Fate of duplicated genes in polyploid wheat

Introdução: O vírus da hepatite B é um Hepadnavirívus, com tropismo para os hepatócitos. Em todo o mundo, estima-se a existência de 2 mil milhões de pessoas infectadas com o vírus entre as quais 350 milhões padecem de hepatite B crónica. Por ano morrem aproximadamente 600.000 pessoas devido a hepatite B aguda ou crónica. A resposta imuno mediada decorrente da lesão mantida do vírus nos hepatócitos conduz à formação de fibrose. O esclarecimento dos mecanismos moleculares e celulares que regulam o balanço entre a formação dos constituintes da matriz extracelular e a sua degradação permitem a compreensão do processo da fibrogénese. Esta pressupõe acumulação de matriz extracelular, com alteração dos seus constituintes quer qualitativamente quer quantitativamente. A fibrólise, é o processo de degragação da matriz extra celular e está dependente da actuação de metaloproteases. O desequilíbrio destes processos resulta na acumulação ou diminuição da fibrose. A fibrose hepática é um processo dinâmico e reversível, mas cirrose, último estádio da fibrose, considerada por muitos autores irreversível, pode também regredir desde que se verifique, a remoção do estímulo fibrótico, o vírus, no caso da hepatite B. A morbilidade e a mortalidade na hepatite B crónica, está relacionada com a persistência da replicação viral, evolução para cirrose e carcinoma hepatocelular. Objectivos: Revisão bibliográfica sobre os resultados obtidos de regressão da fibrose/cirrose em doentes com hepatite B crónica. A regressão da cirrose na Hepatite B 2010 5 Conclusões: Os agentes anti-virais disponíveis para o tratamento da hepatite B crónica apresentam capacidade de controlo da replicação do vírus. A supressão mantida é sinónimo de eficácia terapêutica e modificação natural do curso da doença. A regressão da cirrose na hepatite B crónica, observada em alguns casos, está associada a diminuição da incidência das suas complicaçõese deve constituir um objectivo terapêutico

In Vivo Human Left-to-Right Ventricular Differences in Rate Adaptation Transiently Increase Pro-Arrhythmic Risk following Rate Acceleration

Left-to-right ventricular (LV/RV) differences in repolarization have been implicated in lethal arrhythmias in animal models. Our goal is to quantify LV/RV differences in action potential duration (APD) and APD rate adaptation and their contribution to arrhythmogenic substrates in the in vivo human heart using combined in vivo and in silico studies. Electrograms were acquired from 10 LV and 10 RV endocardial sites in 15 patients with normal ventricles. APD and APD adaptation were measured during an increase in heart rate. Analysis of in vivo electrograms revealed longer APD in LV than RV (207.8±21.5 vs 196.7±20.1 ms; P<0.05), and slower APD adaptation in LV than RV (time constant τs = 47.0±14.3 vs 35.6±6.5 s; P<0.05). Following rate acceleration, LV/RV APD dispersion experienced an increase of up to 91% in 12 patients, showing a strong correlation (r2 = 0.90) with both initial dispersion and LV/RV difference in slow adaptation. Pro-arrhythmic implications of measured LV/RV functional differences were studied using in silico simulations. Results show that LV/RV APD and APD adaptation heterogeneities promote unidirectional block following rate acceleration, albeit being insufficient for establishment of reentry in normal hearts. However, in the presence of an ischemic region at the LV/RV junction, LV/RV heterogeneity in APD and APD rate adaptation promotes reentrant activity and its degeneration into fibrillatory activity. Our results suggest that LV/RV heterogeneities in APD adaptation cause a transient increase in APD dispersion in the human ventricles following rate acceleration, which promotes unidirectional block and wave-break at the LV/RV junction, and may potentiate the arrhythmogenic substrate, particularly in patients with ischemic heart disease

Investigating Biomarkers for USH2A Retinopathy Using Multimodal Retinal Imaging

Pathogenic mutations in USH2A are a leading cause of visual loss secondary to non-syndromic or Usher syndrome-associated retinitis pigmentosa (RP). With an increasing number of RP-targeted clinical trials in progress, we sought to evaluate the photoreceptor topography under-lying patterns of loss observed on clinical retinal imaging to guide surrogate endpoint selection in USH2A retinopathy. In this prospective cross-sectional study, twenty-five patients with molecularly confirmed USH2A-RP underwent fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy (AOSLO) retinal imaging. Analysis comprised measurement of FAF horizontal inner (IR) and outer (OR) hyperautofluorescent ring diameter; SD-OCT ellipsoid zone (EZ) and external limiting membrane (ELM) width, normalised EZ reflectance; AOSLO foveal cone density and intact macular photoreceptor mosaic (IMPM) diam-eter. Thirty-two eyes from 16 patients (mean age ± SD, 36.0 ± 14.2 years) with USH2A-associated Usher syndrome type 2 (n = 14) or non-syndromic RP (n = 2) met the inclusion criteria. Spatial align-ment was observed between IR-EZ and OR-ELM diameters/widths (p <0.001). The IMPM border occurred just lateral to EZ loss (p < 0.001), although sparser intact photoreceptor inner segments were detected until ELM disruption. EZ width and IR diameter displayed a biphasic relationship with cone density whereby slow cone loss occurred until retinal degeneration reached ~1350 µm from the fovea, beyond which greater reduction in cone density followed. Normalised EZ reflectance and cone density were significantly associated (p <0.001). As the strongest correlate of cone density (p < 0.001) and best-corrected visual acuity (p <0.001), EZ width is the most sensitive biomarker of structural and functional decline in USH2A retinopathy, rendering it a promising trial endpoint

