The ancient function of RB-E2F Pathway: insights from its evolutionary history

<p>Abstract</p> <p>Background</p> <p>The RB-E2F pathway is conserved in most eukaryotic lineages, including animals and plants. E2F and RB family proteins perform crucial functions in cycle controlling, differentiation, development and apoptosis. However, there are two kinds of E2Fs (repressive E2Fs and active E2Fs) and three RB family members in human. Till now, the detail evolutionary history of these protein families and how RB-E2F pathway evolved in different organisms remain poorly explored.</p> <p>Results</p> <p>We performed a comprehensive evolutionary analysis of E2F, RB and DP (dimerization partners of E2Fs) protein family in representative eukaryotic organisms. Several interesting facts were revealed. First, orthologues of RB, E2F, and DP family are present in several representative unicellular organisms and all multicellular organisms we checked. Second, ancestral E2F, RB genes duplicated before placozoans and bilaterians diverged, thus E2F family was divided into E2F4/5 subgroup (including repressive E2Fs: E2F4 and E2F5) and E2F1/2/3 subgroup (including active E2Fs: E2F1, E2F2 and E2F3), RB family was divided into RB1 subgroup (including RB1) and RBL subgroup (including RBL1 and RBL2). Third, E2F4 and E2F5 share more sequence similarity with the predicted E2F ancestral sequence than E2F1, E2F2 and E2F3; E2F4 and E2F5 also possess lower evolutionary rates and higher purification selection pressures than E2F1, E2F2 and E2F3. Fourth, for RB family, the RBL subgroup proteins possess lower evolutionary rates and higher purification selection pressures compared with RB subgroup proteins in vertebrates,</p> <p>Conclusions</p> <p>Protein evolutionary rates and purification selection pressures are usually linked with protein functions. We speculated that function conducted by E2F4/5 subgroup and RBL subgroup proteins might mainly represent the ancient function of RB-E2F pathway, and the E2F1/2/3 subgroup proteins and RB1 protein might contribute more to functional diversification in RB-E2F pathway. Our results will enhance the current understanding of RB-E2F pathway and will also be useful to further functional studies in human and other model organisms.</p> <p>Reviewers</p> <p>This article was reviewed by Dr. Pierre Pontarotti, Dr. Arcady Mushegian and Dr. Zhenguo Lin (nominated by Dr. Neil Smalheiser).</p

Road proximity and traffic flow perceived as potential predation risks: evidence from the Tibetan antelope

Abstract Context. The risk-disturbance hypothesis predicts that animals exhibit risk-avoidance behaviours when exposed to human disturbance because they perceive the disturbance as a predatory threat. Aims. This study aimed to examine whether Tibetan antelopes (Pantholops hodgsoni) exhibit risk-avoidance behaviour with proximity to a major highway and with increasing traffic flow consistent with the risk-disturbance hypothesis. Methods. Focal-animal sampling was used to observe the behaviour of Tibetan antelopes. The behaviours were categorised as foraging, vigilance, resting, moving, or other. The time, frequency, and duration of foraging and vigilance were calculated. Key results. As distance from the road increased, time spent foraging and foraging duration increased while foraging frequency, time spent being vigilant and vigilance frequency decreased, indicating that there is a risk perception associated with roads. Tibetan antelopes presented more risk-avoidance behaviours during high-traffic periods compared with lowtraffic periods. Conclusions. Tibetan antelopes exhibited risk-avoidance behaviour towards roads that varied with proximity and traffic levels, which is consistent with the risk-disturbance hypothesis. Implications. The consequences of risk-avoidance behaviour should be reflected in wildlife management by considering human disturbance and road design

Case Report: Giant left atrial cystic tumor: myxoma or intracardiac blood cyst?

BackgroundPrimary cardiac tumors are uncommon, with the majority being benign myxomas. Cystic myxoma, a particularly rare type of benign cardiac tumor, demands cautious differential diagnosis from other cardiac tumors.Case summaryA 43-year-old male patient presenting with intermittent dyspnea was referred to our department for surgical evaluation. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) unveiled an intra-left atrial cyst, which was subsequently found to be blood-filled during a video-assisted microinvasive heart surgery. Pathological examination depicted a cyst wall filled with small stellate and fat spindle cells, along with a mucoid matrix, indicating a diagnosis of cystic myxoma.ConclusionsWe herein presented a rare case of an adult patient with cystic myxoma, initially misdiagnosed as an intracardiac blood cyst (CBC) prior to surgery, and ultimately verified via pathological findings

Lack of Trehalose Accelerates H2O2-Induced Candida albicans Apoptosis through Regulating Ca2+ Signaling Pathway and Caspase Activity

