Levels of interpopulation differentiation among different functional classes of immunologically important genes

It has been postulated that gene function may influence the degree to which allele frequencies differ among populations. In order to evaluate this effect, genotypic data from resequencing studies of genes classified as cytokines, cytokine receptors, cell adhesion molecules, Toll-like receptors and coagulation proteins were analysed for genetic differentiation (FST) between population samples of European and African descent. FST values did not differ statistically among functional groups when all polymorphic sites were included in the analyses. However, analysis based on nonsynonymous SNPs alone suggested weak heterogeneity among functional classes (P=0.0424). Particularly high levels of differentiation were shown by individual nonsynonymous SNPs at some genes, most notably ICAM1 and some Toll-like receptors. These genes interact directly with pathogens, and may therefore have been subject to geographically localised natural selection. Such loci warrant particular attention in studies of genetic disease risk and local adaptation to environmental conditions.     

A qualitative process evaluation using the behaviour change wheel approach: Did a whole genome sequence report form (SRF) used to reduce nosocomial SARS-CoV-2 within UK hospitals operate as anticipated?

Purpose

The aim of this study was to conduct a process evaluation of a whole-genome sequence report form (SRF) used to reduce nosocomial SARS-CoV-2 through changing infection prevention and control (IPC) behaviours within the COVID-19 pandemic.

Methods

We used a three-staged design. Firstly, we described and theorized the purported content of the SRF using the behaviour change wheel (BCW). Secondly, we used inductive thematic analysis of one-to-one interviews (n = 39) to explore contextual accounts of using the SRF. Thirdly, further deductive analysis gauged support for the intervention working as earlier anticipated.

Results

It was possible to theorize the SRF using the BCW approach and visualize it within a simple logic model. Inductive thematic analyses identified the SRF's acceptability, ease of use and perceived effectiveness. However, major challenges to embedding it in routine practice during the unfolding COVID-19 crisis were reported. Notwithstanding this insight, deductive analysis showed support for the putative intervention functions ‘Education’, ‘Persuasion’ and ‘Enablement’; behaviour change techniques ‘1.2 Problem solving’, ‘2.6 Biofeedback’, ‘2.7 Feedback on outcomes of behaviour’ and ‘7.1 Prompts and cues’; and theoretical domains framework domains ‘Knowledge’ and ‘Behavioural regulation’.

Conclusions

Our process evaluation of the SRF, using the BCW approach to describe and theorize its content, provided granular support for the SRF working to change IPC behaviours as anticipated. However, our complementary inductive thematic analysis highlighted the importance of the local context in constraining its routine use. For SRFs to reach their full potential in reducing nosocomial infections, further implementation research is needed.     

The cyclopean eye is relevant for predicting visual direction

Wells-Hering's laws summarize how we process direction and predict that monocular stimuli appear displaced with respect to the viewer, but not with respect to other seen objects [Erkelens, C. J., & van Ee, R. (2002). The role of the cyclopean eye in vision: sometimes inappropriate, always irrelevant. Vision Research 42, 1157-1163] criticized this view and claimed that there is no perceptual displacement of these stimuli. We challenge their claim and improve on shortcomings of past studies. LEDs were monocularly presented to the observers, without their knowledge of which eye was being stimulated. Viewing distance was 9-10 cm; fixation distance was 30 cm. Observers reported the perceived relative and absolute directions of monocular stimuli. Our results are consistent with Wells-Hering's laws.     

