Obesity is a common soil for premature cardiac aging and heart diseases - Role of autophagy

The advance in medical technology and healthcare has dramatically improved the average human lifespan. One of the consequences for longevity is the high prevalence of aging-related chronic disorders such as cardiovascular diseases, cancer and metabolic abnormalities. As the composition of aging population is raising in western countries, heart failure remains the number one cause of death with a more severe impact in the elderly. Obesity and aging are the most critical risk factors for increased susceptibility to heart failure in developing and developed countries. Numerous population-based and experimental data have depicted a close relationship between the age-related diseases and obesity. There is an overall agreement that obesity is causally linked to the development of cardiovascular disorders and severe premature cardiac aging. Accumulating evidence indicates that autophagy plays an important role in obesity, cardiac aging and diseases. In this review, we will focus on the role of autophagy in obesity-related cardiac aging and diseases, and how it regulates age-dependent changes in the heart.     

Current developments and future directions of bio-inspired computation and implications for ecoinformatics

Evolutionary and neural computation has been used widely in solving various problems in biological ecosystems. This paper reviews some of the recent work in evolutionary computation and neural network ensembles that could be explored further in the context of ecoinformatics. Although these bio-inspired techniques were not developed specifically for ecoinformatics, their successes in solving complex problems in other fields demonstrate how these techniques could be adapted and used for tackling difficult problems in ecoinformatics. Firstly, we will review our work in modelling and model calibration, which is an important topic in ecoinformatics. Secondly one example will be given to illustrate how coevolutionary algorithms could be used in problem-solving. Thirdly, we will describe our work on neural network ensembles, which can be used for various classification and prediction problems in ecoinformatics. Finally, we will discuss ecosystem-inspired computational models and algorithms that could be explored as directions of future research.     

Recent advances in heart regeneration

Although cardiac stem cells (CSCs) and tissue engineering are very promising for cardiac regenerative medicine, studies with model organisms for heart regeneration will provide alternative therapeutic targets and opportunities. Here, we present a review on heart regeneration, with a particular focus on the most recent work in mouse and zebrafish. We attempt to summarize the recent progresses and bottlenecks of CSCs and tissue engineering for heart regeneration; and emphasize what we have learned from mouse and zebrafish regenerative models on discovering crucial genetic and epigenetic factors for stimulating heart regeneration; and speculate the potential application of these regenerative factors for heart failure. A brief perspective highlights several important and promising research directions in this exciting field. Birth Defects Research (Part C) 99:160–169, 2013. © 2013 Wiley Periodicals, Inc.     

As time flies by: Investigating cardiac aging in the short-lived Drosophila model

Aging is associated with a decline in heart function across the tissue, cellular, and molecular levels. The risk of cardiovascular disease grows significantly over time, and as developed countries continue to see an increase in lifespan, the cost of cardiovascular healthcare for the elderly will undoubtedly rise. The molecular basis for cardiac function deterioration with age is multifaceted and not entirely clear, and there is a limit to what investigations can be performed on human subjects or mammalian models. Drosophila melanogaster has emerged as a useful model organism for studying aging in a short timeframe, benefitting from a suite of molecular and genetic tools and displaying highly conserved traits of cardiac senescence. Here, we discuss recent advances in our understanding of cardiac aging and how the fruit fly has aided in these developments.     

Mutations in voltage-gated L-type calcium channel: implications in cardiac arrhythmia

The voltage-gated L-type calcium channel (LTCC) is essential for multiple cellular processes. In the heart, calcium influx through LTCC plays an important role in cardiac electrical excitation. Mutations in LTCC genes, including CACNA1C, CACNA1D, CACNB2 and CACNA2D, will induce the dysfunctions of calcium channels, which result in the abnormal excitations of cardiomyocytes, and finally lead to cardiac arrhythmias. Nevertheless, the newly found mutations in LTCC and their functions are continuously being elucidated. This review summarizes recent findings on the mutations of LTCC, which are associated with long QT syndromes, Timothy syndromes, Brugada syndromes, short QT syndromes, and some other cardiac arrhythmias. Indeed, we describe the gain/loss-of-functions of these mutations in LTCC, which can give an explanation for the phenotypes of cardiac arrhythmias. Moreover, we present several challenges in the field at present, and propose some diagnostic or therapeutic approaches to these mutation-associated cardiac diseases in the future.     

