We investigated the impact of season relative to other determinants of chronic obstructive pulmonary disease (COPD) exacerbation frequency in a long-term international study of patients with forced ...expiratory volume in 1 s (FEV(1)) <60% predicted. COPD exacerbations were defined by worsening symptoms requiring systemic corticosteroids and/or antibiotics (moderate) or hospital admission (severe). Seasonality effect was calculated as the proportion of patients experiencing an exacerbation each month. Exacerbations in the northern and southern regions showed an almost two-fold increase in the winter months. No seasonal pattern occurred in the tropics. Overall, 38% of exacerbations were treated with antibiotics only, 19% with systemic corticosteroids only and 43% with both, while 20% required hospital admission irrespective of the season. Exacerbation frequency was associated with older age, lower body mass index, lower FEV(1) % pred and history of prior exacerbations. Females and patients with worse baseline breathlessness, assessed using the Medical Research Council (MRC) dyspnoea scale, exacerbated more often (rate ratio (RR) for male versus female 0.7, 95% CI 0.7-0.8 (p<0.001); RR for MRC dyspnoea score 3 versus 1 and 2 combined 1.1, 95% CI 1.1-1.2 (p<0.001)). The effect of season was independent of these risk factors. COPD exacerbations and hospitalisations were more frequent in winter.
Recently, we reported that vimentin-type intermediate filaments, in addition to microfilaments, associate with alphavbeta3 integrin-positive focal contacts in endothelial cells. To gain insight into ...intermediate filament-focal contact interaction, we induced expression of yellow fluorescent protein (YFP)-integrin beta3 and cyan fluorescent protein (CFP)-vimentin protein in endothelial cells. At least 50% of the YFP-beta3 integrin-labeled focal contacts associated with CFP-labeled vimentin intermediate filaments in live cells. Moreover, focal contacts and intermediate filaments moved in concert in the plane of the membrane and assembling focal contacts were sites of vimentin filament assembly. When endothelial cells were subjected to flow, large focal contacts assembled and associated with thick vimentin bundles. These large focal contacts showed minimal dynamic activity. Cells in which vimentin expression had been inhibited by RNA interference assembled smaller than normal focal contacts. More dramatically, such cells showed decreased adhesion to the substratum. These data provide evidence that the vimentin cytoskeleton regulates focal contact size and helps stabilize cell-matrix adhesions in endothelial cells.
To determine whether functional connectivity is altered in subjects with mutations in the microtubule associated protein tau (MAPT) gene who were asymptomatic but were destined to develop dementia, ...and to compare these findings to those in subjects with behavioral variant frontotemporal dementia (bvFTD).
In this case-control study, we identified 8 asymptomatic subjects with mutations in MAPT and 8 controls who screened negative for mutations in MAPT. Twenty-one subjects with a clinical diagnosis of bvFTD were also identified and matched to 21 controls. All subjects had resting-state fMRI. In-phase functional connectivity was assessed between a precuneus seed in the default mode network (DMN) and a fronto-insular cortex seed in the salience network, and the rest of the brain. Atlas-based parcellation was used to assess functional connectivity and gray matter volume across specific regions of interest.
The asymptomatic MAPT subjects and subjects with bvFTD showed altered functional connectivity in the DMN, with reduced in-phase connectivity in lateral temporal lobes and medial prefrontal cortex, compared to controls. Increased in-phase connectivity was also observed in both groups in the medial parietal lobe. Only the bvFTD group showed altered functional connectivity in the salience network, with reduced connectivity in the fronto-insular cortex and anterior cingulate. Gray matter loss was observed across temporal, frontal, and parietal regions in bvFTD, but not in the asymptomatic MAPT subjects.
Functional connectivity in the DMN is altered in MAPT subjects before the occurrence of both atrophy and clinical symptoms, suggesting that changes in functional connectivity are early features of the disease.
The Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) is an eight-item questionnaire designed to assess and quantify the impact of COPD symptoms on health status. COPD exacerbations ...impair quality of life and are characterized by worsening respiratory symptoms from the stable state. We hypothesized that CAT scores at exacerbation relate to exacerbation severity as measured by exacerbation duration, lung function impairment, and systemic inflammation.
To evaluate the usefulness of the CAT to assess exacerbation severity.
One hundred sixty-one patients enrolled in the London COPD cohort completed the CAT at baseline (stable state), exacerbation, and during recovery between April 2010 and June 2011.
Frequent exacerbators had significantly higher baseline CAT scores than infrequent exacerbators (19.5 ± 6.6 vs. 16.8 ± 8.0, P = 0.025). In 152 exacerbations, CAT scores rose from an average baseline value of 19.4 ± 6.8 to 24.1 ± 7.3 (P < 0.001) at exacerbation. Change in CAT score from baseline to exacerbation onset was significantly but weakly related to change in C-reactive protein (rho = 0.26, P = 0.008) but not to change in fibrinogen (rho = 0.09, P = 0.351) from baseline to exacerbation. At exacerbation, rises in CAT score were significantly associated with falls in FEV(1) (rho = -0.20, P = 0.032). Median recovery time as judged by symptom diary cards was significantly related to the time taken for the CAT score to return to baseline (rho = 0.42, P = 0.012).
The CAT provides a reliable score of exacerbation severity. Baseline CAT scores are elevated in frequent exacerbators. CAT scores increase at exacerbation and reflect severity as determined by lung function and exacerbation duration.