Expression of protease activated receptor-2 (PAR-2) in central airways of smokers and non-smokers

BACKGROUND: Protease activated receptor-2 (PAR-2) is a transmembrane G protein coupled receptor preferentially activated by trypsin and tryptase. The protease activated receptors play an important role in most components of injury responses including cell proliferation, migration, matrix remodelling, and inflammation. Cigarette smoking causes an inflammatory process in the central airways, peripheral airways, lung parenchyma, and adventitia of pulmonary arteries. METHODS: To quantify the expression of PAR-2 in the central airways of smokers and non-smokers, surgical specimens obtained from 30 subjects undergoing lung resection for localised pulmonary lesions (24 with a history of cigarette smoking and six non-smoking control subjects) were examined. Central airways were immunostained with an antiserum specific for PAR-2 and PAR-2 expression was quantified using light microscopy and image analysis. RESULTS: PAR-2 expression was found in bronchial smooth muscle, epithelium, glands, and in the endothelium and smooth muscle of bronchial vessels. PAR-2 expression was similar in the central airways of smokers and non-smokers. When smokers were divided according to the presence of symptoms of chronic bronchitis and chronic airflow limitation, PAR-2 expression was increased in smooth muscle (median 3.8 (interquartile range 2.9-5.8) and 1.4 (1.07-3.4) respectively); glands (33.3 (18.2-43.8) and 16.2 (11.5-22.2), respectively); and bronchial vessels (54.2 (48.7-56.8) and 40.0 (36-40.4), respectively) of smokers with symptoms of chronic bronchitis with normal lung function compared with smokers with chronic airflow limitation (COPD), but the increase was statistically significant (p<0.005) only for bronchial vessels. CONCLUSIONS: PAR-2 is present in bronchial smooth muscle, glands, and bronchial vessels of both smokers and non-smokers. An increased expression of PAR-2 was found in bronchial vessels of patients with bronchitis compared with those with COPD.     

The cyclopean eye in vision: the new and old data continue to hit you right between the eyes

We argue against recent claims by Erkelens and van Ee (Vision Res., in press) and by Erkelens (Vision Res. 40 (2000) 2411) that "the concept of the cyclopean eye is em leader always irrelevant as far as vision is concerned" (p. 1157) [corrected] and that "perceived direction during monocular viewing is based on the signals of the viewing eye only" (p. 2411), respectively. In Experiment 1, we presented a pair of small lights on a visual axis and measured the absolute visual direction of the near light with reference to different parts of the face. The near light appeared in front of the bridge of the nose or very near it, contrary to what was expected from Erkelens and van Ee's claim that monocular stimuli are seen in their correct locations. In Experiment 2, we replicated Erkelens' experiments with measurements of phoria and analyses of eye movements. The results confirmed his finding that the cyclopean illusion occurred rarely in the monocular condition, but our phoria and eye movement data provided the basis for a very different interpretation. Our data show that the oculomotor signal in his particular monocular condition was considerably weaker than in his binocular condition; therefore, the rarity of the monocular cyclopean illusion is not surprising. Moreover, since both claims above are based on an over-generalization of the results of Erkelens' study, neither claim is persuasive.     

Integrin expression on neutrophils and mononuclear cells in blood and induced sputum in stable asthma

BACKGROUND: We speculated that the expression of integrins in the airway lumen of asthmatic subjects might be altered compared with normal subjects during cell recruitment from circulation. METHODS: To test this hypothesis, we investigated the expression of integrin alpha-chains (CD11a, CD11b, and CD11c) in hypertonic saline-induced sputum and peripheral blood leukocytes in mild to moderate stable asthmatic and control subjects. Immunoreactivity for integrin alpha-chains was assessed by immunocytology on cytospin preparations of sputum and blood. RESULTS: In comparison of the percentages of CD11a+, CD11b+ and CD11c+ mononuclear cells in sputum with their blood counterparts, no significant differences were observed in control subjects, whereas CD11a and CD11b in asthmatic subjects were less expressed on sputum cells. In both control and asthmatic subjects, sputum neutrophils tended to decrease their expression of integrin alpha-chains compared with circulating neutrophils. CONCLUSIONS: We showed that the sputum of asthmatics, unlike normal subjects, is characterized by decreased expression of integrins on mononuclear cells compared with their blood counterparts. The results suggest that downregulation of integrins occurs in asthmatic airways after cell recruitment from circulation.     

