AIM:To develop a model of stress-induced senescence to study the hepatocyte senescence associated secretory phenotype(SASP).METHODS:Hydrogen peroxide treatment was used to induce senescence in the ...human Hep G2 hepatocyte cell line.Senescence was confirmed by cytochemical staining for a panel of markers including Ki67,p21,heterochromatin protein 1β,and senescence-associated-β-galactosidase activity.Senescent hepatocytes were characterised by gene expression arrays and quantitative polymerase chain reaction(q PCR),and conditioned media was used in proteomic analyses,a human chemokine protein array,and cell migration assays to characterise the composition and function of the hepatocyte SASP.RESULTS:Senescent hepatocytes induced classical markers of senescence(p21,heterochromatin protein1β,and senescence-associated-β-galactosidase activity);and downregulated the proliferation marker,Ki67.Hepatocyte senescence induced a 4.6-fold increase in total secreted protein(P=0.06)without major alterations in the protein profile.Senescence-induced genes were identified by microarray(Benjamini Hochbergcorrected P<0.05);and,consistent with the increase in secreted protein,gene ontology analysis revealed a significant enrichment of secreted proteins among inducible genes.The hepatocyte SASP included characteristic factors such as interleukin(IL)-8 and IL-6,as well as novel components such as SAA4,IL-32and Fibrinogen,which were validated by q PCR and/or chemokine protein array.Senescent hepatocyteconditioned medium elicited migration of inflammatory(granulocyte-macrophage colony stimulating factor,GM-CSF-derived),but not non-inflammatory(CSF-1-derived)human macrophages(P=0.022),which could contribute to a pro-inflammatory microenvironment in vivo,or facilitate the clearance of senescent cells.CONCLUSION:Our novel model of hepatocyte senescence provides insights into mechanisms by which senescent hepatocytes may promote chronic liver disease pathogenesis.
The relationship between adjunctive behaviour, in the form of schedule-induced drinking, and escape-avoidance behaviour was investigated, using rats as subjects. Escape-avoidance behaviour consisted ...of vacating the site of intermittent food delivery and then staying away from the food site. Independent groups were run on fixed-time schedules ranging from 30 seconds to 240 seconds. Groups were run either in a small chamber that prevented movement away from the food site or in a large chamber that allowed considerable movement away from the food site. Each group was exposed to two types of chamber wall stimuli. Chamber wall stimuli either were the same throughout or were different in a section away from the food site. In both chambers the drinking site was adjacent to the food site. Drinking was reliably induced on all schedules except the longest one. Interval size had a marked effect on drinking, but chamber size and chamber wall stimuli did not. In the large chamber more escape-avoidance occurred when wall stimuli were different. Escape-avoidance was also a direct function of interval length when wall stimuli were different. When most drinking was confined to a portion of the interval, drinking preceded escape-avoidance. The results did not support Staddon and Simmelhag's (1971) and Falk's (1977) suggestions that escape from the site of scheduled incentives is implicated in adjunctive behaviour. Escape-avoidance behaviour was not a substitute for schedule-induced drinking. Instead, escape-avoidance behaviour appeared to be a facultative behaviour. It was suggested that both adjunctive behaviours and escape-avoidance behaviour may be stress-related, and that adjunctive behaviours are associated with arousal induced by schedules while escape-avoidance is associated with schedule aversiveness.
Defects caused by tumour excision in the floor of the mouth can be closed by different methods. We present thirteen cases treated in our department over the last seven years in whom naso-labial flaps ...were used. Twelve patients had squamous cell carcinoma of the floor of the mouth and one had fibro-sarcoma of the right lower mandible. Five received post-operative radiotherapy, one was resected following radiotherapy and seven were treated with surgery alone. Patient selection is important to give good functional results without compromising tumour clearance.
How antigen valency affects B cells in vivo during immune responses is not well understood. Here, using HIV immunogens with defined valencies ranging from 1 to 60, we investigated the role of antigen ...valency during different phases of B cell responses in vivo. Highly multimerized immunogens preferentially rapidly activated cognate B cells, with little affinity discrimination. This led to strong early induction of the transcription factors IRF4 (interferon regulatory factor 4) and Bcl6, driving both early extrafollicular plasma cell and germinal center responses, in a CD4+ T-cell-dependent manner, involving B cells with a broad range of affinities. Low-valency antigens induced smaller effector B cell responses, with preferential recruitment of high-affinity B cells. Thus, antigen valency has multifaceted effects on B cell responses and can dictate affinity thresholds and competitive landscapes for B cells in vivo, with implications for vaccine design.
