Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function

Left ventricular mass (LVM) is a highly heritable trait and an independent risk factor for all-cause mortality. So far, genome-wide association studies have not identified the genetic factors that underlie LVM variation, and the regulatory mechanisms for blood-pressure-independent cardiac hypertrophy remain poorly understood. Unbiased systems genetics approaches in the rat now provide a powerful complementary tool to genome-wide association studies, and we applied integrative genomics to dissect a highly replicated, blood-pressure-independent LVM locus on rat chromosome 3p. Here we identified endonuclease G (Endog), which previously was implicated in apoptosis but not hypertrophy, as the gene at the locus, and we found a loss-of-function mutation in Endog that is associated with increased LVM and impaired cardiac function. Inhibition of Endog in cultured cardiomyocytes resulted in an increase in cell size and hypertrophic biomarkers in the absence of pro-hypertrophic stimulation. Genome-wide network analysis unexpectedly implicated ENDOG in fundamental mitochondrial processes that are unrelated to apoptosis. We showed direct regulation of ENDOG by ERR-α and PGC1α (which are master regulators of mitochondrial and cardiac function), interaction of ENDOG with the mitochondrial genome and ENDOG-mediated regulation of mitochondrial mass. At baseline, the Endog-deleted mouse heart had depleted mitochondria, mitochondrial dysfunction and elevated levels of reactive oxygen species, which were associated with enlarged and steatotic cardiomyocytes. Our study has further established the link between mitochondrial dysfunction, reactive oxygen species and heart disease and has uncovered a role for Endog in maladaptive cardiac hypertrophy.     

Messinian salinity crisis regulated by competing tectonics and erosion at the Gibraltar arc

The Messinian salinity crisis (5.96 to 5.33 million years ago) was caused by reduced water inflow from the Atlantic Ocean to the Mediterranean Sea resulting in widespread salt precipitation and a decrease in Mediterranean sea level of about 1.5 kilometres due to evaporation. The reduced connectivity between the Atlantic and the Mediterranean at the time of the salinity crisis is thought to have resulted from tectonic uplift of the Gibraltar arc seaway and global sea-level changes, both of which control the inflow of water required to compensate for the hydrological deficit of the Mediterranean. However, the different timescales on which tectonic uplift and changes in sea level occur are difficult to reconcile with the long duration of the shallow connection between the Mediterranean and the Atlantic needed to explain the large amount of salt precipitated. Here we use numerical modelling to show that seaway erosion caused by the Atlantic inflow could sustain such a shallow connection between the Atlantic and the Mediterranean by counteracting tectonic uplift. The erosion and uplift rates required are consistent with previous mountain erosion studies, with the present altitude of marine sediments in the Gibraltar arc and with geodynamic models suggesting a lithospheric slab tear underneath the region. The moderate Mediterranean sea-level drawdown during the early stages of the Messinian salinity crisis can be explained by an uplift of a few millimetres per year counteracted by similar rates of erosion due to Atlantic inflow. Our findings suggest that the competition between uplift and erosion can result in harmonic coupling between erosion and the Mediterranean sea level, providing an alternative mechanism for the cyclicity observed in early salt precipitation deposits and calling into question previous ideas regarding the timing of the events that occurred during the Messinian salinity crisis.     

Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells

Human induced pluripotent stem cells (iPSCs) represent a unique opportunity for regenerative medicine because they offer the prospect of generating unlimited quantities of cells for autologous transplantation, with potential application in treatments for a broad range of disorders. However, the use of human iPSCs in the context of genetically inherited human disease will require the correction of disease-causing mutations in a manner that is fully compatible with clinical applications. The methods currently available, such as homologous recombination, lack the necessary efficiency and also leave residual sequences in the targeted genome. Therefore, the development of new approaches to edit the mammalian genome is a prerequisite to delivering the clinical promise of human iPSCs. Here we show that a combination of zinc finger nucleases (ZFNs) and piggyBac technology in human iPSCs can achieve biallelic correction of a point mutation (Glu342Lys) in the α(1)-antitrypsin (A1AT, also known as SERPINA1) gene that is responsible for α(1)-antitrypsin deficiency. Genetic correction of human iPSCs restored the structure and function of A1AT in subsequently derived liver cells in vitro and in vivo. This approach is significantly more efficient than any other gene-targeting technology that is currently available and crucially prevents contamination of the host genome with residual non-human sequences. Our results provide the first proof of principle, to our knowledge, for the potential of combining human iPSCs with genetic correction to generate clinically relevant cells for autologous cell-based therapies.     