Lack of association of HLA class I genes and TNF alpha-308 polymorphism in toluene diisocyanate-induced asthma

BACKGROUND: Toluene diisocyanate (TDI)-induced asthma is a common cause of occupational asthma and it affects 5-15% of the exposed population suggesting an underlying genetic susceptibility. METHODS: To investigate the role of genetic factors in the development of TDI-induced asthma, we analyzed the distribution of human leukocyte antigen (HLA) class I genes and of tumor necrosis factor (TNF)-alpha A-308G polymorphism in 142 patients with TDI-induced asthma and in 50 asymptomatic exposed subjects. RESULTS: Neither the distribution of HLA class I antigens nor the distribution of TNF-alpha A-308G polymorphism was different between patients with TDI-induced asthma and asymptomatic exposed subjects. CONCLUSIONS: These results suggest that HLA class I antigens and TNF-alpha A-308G are not associated with susceptibility or resistance to the development of TDI-induced asthma.     

Expression of IFN-gamma-inducible protein; monocyte chemotactic proteins 1, 3, and 4; and eotaxin in TH1- and TH2-mediated lung diseases

BACKGROUND: Chemokines are involved in the influx of leukocytes into the airways in inflammatory lung diseases. The differential cell recruitment characteristic of T(H)1 versus T(H)2 immune responses may be associated with differential chemokine expression. OBJECTIVE: We investigated the expression of chemokines; monocyte chemotactic proteins (MCPs) 1, 3, and 4; eotaxin; and IFN-gamma-inducible protein 10 (IP-10) in both T(H)1- and T(H)2-mediated lung diseases. METHODS: By using immunocytochemistry and in situ hybridization, we examined the protein and mRNA expression, respectively, in bronchoalveolar lavage and biopsy samples in subjects with asthma, tuberculosis, sarcoidosis, and chronic bronchitis. RESULTS: Increased immunoreactivity and mRNA expression of IP-10 and of the MCPs was found in the bronchoalveolar lavage fluid and biopsy specimens of subjects with asthma and tuberculosis compared with that of control subjects (P <.005). IP-10, however, was particularly increased in subjects with sarcoidosis (P <.001). Eotaxin, on the other hand, was increased only in patients with asthma when compared with control subjects (P <.005). CONCLUSION: This study demonstrates that MCP-1, MCP-3, and MCP-4 expression is not specifically associated with lung diseases characterized by a particular cytokine profile. In contrast, IP-10 is mostly expressed in T(H)1-mediated diseases, and eotaxin expression seems to be specifically associated with lung diseases of a T(H)2 cytokine profile.     

The transcription factors hypoxia‐inducible factor 1α and Ets‐1 colocalize in the hypoxic synovium of inflamed joints in adjuvant‐induced arthritis

Objective

To determine the relationship between hypoxia and the expression of Ets‐1 and hypoxia‐inducible factor 1α (HIF‐1α) in both normal and inflamed joints. Adjuvant‐induced arthritis (AIA) was used as the model system, since it mirrors many aspects of the pathology of rheumatoid arthritis.

Methods

Adjuvant arthritis was induced in a group of 10 female Lewis rats. A second group of 10 uninjected female Lewis rats served as naive controls. When a maximum clinical joint score was achieved in the AIA group, all 20 rats were injected with the specific hypoxic cell marker Hypoxyprobe‐1 and subsequently killed. Hypoxyprobe‐1 adducts, Ets‐1, and HIF‐1α were localized in the joints of the hind feet from these groups using immunohistochemistry.

Results

Compared with the joints from control rats, inflamed joints contained markedly more cells with Hypoxyprobe‐1 adduct immunoreactivity, Ets‐1–immunoreactive nuclei, and nuclear immunoreactivity for both Ets‐1 and HIF‐1α.

Conclusion

Our results demonstrate the presence of hypoxia in inflamed joints in this experimental model of arthritis. The colocalization of Ets‐1 and HIF‐1α in these hypoxic areas suggests that hypoxia may induce Ets‐1 and HIF‐1α expression during joint inflammation.