to have significant stenosis compared with patients with transient visual loss (n = 260), 19.8% compared with 10.4% (P = 0.012). Recurrent stroke, transient ischaemic attack or monocular ischaemia within 90 days after presentation occurred in three patients (5.7%) in the carotid stenosis group, compared to three (0.9%) who did not have stenosis (P = 0.035). Age, male sex and hypertension were associated with carotid stenosis but hypercholesterolaemia, diabetes and smoking were not. CONCLUSIONS Carotid stenosis ≥ 50% is present in patients with ocular ischaemia in approximately 20% of those with persistent visual loss and in 10% with transient visual loss. Those with carotid stenosis have a higher risk of stroke recurrence and should be considered urgent surgical intervention as other forms of stroke

A new perspective in bio-refining : Levoglucosenone and cleaner lignin from waste biorefinery hydrolysis lignin by selective conversion of residual saccharides

An unexpected opportunity is reported to improve the sustainability of biorefineries whereby 8 wt% levoglucosenone (LGE) can be derived from unconverted saccharides in a lignin-rich biorefinery waste stream in a highly selective fashion (>90%). Additionally, in the process a purer lignin is obtained which can be used for further processing or materials applications. LGE is a valuable and versatile product with a plethora of applications

Novel IgG-degrading enzymes of the IgdE protease family link substrate specificity to host tropism of <i>Streptococcus</i> species

Recently we have discovered an IgG degrading enzyme of the endemic pig pathogen S. suis designated IgdE that is highly specific for porcine IgG. This protease is the founding member of a novel cysteine protease family assigned C113 in the MEROPS peptidase database. Bioinformatical analyses revealed putative members of the IgdE protease family in eight other Streptococcus species. The genes of the putative IgdE family proteases of S. agalactiae, S. porcinus, S. pseudoporcinus and S. equi subsp. zooepidemicus were cloned for production of recombinant protein into expression vectors. Recombinant proteins of all four IgdE family proteases were proteolytically active against IgG of the respective Streptococcus species hosts, but not against IgG from other tested species or other classes of immunoglobulins, thereby linking the substrate specificity to the known host tropism. The novel IgdE family proteases of S. agalactiae, S. pseudoporcinus and S. equi showed IgG subtype specificity, i.e. IgdE from S. agalactiae and S. pseudoporcinus cleaved human IgG1, while IgdE from S. equi was subtype specific for equine IgG7. Porcine IgG subtype specificities of the IgdE family proteases of S. porcinus and S. pseudoporcinus remain to be determined. Cleavage of porcine IgG by IgdE of S. pseudoporcinus is suggested to be an evolutionary remaining activity reflecting ancestry of the human pathogen to the porcine pathogen S. porcinus. The IgG subtype specificity of bacterial proteases indicates the special importance of these IgG subtypes in counteracting infection or colonization and opportunistic streptococci neutralize such antibodies through expression of IgdE family proteases as putative immune evasion factors. We suggest that IgdE family proteases might be valid vaccine targets against streptococci of both human and veterinary medical concerns and could also be of therapeutic as well as biotechnological use

FcRn-mediated antibody transport across epithelial cells revealed by electron tomography

The neonatal Fc receptor (FcRn) transports maternal IgG across epithelial barriers, thereby providing the fetus or newborn with humoral immunity before its immune system is fully functional. In newborn rats, FcRn transfers IgG from milk to blood by apical-to-basolateral transcytosis across intestinal epithelial cells. The pH difference between the apical (pH 6.0–6.5) and basolateral (pH 7.4) sides of intestinal epithelial cells facilitates the efficient unidirectional transport of IgG, because FcRn binds IgG at pH 6.0–6.5 but not at pH 7 or more. As milk passes through the neonatal intestine, maternal IgG is removed by FcRn-expressing cells in the proximal small intestine (duodenum and jejunum); remaining proteins are absorbed and degraded by FcRn-negative cells in the distal small intestine (ileum). Here we use electron tomography to make jejunal transcytosis visible directly in space and time, developing new labelling and detection methods to map individual nanogold-labelled Fc within transport vesicles and simultaneously to characterize these vesicles by immunolabelling. Combining electron tomography with a nonperturbing endocytic label allowed us to conclusively identify receptor-bound ligands, resolve interconnecting vesicles, determine whether a vesicle was microtubule-associated, and accurately trace FcRn-mediated transport of IgG. Our results present a complex picture in which Fc moves through networks of entangled tubular and irregular vesicles, only some of which are microtubule-associated, as it migrates to the basolateral surface. New features of transcytosis are elucidated, including transport involving multivesicular body inner vesicles/tubules and exocytosis through clathrin-coated pits. Markers for early, late and recycling endosomes each labelled vesicles in different and overlapping morphological classes, revealing spatial complexity in endo-lysosomal trafficking