家兔心跳骤停复苏模型的研究进展

心跳骤停是临床医学中最为危急的事件之一,其发生发展过程涉及了一系列的病理生理学改变。近几年来,有关于心跳骤停复苏的研究有很多,也取得了一定的进展,但关于其各种不同类型心跳骤停的病理生理学改变的理解仍不是十分的全面,其有效地治疗药物和治疗手段也仍需要进一步的研究。因此,成功地制备与人类心跳骤停相似的动物模型就显得非常必要来,这不仅是深入研究心跳骤停复苏病理生理学改变的重要基础和研究途径,也是研制其治疗药物及方法的有效手段。本文重点讨论家兔各种类型心跳骤停复苏模型不同的研究方法。     

New horizons for building pyrenoid-based CO2-concentrating mechanisms in plants to improve yields

Many photosynthetic species have evolved CO₂-concentrating mechanisms (CCMs) to improve the efficiency of CO₂ assimilation by Rubisco and reduce the negative impacts of photorespiration. However, the majority of plants (i.e. C3 plants) lack an active CCM. Thus, engineering a functional heterologous CCM into important C3 crops, such as rice (Oryza sativa) and wheat (Triticum aestivum), has become a key strategic ambition to enhance yield potential. Here, we review recent advances in our understanding of the pyrenoid-based CCM in the model green alga Chlamydomonas reinhardtii and engineering progress in C3 plants. We also discuss recent modeling work that has provided insights into the potential advantages of Rubisco condensation within the pyrenoid and the energetic costs of the Chlamydomonas CCM, which, together, will help to better guide future engineering approaches. Key findings include the potential benefits of Rubisco condensation for carboxylation efficiency and the need for a diffusional barrier around the pyrenoid matrix. We discuss a minimal set of components for the CCM to function and that active bicarbonate import into the chloroplast stroma may not be necessary for a functional pyrenoid-based CCM in planta. Thus, the roadmap for building a pyrenoid-based CCM into plant chloroplasts to enhance the efficiency of photosynthesis now appears clearer with new challenges and opportunities.

Research on pyrenoid formation has led to key advances toward engineering an algal CO₂-concentrating mechanism into C3 land plants, and a recent model predicts an optimized pathway for future work.     

Drosophila, an emerging model for cardiac disease

A variety of studies that are currently underway may validate the fruit fly as an in vivo model for analyzing genes involved in cardiac function. Many mutations in conserved genetic pathways have been found, including those controlling development and physiology. Because homologous genes control early developmental events as well as functional components of the Drosophila and vertebrate hearts, the fly is the simplest existing model system that can be used to assay genes involved in human congenital heart disease (CHD). The wide variety of genetic tools available to Drosophila researchers offers many technical advantages for rapidly screening through large numbers of candidate genes. Thus, an important future and long-term direction is likely to be the use of Drosophila as a vehicle for analyzing polygenic traits as an aid in human genetics. One can anticipate a time in the not too distant future when mutant lines exist for every gene in vertebrate systems, such as mice and zebrafish. However, one of the enduring problems that will not easily be addressed by such resources will be the tracking of complex traits defined by polygenic variants. For this level of genetic analysis, simple genetic model systems including yeast, Caenorhabditis elegans, and Drosophila melanogaster will undoubtedly play a crucial ongoing role. Of them, Drosophila will be critical for examining gene networks involved in organogenesis and is clearly the system of choice for studying cardiac development, function and aging, since among the simple genetic models it is the only one with a fluid pumping heart.     