Cellular imaging of inherited retinal diseases using adaptive optics

Adaptive optics (AO) is an insightful tool that has been increasingly applied to existing imaging systems for viewing the retina at a cellular level. By correcting for individual optical aberrations, AO offers an improvement in transverse resolution from 10-15 μm to ~2 μm, enabling assessment of individual retinal cell types. One of the settings in which its utility has been recognised is that of the inherited retinal diseases (IRDs), the genetic and clinical heterogeneity of which warrants better cellular characterisation. In this review, we provide a summary of the basic principles of AO, its integration into multiple retinal imaging modalities and its clinical applications, focusing primarily on IRDs. Furthermore, we present a comprehensive summary of AO-based cellular findings in IRDs according to their associated disease-causing genes

Effect of autonomic blocking agents on the respiratory-related oscillations of ventricular action potential duration in humans

Ventricular action potential duration (APD) is an important component of many physiological functions including arrhythmogenesis. APD oscillations have recently been reported in humans at the respiratory frequency. This study investigates the contribution of the autonomic nervous system to these oscillations. In 10 patients undergoing treatment for supraventricular arrhythmias, activation recovery intervals (ARI; a conventional surrogate for APD) were measured from multiple left and right ventricular (RV) endocardial sites, together with femoral artery pressure. Respiration was voluntarily regulated and heart rate clamped by RV pacing. Sympathetic and parasympathetic blockade was achieved using intravenous metoprolol and atropine, respectively. Metroprolol reduced the rate of pressure development (maximal change in pressure over time): 1,271 (± 646) vs. 930 (± 433) mmHg/s; P < 0.01. Systolic blood pressure (SBP) showed a trend to decrease after metoprolol, 133 (± 21) vs. 128 (± 25) mmHg; P = 0.06, and atropine infusion, 122 (± 26) mmHg; P < 0.05. ARI and SBP exhibited significant cyclical variations (P < 0.05) with respiration in all subjects with peak-to-peak amplitudes ranging between 0.7 and 17.0 mmHg and 1 and 16 ms, respectively. Infusion of metoprolol reduced the mean peak-to-peak amplitude [ARI, 6.2 (± 1.4) vs. 4.4 (± 1.0) ms, P = 0.008; SBP, 8.4 (± 1.6) vs. 6.2 (± 2.0) mmHg, P = 0.002]. The addition of atropine had no significant effect. ARI, SBP, and respiration showed significant coupling (P < 0.05) at the breathing frequency in all subjects. Directed coherence from respiration to ARI was high and reduced after metoprolol infusion [0.70 (± 0.17) vs. 0.50 (± 0.23); P < 0.05]. These results suggest a role of respiration in modulating the electrophysiology of ventricular myocardium in humans, which is partly, but not totally, mediated by β-adrenergic mechanisms

Not fitting in and getting out : psychological type and congregational satisfaction among Anglican churchgoers in England

Listening to the motivations reported by individuals for ceasing church attendance and becoming church leavers, Francis and Richter identified high on the list the sense of "not fitting in". Drawing on psychological type theory, several recent studies have documented the way in which some psychological types are over-represented in church congregations and other psychological types are under-represented. Bringing these two observations together, the present study tested the hypothesis that church congregations have created type-alike communities within which individuals displaying the opposite type preferences are more likely to feel marginalised and to display lower levels of satisfaction with the congregations they attend. Data were provided by 1867 churchgoers who completed a measure of psychological type, together with measures of frequency of attendance and congregational satisfaction. These data confirmed that congregations were weighted towards preferences for introversion, sensing, feeling and judging, and that individuals displaying the opposite preferences (especially intuition, thinking and perceiving) recorded lower levels of congregational satisfaction. The implications of these findings are discussed for promoting congregational retention by enhancing awareness of psychological type preferences among those who attend

Loss of BAP1 Expression Is Very Rare in Pancreatic Ductal Adenocarcinoma

BACKGROUND: Pancreatic cancer is both common and highly lethal and therefore new biomarkers or potential targets for treatment are needed. Loss of BRCA associated protein-1 (BAP1) expression has been found in up to a quarter of intrahepatic cholangiocarcinomas. Given the close anatomical relationship between intrahepatic cholangiocarcinoma and pancreatic ductal adenocarcinoma, we therefore sought to investigate the frequency of loss of BAP1 expression in pancreatic ductal adenocarcinoma. METHODS: The records of the department of Anatomical Pathology Royal North Shore Hospital, Sydney, Australia, were searched for cases of pancreatic ductal adenocarcinoma diagnosed between 1992 and 2014 with material available in archived formalin fixed paraffin embedded tissue blocks. Immunohistochemistry for BAP1 was performed on tissue microarray sections and if staining was equivocal or negative it was confirmed on whole sections. Negative staining for BAP1 was defined as loss of expression in all neoplastic nuclei, with preserved expression in non-neoplastic cells which acted as an internal positive control. RESULTS: Loss of BAP1 expression was found in only 1 of 306 (0.33%) pancreatic ductal adenocarcinomas. This case was confirmed to demonstrate diffuse loss of expression throughout all neoplastic cells in multiple blocks, consistent with BAP1 loss being an early clonal event. All other cases demonstrated positive expression of BAP1. CONCLUSION: We conclude that, in contrast to intrahepatic cholangiocarcinoma, loss of expression of BAP1 occurs very rarely in pancreatic ductal adenocarcinoma. Therefore BAP1 inactivation is unlikely to be a frequent driver abnormality in pancreatic adenocarcinoma

A computational proof of locality in entanglement

In this paper the design and proof of concept (POC) coding of a local hidden variables computer model is presented. The program violates the Clauser, Horne, Shimony and Holt inequality $|$CHSH$|$ $\leq 2$. In our numerical experiment, we find with our local computer program, CHSH $\approx 1 + \sqrt{2}$