葡萄牙松材线虫与其媒介昆虫之间的互作Pedro Miguel Naves, Luís Bonifácio, Edmundo Sousa

对松材线虫与其在葡萄牙和欧洲的媒介昆虫樟子松墨天牛（Monochamus galloprovincialis）进行了首次研究。在病死木中发现,松材线虫在天牛刚羽化时聚集在蛹室中,线虫主要集中在天牛的后胸部。天牛羽化后6周内,松材线虫主要在天牛成虫补充营养时进入新寄主树,其次在天牛产卵时也会进入寄主树。总的看来,松材线虫在欧洲与其携带天牛之间互作与其在亚洲与松墨天牛及在北美与卡来罗纳墨天牛之间的关系十分相似。经研究,影响线虫与天牛携带关系的因子有内源和外源两类因子,如化学气味和各种信号。但是,其他多数因子尚未了解。研究影响线虫与天牛携带关系的因子将有助于了解两种生物密切关系的内在机制,并有助于研发出新的防控方法。     

Effect of storage conditions on long-term stability of Ag nanoparticles formed via green synthesis

Spherical Ag nanoparticles (AgNPs) with a diameter of 20 nm or smaller were biologically synthesized using algae Parachlorella kessleri. The effect of storage conditions on the long-term stability of AgNPs was investigated. UV/Vis spectrophotometry, transmission electron microscopy, and dynamic light scattering measurements revealed that the long-term stability of AgNPs was influenced by light and temperature conditions. The most significant loss of stability was observed for the AgNPs stored in daylight at room temperature. The AgNPs stored under these conditions began to lose their stability after approximately 30 d; after 100 d, a substantial amount of agglomerated particles settled to the bottom of the Erlenmeyer flask. The AgNPs stored in the dark at room temperature exhibited better long-term stability. Weak particle agglomeration began at approximately the 100th day. The AgNPs stored in the dark at about 5℃ exhibited the best long-term stability; the AgNPs stored under such conditions remained spherical, with a narrow size distribution, and stable (no agglomeration) even after 6 months. Zeta-potential measurements confirmed better dispersity and stability of AgNPs stored under these conditions.     

A Systemic Framework to Develop Sustainable Engineering Solutions in Rural Communities in Colombia

In several rural areas in Colombia there is a serious lack of water quality supply. Thereby the problematic situation is understood as complex one that involves stakeholders with pluralistic interests, multiple variables and requires the development of sustainable and suitable solutions. In order to address this issue, this paper proposes an integration of engineering design framework (CDIO) with a systemic approach. Particularly the approach emphasizes on systemic elements such as autonomy, systems within systems, cooperation between stakeholders and cause effect relations; it also proposes a previous observing phase for engineering design framework. Thus the proposed systemic framework aims to generate projects that improve living conditions in rural communities and promote the production of knowledge between the stakeholders to ensure sustainability in the long term. To illustrate the proposal, this work contains a case study that discusses a project carried out by a research team—Ingenieros Sin Fronteras Colombia—in a rural district near to Colombia’s capital. The experience, which involved and benefited 16 families in the community, provided strong evidence to support the proposed framework. The paper concludes with a discussion about the replication of this proposal in other contexts.     

Non-monogamous mating system and evidence of lekking behaviour in the Helmeted Manakin (Aves: Pipridae)

ABSTRACT

Manakins (Pipridae) are a group of Neotropical birds well known for their spectacular lekking displays and non-monogamous mating system. Nevertheless, the two species of Antilophia have been traditionally considered monogamous and, therefore, an exception to this rule. In this paper, we studied the home range and the mating system of a colour-ringed population of the Helmeted Manakin Antilophia galeata in southeastern Brazil. We propose that it is a non-monogamous species that ranges widely during the breeding season, presenting a lekking behaviour in the form of unspectacular but aggressive chasing courtship displays.     

New record and southern range extension for the Mearn's grasshopper mouse ( Onychomys arenicola Mearns, 1896) in Veracruz, Mexico

Mearn’s grasshopper mouse ( Onychomys arenicola ) in Mexico is found primarily in the central and northern states. This is the first report of the genus Onychomys in the state of Veracruz, based on 7 captured specimens (3 collected). This finding extends the species’ known distribution by approximately 470 km east-southeast. In addition, this record increases the alpha diversity of terrestrial mammals for the state of Veracruz to 192 species.