Zebrafish genetic models for arrhythmia

Over the last decade the zebrafish has emerged as a major genetic model organism. While stimulated originally by the utility of its transparent embryos for the study of vertebrate organogenesis, the success of the zebrafish was consolidated through multiple genetic screens, sequencing of the fish genome by the Sanger Center, and the advent of extensive genomic resources. In the last few years the potential of the zebrafish for in vivo cell biology, physiology, disease modeling and drug discovery has begun to be realized. This review will highlight work on cardiac electrophysiology, emphasizing the arenas in which the zebrafish complements other in vivo and in vitro models; developmental physiology, large-scale screens, high-throughput disease modeling and drug discovery. Much of this work is at an early stage, and so the focus will be on the general principles, the specific advantages of the zebrafish and on future potential.     

Digitalis: new actions for an old drug

The mechanisms by which digitalis causes its therapeutic and toxic actions have been studied for nearly a half century, revealing a great deal about cardiac cell regulation of intracellular ions via the Na-K-ATPase (NKA) and how it is altered by cardiac glycosides. However, recent observations suggest that digitalis may have additional effects on cardiac cell function in both the short and long term that include intracellular effects, interactions with specific NKA isoforms in different cellular locations, effects on intracellular (including nuclear) signaling, and long-term regulation of intracellular ionic balances through circulating ouabain-like compounds. The purpose of this review is to examine the current status of a number of the newest and most interesting developments in the study of digitalis with a particular focus on cardiac function, although we will also discuss some of the new advances in other relevant cardiovascular effects. This new information has important implications for both our understanding of ionic regulation in normal and diseased hearts as well as for potential avenues for the development of future therapeutic interventions for the treatment of heart failure.     

Rice MAPKs

Mitogen-activated protein kinase (MAPK) cascades are evolutionary conserved from unicellular to complex eukaryotic organisms, and constitute one of the major signalling pathways involved in regulating a wide range of cellular activities from growth and development to cell death. MAPKs of rice (Oryza sativa L.), the most important of all food crops and an established monocot plant research model, have seen considerable progress mainly on their identification and characterization during the past one year alone. These studies have provided new information on the response and regulation of rice MAPKs, in particular on their possible role/function in the rice self-defense pathways. It is believed that further work on MAPK cascades in rice will widen our understanding of the MAPK signalling pathways, and may lead to the establishment of a biological model on this critical early signalling event in monocots. In this review, we bring together all the recent developments in rice MAPKs and discuss their significance and future direction in light of the present data and the progress made in dicot model plants.     

Increased occurrence of out-of-hospital cardiac arrest on Mondays in a community-based study

Acute myocardial infarction and sudden cardiac death are more common on Mondays than other days of the week. The stress of returning to work at the beginning of the week has been postulated as a possible trigger factor. This project examined the weekly variation of out-of-hospital cardiac arrests of nontraumatic origin for the entire case series as well as for selected subgroups. A retrospective analysis of 1,498 incidences between January 1, 1995 and December 31, 1996 revealed a distinct Monday peak in occurrence irrespective of age, gender, presence of witnesses, primary survival, or primary ECG. This finding, however, was most pronounced in retired patients, subjects living alone, and persons found unconscious outside buildings or in public places. One important trigger of cardiac arrest is going to work after weekends; however, resumption of social and other activities on Mondays is another possible trigger. Other factors, such as endogenous biological rhythms, may contribute to an increased risk at this particular time even in elderly.     

以透明脑,观澄明心——斑马鱼神经功能研究进展

斑马鱼是一种相对新颖的模式脊椎动物,具有脊椎动物保守的神经系统构造和丰富的行为模式.近年来随着在体电生理、光学成像、遗传工程等方法的建立和完善,幼龄斑马鱼因其脑部透明、结构简单的特点,日益成为从突触、神经元、环路到行为等多层次,在全脑尺度上探究神经系统功能机制的理想动物模型.本文综述了近年来利用斑马鱼在感觉信息处理、运动控制、学习与神经可塑性等方向上所取得的重要研究进展,并对新技术的开发提出了展望.随着研究思路的深化和实验手段的推陈出新,斑马鱼模式动物必将成为探索脑工作原理之利器,为神经科学研究带来更多的突破.     