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•Antigen valency dictates the magnitude and composition of B cell responses•High valency enables robust activation and effector differentiation of B cells•Antigen valency alters breadth of B cell affinities recruited
Detailed mechanistic understanding of how differing antigen valencies influence cognate B cells in vivo is lacking. Kato et al. show antigen valency dictates the breadth of affinity range of B cells that are recruited and the ability of cognate B cells to differentiate into effector cells. This had profound impacts on the magnitude of germinal center and extrafollicular plasmablast responses. The study also highlights the need to carefully consider valency in vaccine design.
POLYTHERMAL GLACIER HYDROLOGY: A REVIEW Irvine-Fynn, Tristram D. L.; Hodson, Andrew J.; Moorman, Brian J. ...
Reviews of geophysics,
December 2011, Volume:
49, Issue:
4
Journal Article
Peer reviewed
Open access
The manner by which meltwater drains through a glacier is critical to ice dynamics, runoff characteristics, and water quality. However, much of the contemporary knowledge relating to glacier ...hydrology has been based upon, and conditioned by, understanding gleaned from temperate valley glaciers. Globally, a significant proportion of glaciers and ice sheets exhibit nontemperate thermal regimes. The recent, growing concern over the future response of polar glaciers and ice sheets to forecasts of a warming climate and lengthening summer melt season necessitates recognition of the hydrological processes in these nontemperate ice masses. It is therefore timely to present an accessible review of the scientific progress in glacial hydrology where nontemperate conditions are dominant. This review provides an appraisal of the glaciological literature from nontemperate glaciers, examining supraglacial, englacial, and subglacial environments in sequence and their role in hydrological processes within glacierized catchments. In particular, the variability and complexity in glacier thermal regimes are discussed, illustrating how a unified model of drainage architecture is likely to remain elusive due to structural controls on the presence of water. Cold ice near glacier surfaces may reduce meltwater flux into the glacier interior, but observations suggest that the transient thermal layer of near surface ice holds a hydrological role as a depth‐limited aquifer. Englacial flowpaths may arise from the deep incision of supraglacial streams or the propagation of hydrofractures, forms which are readily able to handle varied meltwater discharge or act as locations for water storage, and result in spatially discrete delivery of water to the subglacial environment. The influence of such drainage routes on seasonal meltwater release is explored, with reference to summer season upwellings and winter icing formation. Moreover, clear analogies emerge between nontemperate valley glacier and ice sheet hydrology, the discussion of which indicates how persistent reassessment of our conceptualization of glacier drainage systems is required. There is a clear emphasis that continued, integrated endeavors focused on process glaciology at nontemperate glaciers are a scientific imperative to augmenting the existing body of research centered on ice mass hydrology.
Key Points
Site specificity of nontemperate glacier hydrology is linked to thermal regime
Analogies exist between the hydrology of ice sheets and nontemperate valley glaciers
Continued investigations of meltwater flowpaths will improve current understanding
In Methyl Ammonium Lead Iodide (MAPI) perovskite solar cells, screening of the built-in field by mobile ions has been proposed as part of the cause of the large hysteresis observed in the ...current/voltage scans in many cells. We show that photocurrent transients measured immediately ( e.g. 100 μs) after a voltage step can provide direct evidence that this field screening exists. Just after a step to forward bias, the photocurrent transients are reversed in sign ( i.e. inverted), and the magnitude of the inverted transients can be used to find an upper bound on the width of the space charge layers adjacent to the electrodes. This in turn provides a lower bound on the mobile charge concentration, which we find to be ≳1 × 10 17 cm −3 . Using a new photocurrent transient experiment, we show that the space charge layer thickness remains approximately constant as a function of bias, as expected for mobile ions in a solid electrolyte. We also discuss additional characteristics of the inverted photocurrent transients that imply either an unusually stable deep trapping, or a photo effect on the mobile ion conductivity.
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