Mitochondrial implications in human pregnancies with intrauterine growth restriction and associated cardiac remodelling

Intrauterine growth restriction (IUGR) is an obstetric complication characterised by placental insufficiency and secondary cardiovascular remodelling that can lead to cardiomyopathy in adulthood. Despite its aetiology and potential therapeutics are poorly understood, bioenergetic deficits have been demonstrated in adverse foetal and cardiac development. We aimed to evaluate the role of mitochondria in human pregnancies with IUGR. In a single‐site, cross‐sectional and observational study, we included placenta and maternal peripheral and neonatal cord blood mononuclear cells (PBMC and CBMC) from 14 IUGR and 22 control pregnancies. The following mitochondrial measurements were assessed: enzymatic activities of mitochondrial respiratory chain (MRC) complexes I, II, IV, I + III and II + III, oxygen consumption (cell and complex I‐stimulated respiration), mitochondrial content (citrate synthase [CS] activity and mitochondrial DNA copy number), total ATP levels and lipid peroxidation. Sirtuin3 expression was evaluated as a potential regulator of bioenergetic imbalance. Intrauterine growth restriction placental tissue showed a significant decrease of MRC CI enzymatic activity (P < 0.05) and CI‐stimulated oxygen consumption (P < 0.05) accompanied by a significant increase of Sirtuin3/β‐actin protein levels (P < 0.05). Maternal PBMC and neonatal CBMC from IUGR patients presented a not significant decrease in oxygen consumption (cell and CI‐stimulated respiration) and MRC enzymatic activities (CII and CIV). Moreover, CS activity was significantly reduced in IUGR new‐borns (P < 0.05). Total ATP levels and lipid peroxidation were preserved in all the studied tissues. Altered mitochondrial function of IUGR is especially present at placental and neonatal level, conveying potential targets to modulate obstetric outcome through dietary interventions aimed to regulate Sirtuin3 function.     

Robustness and stability of the gene regulatory network involved in DV boundary formation in the Drosophila wing

Gene regulatory networks have been conserved during evolution. The Drosophila wing and the vertebrate hindbrain share the gene network involved in the establishment of the boundary between dorsal and ventral compartments in the wing and adjacent rhombomeres in the hindbrain. A positive feedback-loop between boundary and non-boundary cells and mediated by the activities of Notch and Wingless/Wnt-1 leads to the establishment of a Notch dependent organizer at the boundary. By means of a Systems Biology approach that combines mathematical modeling and both in silico and in vivo experiments in the Drosophila wing primordium, we modeled and tested this regulatory network and present evidence that a novel property, namely refractoriness to the Wingless signaling molecule, is required in boundary cells for the formation of a stable dorsal-ventral boundary. This new property has been validated in vivo, promotes mutually exclusive domains of Notch and Wingless activities and confers stability to the dorsal-ventral boundary. A robustness analysis of the regulatory network complements our results and ensures its biological plausibility.     

Tumor ablation with irreversible electroporation

We report the first successful use of irreversible electroporation for the minimally invasive treatment of aggressive cutaneous tumors implanted in mice. Irreversible electroporation is a newly developed non-thermal tissue ablation technique in which certain short duration electrical fields are used to permanently permeabilize the cell membrane, presumably through the formation of nanoscale defects in the cell membrane. Mathematical models of the electrical and thermal fields that develop during the application of the pulses were used to design an efficient treatment protocol with minimal heating of the tissue. Tumor regression was confirmed by histological studies which also revealed that it occurred as a direct result of irreversible cell membrane permeabilization. Parametric studies show that the successful outcome of the procedure is related to the applied electric field strength, the total pulse duration as well as the temporal mode of delivery of the pulses. Our best results were obtained using plate electrodes to deliver across the tumor 80 pulses of 100 micros at 0.3 Hz with an electrical field magnitude of 2500 V/cm. These conditions induced complete regression in 12 out of 13 treated tumors, (92%), in the absence of tissue heating. Irreversible electroporation is thus a new effective modality for non-thermal tumor ablation.     

犬齿窝与人类中面部骨骼的演化

犬齿窝是包括现代人类在内的许多人族成员面部骨骼的重要性状,但在分类学上的意义仍存在争议。有学者认为该性状是一个发生于基础面形的近祖性状,除了一些例外,在灭绝和现生的大猿及人属中都存在。另有学者认为,犬齿窝是仅存在于智人及其直系祖先的衍生性状,在发育上与颧齿槽突嵴有关。这种关系并非总是成立,在智人中存在着明显的差异：弧型颧齿槽突嵴和直斜型颧齿槽突嵴与犬齿窝有时共存,有时不共存。我们由此推测,犬齿窝的发生和形态与上颌窦的前部发育有关,颧齿槽突嵴的形态与鼻窦的侧面发育有关。在人类演化的过程中,犬齿窝经历了不同的变形,比如上颌沟(如南方古猿非洲种、傍人粗壮种)、上颌小窝(如傍人粗壮种)、上颌沟(如匠人)或犬齿窝缺如(如傍人埃塞俄比亚种、傍人鲍氏种、肯尼亚扁脸人、人属鲁道夫种)。犬齿窝消失的原因各类群并不相同,如中新世和早更新世人属以及中更新世人属(如人属海德堡种/人属罗得西亚种、人属尼安德特种)。人属罗得西亚种具有弱化的犬齿窝,不具备演化为智人的可能,因此被排除在智人的演化支之外。     

A balance index for phylogenetic trees based on rooted quartets

Journal of Mathematical Biology - We define a new balance index for rooted phylogenetic trees based on the symmetry of the evolutive history of every set of 4 leaves. This index makes sense for...     

Comparison of the most demanding scenarios during different in-season training sessions and official matches in professional basketball players

The purpose of this study was to compare physical demands during the most demanding scenarios (MDS) of different training sessions and official matches in professional basketball players across playing positions. Thirteen professional basketball players were monitored over a 9-week competitive season using a local positioning system. Peak physical demands included total distance, distance covered at > 18 km·h^-1, distance and number of accelerations (≥ 2 m∙s^-2) and decelerations (≤ -2 m∙s^-2) over a 60-second epoch. Analysis of variance for repeated measures, Bonferroni post-hoc tests and standardised Cohen’s effect size (ES) were calculated. Overall, almost all physical demands during the MDS of training were lower (-6.2% to -35.4%) compared to official matches. The only variable that surpassed competition demands was distance covered at > 18 km·h^-1, which presented moderate (ES = 0.61, p = 0.01) and small (ES = 0.48, p > 0.05) increases during training sessions four and three days before a competition, respectively. Conversely, the two previous practices before match day presented trivial to very large decreases (ES = 0.09–2.66) in all physical demands. Furthermore, centres achieved the lowest peak value in total distance covered during matches, forwards completed the greatest peak distance at > 18 km·h^-1, and guards performed the greatest distance and number of high-intensity accelerations and decelerations. In conclusion, physical demands during the MDS of different training sessions across the microcycle failed to match or surpass peak values during official matches, which should be considered when prescribing a training process intended to optimise the MDS of match play.