Trehalose is a non-reducing disaccharide and can be accumulated in response to heat or oxidative stresses in Candida albicans. Here we showed that a C. albicans tps1Δ mutant, which is deficient in trehalose synthesis, exhibited increased apoptosis rate upon H2O2 treatment together with an increase of intracellular Ca2+ level and caspase activity. When the intracellular Ca2+ level was stimulated by adding CaCl2 or A23187, both the apoptosis rate and caspase activity were increased. In contrast, the presence of two calcium chelators, EGTA and BAPTA, could attenuate these effects. Moreover, we investigated the role of Ca2+ pathway in C. albicans apoptosis and found that both calcineurin and the calcineurin-dependent transcription factor, Crz1p, mutants showed decreased apoptosis and caspase activity upon H2O2 treatment compared to the wild-type cells. Expression of CaMCA1, the only gene found encoding a C. albicans metacaspase, in calcineurin-deleted or Crz1p-deleted cells restored the cell sensitivity to H2O2. Our results suggest that Ca2+ and its downstream calcineurin/Crz1p/CaMCA1 pathway are involved in H2O2 -induced C. albicans apoptosis. Inhibition of this pathway might be the mechanism for the protective role of trehalose in C. albicans

Associations between long-term blood pressure trajectory and all-cause and CVD mortality among old people in China

BackgroundOptimal blood pressure (BP) management strategy among the elderly remains controversial, with insufficient consideration of long-term BP trajectory. This study aimed to identify BP trajectory patterns as well as terminal BP trajectory among the Chinese elderly and to explore the relationships between BP trajectories and all-cause mortality and cardiovascular disease (CVD) mortality.MethodsWe included 11,181 participants older than 60 at baseline (mean age, 80.98 ± 10.71) with 42,871 routine BP measurements from the Chinese Longitudinal Healthy Longevity Survey. Latent class trajectory analysis and Cox proportional hazard model were conducted to identify trajectory patterns and their associations with mortality. Furthermore, we also applied mixed-effects model to identify terminal BP trajectories among the elderly.ResultsCompared with stable at normal high level trajectory, excess systolic BP (SBP) trajectory with decreasing trend was associated with a 34% (HR = 1.34, 95% CI: 1.23–1.45) higher risk of all-cause mortality. Considering the competing risk of non-CVD death, excess BP trajectory with decreasing trend had a more pronounced effect on CVD mortality, in which HR (95% CI) was 1.67 (1.17, 2.37). Similar results were also found in diastolic BP (DBP), pulse pressure (PP), and mean arterial pressure (MAP) trajectories. We further conducted a mixed-effects model and observed that SBP and PP trajectories first increased and began to decline slightly six years before death. In contrast, DBP and MAP showed continuous decline 15 years before death.ConclusionLong-term BP trajectory was associated with all-cause mortality, especially CVD mortality. Keeping a stable BP over time may be an important way for CVD prevention among the elderly

Effect of minor Sc and Zr addition on grain refi nement of as-cast Al-Zn-Mg-Cu alloys

The optical microscopy and scanning electron microscopy as well as energy dispersive spectroscopy were employed to investigate the infl uence of joint addition of Sc and Zr on grain refi nement of Al-Zn-Mg-Cu alloys.Results show that the addition of 0.20% Sc has a little effect on grain refi nement because Sc is mainly dissolved into the matrix and hardly any primary Al3Sc particles are precipitated. The alloy with addition of 0.30% Sc and 0.16% Zr has more equiaxed grains than that of others, giving cast grain sizes as fi ne as 13 μm. This is because the Sc substitutes for Al atom in the Al-Zr crystal cell and forms Al-Sc-Zr unit cell, which grows and becomes Al3(Scx,Zr1-x) particle, acting as a nucleus for the formation of α-Al. The addition of 0.04% Ti and 0.008% B makes the grain size drop from 250 μm to 50 μm. Its refi nement effect is less than the 13 μm achieved by the alloy including 0.30% Sc and 0.16% Zr

Experimental Research on Shear Ductility of Regional Confined Concrete Beam

In efforts to study the shear ductility of regional confined concrete beam, 5 reinforced concrete beams were tested to examine its shear performance. These beams has the same shear span ratio, concrete strength, different ratios of tension reinforcement and shapes of stirrup. The purpose of the test is studying the effects of stirrup shape and tension reinforcement ratio on failure mode and shear ductility. The test shows that the regional confined part can be used as an independent part and the rest of the beam is good to work together so that the ductility of the beam is more one time higher than that of the normal confined concrete beam. The related laws of the effect of tension reinforcement ratio and stirrup shapes on beam's shear ductility were founde

Experimental Research on Shear Ductility of Regional Confined Concrete Beam

In efforts to study the shear ductility of regional confined concrete beam, 5 reinforced concrete beams were tested to examine its shear performance. These beams has the same shear span ratio, concrete strength, different ratios of tension reinforcement and shapes of stirrup. The purpose of the test is studying the effects of stirrup shape and tension reinforcement ratio on failure mode and shear ductility. The test shows that the regional confined part can be used as an independent part and the rest of the beam is good to work together so that the ductility of the beam is more one time higher than that of the normal confined concrete beam. The related laws of the effect of tension reinforcement ratio and stirrup shapes on beam's shear ductility were founde