We present first results of the H2O Southern Galactic Plane Survey (HOPS), using the Mopra Radio Telescope with a broad-band backend and a beam size of about 2 arcmin. We have observed 100 deg2 of ...the southern Galactic plane at 12 mm (19.5-27.5 GHz), including spectral line emission from H2O masers, multiple metastable transitions of ammonia, cyanoacetylene, methanol and radio recombination lines. In this paper, we report on the characteristics of the survey and H2O maser emission. We find 540 H2O masers, of which 334 are new detections. The strongest maser is 3933 Jy and the weakest is 0.7 Jy, with 62 masers over 100 Jy. In 14 maser sites, the spread in the velocity of the H2O maser emission exceeds 100 km s−1. In one region, the H2O maser velocities are separated by 351.3 km s−1. The rms noise levels are typically between 1 and 2 Jy, with 95 per cent of the survey under 2 Jy. We estimate completeness limits of 98 per cent at around 8.4 Jy and 50 per cent at around 5.5 Jy. We estimate that there are between 800 and 1500 H2O masers in the Galaxy that are detectable in a survey with similar completeness limits to HOPS. We report possible masers in NH3 (11,9) and (8,6) emission towards G19.61−0.23 and in the NH3 (3,3) line towards G23.33−0.30.
Abstract The outer most layer of the skin, the epidermis, is attached to the dermis via a sheet of extracellular matrix proteins termed the basement membrane zone (BMZ). In the intact skin, adhesion ...of the keratinocytes in the basal layer of the epidermis to the BMZ is facilitated primarily by hemidesmosomes which associate with the keratin cytoskeleton. Cultured keratinocytes do not assemble bona fide hemidesmosomes although hemidesmosome protein clusters (stable anchoring contacts) are found along the substrate-attached surface of the cells and towards the leading edge of keratinocytes repopulating scratch wounds. Actin cytoskeleton-associated matrix adhesion devices termed focal contacts are not thought to play an important role in the adhesion of keratinocytes to the BMZ in intact skin but are prominent in cultured keratinocytes where they are believed to regulate cell migration. We review the molecular components, functions, dynamics and cross-talk of hemidesmosomes and focal contacts in keratinocytes. In addition, we briefly describe what is known about their role in autoimmune and genetic blistering diseases of the skin. We also discuss recent publications which indicate, contrary to expectation, that certain focal contact proteins retard keratinocyte migration while hemidesmosomal proteins regulate directed keratinocyte motility during wound healing.
We explore the origin of mid-infrared (mid-IR) dust extinction in all 20 nearby (z < 0.05) bona fide Compton-thick (N sub(H) > 1.5 x 10 super(24) cm super(-2)) active galactic nuclei (AGNs) with hard ...energy (E > 10 keV) X-ray spectral measurements. We accurately measure the silicate absorption features at lambda ~ 9.7 mu m in archival low-resolution (R ~ 57-127) Spitzer Infrared Spectrograph spectroscopy, and show that only a minority (approx =45%) of nearby Compton-thick AGNs have strong Si-absorption features (S sub(9.7) = ln (functionof sub(int)/functionof sub(obs)) > ~0.5) which would indicate significant dust attenuation. The majority (approx =60%) are star formation dominated (AGN:SB < 0.5) at mid-IR wavelengths and lack the spectral signatures of AGN activity at optical wavelengths, most likely because the AGN emission lines are optically extinguished. Those Compton-thick AGNs hosted in low-inclination-angle galaxies exhibit a narrow range in Si-absorption (S sub(9.7) ~ 0-0.3), which is consistent with that predicted by clumpy-torus models. However, on the basis of the IR spectra and additional lines of evidence, we conclude that the dominant contribution to the observed mid-IR dust extinction is dust located in the host galaxy (i.e., due to disturbed morphologies, dust lanes, galaxy inclination angles) and not necessarily a compact obscuring torus surrounding the central engine.
Animal displays are often perceived by intended and unintended receivers in more than one sensory system. In addition, cues that are an incidental consequence of signal production can also be ...perceived by different receivers, even when the receivers use different sensory systems to perceive them. Here we show that the vocal responses of male túngara frogs (Physalaemus pustulosus) increase twofold when call-induced water ripples are added to the acoustic component of a rival's call. Hunting bats (Trachops cirrhosus) can echolocate this signal by-product and prefer to attack model frogs when ripples are added to the acoustic component of the call. This study illustrates how the perception of a signal by-product by intended and unintended receivers through different sensory systems generates both costs and benefits for the signaler.
The diseases caused by thrips-transmitted tospoviruses (genus
Tospovirus, family
Bunyaviridae) are a major constraint to production of important vegetable, legume and ornamental crops in different ...parts of the world. Tospoviruses are characterized by having tripartite RNA genomes and utilizing both negative and ambisense genome expression strategies. Their often wide and overlapping host ranges, emergence of resistance-breaking strains, circulative and propagative relationship with polyphagous thrips vectors, and difficulties in predicting their outbreaks pose challenges to development and implementation of effective management programmes. Despite these challenges, for a few tospoviruses, considerable progress has been made in successful development and deployment of practical and effective integrated disease management programmes. This has been due to increased understanding of their molecular biology, plant-virus and virus-vector interactions and epidemiology, and to identification of risk factors that contribute to increased disease incidence and of tactics to mitigate those risk factors. However, challenges remain as resistance-breaking or other new strains of known tospoviruses and completely new tospovirus species continue to be described from various parts of the world and have the potential to cause damaging epidemics. To protect crops from the losses caused by severe tospovirus outbreaks, continued vigilance is required to identify and characterize these emerging tospoviruses, determine their impact on crop production, understand their epidemiologies and develop, evaluate and implement control measures to reduce their impact on crop production.
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