Linkage Mapping of Stem Saccharification Digestibility in Rice

Rice is the staple food of almost half of the world population, and in excess 90% of it is grown and consumed in Asia, but the disposal of rice straw poses a problem for farmers, who often burn it in the fields, causing health and environmental problems. However, with increased focus on the development of sustainable biofuel production, rice straw has been recognized as a potential feedstock for non-food derived biofuel production. Currently, the commercial realization of rice as a biofuel feedstock is constrained by the high cost of industrial saccharification processes needed to release sugar for fermentation. This study is focused on the alteration of lignin content, and cell wall chemotypes and structures, and their effects on the saccharification potential of rice lignocellulosic biomass. A recombinant inbred lines (RILs) population derived from a cross between the lowland rice variety IR1552 and the upland rice variety Azucena with 271 molecular markers for quantitative trait SNP (QTS) analyses was used. After association analysis of 271 markers for saccharification potential, 1 locus and 4 pairs of epistatic loci were found to contribute to the enzymatic digestibility phenotype, and an inverse relationship between reducing sugar and lignin content in these recombinant inbred lines was identified. As a result of QTS analyses, several cell-wall associated candidate genes are proposed that may be useful for marker-assisted breeding and may aid breeders to produce potential high saccharification rice varieties

The neuropsychology needs of a hyper-acute stroke unit

BACKGROUND AND AIM: Guidelines recommend routine assessment and management of mood and cognition after stroke, but little is known about the value or feasibility of providing neuropsychology input during the hyper-acute period. We aimed to identify and describe the extent and nature of neuropsychological needs and to investigate the feasibility of providing direct neuropsychology input within a hyper-acute setting. METHODS: Over a 7-month period, Multidisciplinary Team (MDT) members of a central London Hyper-Acute Stroke Unit (HASU) identified stroke patients who they believed would benefit from neuropsychology input, and categorised the nature of neuropsychology intervention required. We examined the demographic and clinical characteristics of the patients identified and the type of intervention required. RESULTS: 23% of patients (101/448) were identified as requiring neuropsychology input. Patients deemed to require input were younger, more likely to be male and more functionally disabled than those not requiring input. Cognitive assessment was the main identified need (93%) followed by mood (29%) and family support (9%). 30% of patients required two types of intervention. During a pilot of neuropsychology provision, 17 patients were seen; 15 completed a full cognitive assessment. All patients assessed presented with cognitive impairment despite three being deemed cognitively intact (> standardised cut-off) using a cognitive screening tool. CONCLUSION: We showed that direct neuropsychology input on a HASU is necessary for complex and varied interventions involving cognition, mood and family support. Furthermore, input is feasible and useful in detecting cognitive impairment not revealed by screening instruments

Additional Queen Square (QS) screening items improve the test accuracy of the Montreal Cognitive Assessment (MoCA) after acute stroke

BACKGROUND The Montreal Cognitive Assessment (MoCA) is a popular cognitive screening tool used in stroke, but lacks sensitivity for detecting impairment in stroke-relevant domains of processing speed, non-verbal memory and executive functions. Our aim was to assess whether the test accuracy of the MoCA can be improved with additional tailored screening items targeting these three domains. METHODS We included 196 patients admitted to an acute stroke unit at the National Hospital for Neurology and Neurosurgery, Queen Square (QS), London. Participants completed the MoCA as well as a series of additional QS-screening items designed to assess speed of processing, non-verbal memory and executive functions. Performance on the MoCA and QS screening items was compared with performance on “gold standard” neuropsychological assessment. RESULTS In our sample, 22% of patients were classified as “cognitively intact” on the traditional MoCA alone (≥ 25). However, when tested on the QS-screening items, 40% of these patients failed on speed of processing, 56% failed on non-verbal memory and 26% failed on executive functions. Compared with neuropsychological assessment, the QS-screening items had good sensitivity (QS-Speed: 0.85; QS-Vis: 0.71; QS-EF: 0.73) and modest specificity (QS-Speed: 0.59; QS-Vis: 0.39; QS-EF: 0.54), regardless of stroke lateralisation. CONCLUSION Additional screening items detected impairments in speed of processing, non-verbal memory and executive functions over and above those captured using the standard MoCA. The use of these QS-screening items improves the detection of post-stroke cognitive deficits in domains not adequately covered by the standard MoCA