Zebrafish models in cardiac development and congenital heart birth defects

The zebrafish has become an ideal vertebrate animal system for investigating cardiac development due to its genetic tractability, external fertilization, early optical clarity and ability to survive without a functional cardiovascular system during development. In particular, recent advances in imaging techniques and the creation of zebrafish transgenics now permit the in vivo analysis of the dynamic cellular events that transpire during cardiac morphogenesis. As a result, the combination of these salient features provides detailed insight as to how specific genes may influence cardiac development at the cellular level. In this review, we will highlight how the zebrafish has been utilized to elucidate not only the underlying mechanisms of cardiac development and human congenital heart diseases (CHDs), but also potential pathways that may modulate cardiac regeneration. Thus, we have organized this review based on the major categories of CHDs-structural heart, functional heart, and vascular/great vessel defects, and will conclude with how the zebrafish may be further used to contribute to our understanding of specific human CHDs in the future.     

Research strategies in the pharmaceutical industry to cope with the problems of ageing

The present research strategies for ageing are focussed around three areas. The first area is the demographic study of the present-day populations and those in the future. The analysis of the evolution of the metropolitan French population from 1950 to 2050 indicates that the proportion of subjects aged greater than 60 years will pass from 16% to 35%. In addition, the level of dependence of these subjects will vary considerably from one to another. The second area is the integration of epidemiological data of the pathologies related to the aged subject. Numerous epidemiological studies of the aged show that the elderly population is in better health, better informed about the diseases that affect them and also financially more secure, which allows them to take better care of themselves. The epidemiological studies of certain dementias show, for example, that if we reduce the delay to when the disease appears by five years, then we reduce the prevalence by a factor of 2. The third area relates to the important new progress in the understanding of the biological mechanisms involved in cellular ageing. The recent progress in the area of cellular biology has started to decode the complex mechanisms underlying cellular ageing. The important understanding of the phenomena of apoptose with the development of relevant biological models of the natural ageing process have anticipated future treatments and, eventually, the prophylactic treatment of specific pathologies of the elderly patient.     

Atlantic bluefin tuna: a novel multistock spatial model for assessing population biomass

Atlantic bluefin tuna (Thunnus thynnus) is considered to be overfished, but the status of its populations has been debated, partly because of uncertainties regarding the effects of mixing on fishing grounds. A better understanding of spatial structure and mixing may help fisheries managers to successfully rebuild populations to sustainable levels while maximizing catches. We formulate a new seasonally and spatially explicit fisheries model that is fitted to conventional and electronic tag data, historic catch-at-age reconstructions, and otolith microchemistry stock-composition data to improve the capacity to assess past, current, and future population sizes of Atlantic bluefin tuna. We apply the model to estimate spatial and temporal mixing of the eastern (Mediterranean) and western (Gulf of Mexico) populations, and to reconstruct abundances from 1950 to 2008. We show that western and eastern populations have been reduced to 17% and 33%, respectively, of 1950 spawning stock biomass levels. Overfishing to below the biomass that produces maximum sustainable yield occurred in the 1960s and the late 1990s for western and eastern populations, respectively. The model predicts that mixing depends on season, ontogeny, and location, and is highest in the western Atlantic. Assuming that future catches are zero, western and eastern populations are predicted to recover to levels at maximum sustainable yield by 2025 and 2015, respectively. However, the western population will not recover with catches of 1750 and 12,900 tonnes (the "rebuilding quotas") in the western and eastern Atlantic, respectively, with or without closures in the Gulf of Mexico. If future catches are double the rebuilding quotas, then rebuilding of both populations will be compromised. If fishing were to continue in the eastern Atlantic at the unregulated levels of 2007, both stocks would continue to decline. Since populations mix on North Atlantic foraging grounds, successful rebuilding policies will benefit from trans-Atlantic cooperation.     

Novel 3D culture system for study of cardiac myocyte development

Insufficient myocardial repair after pathological processes contributes to cardiovascular disease, which is a major health concern. Understanding the molecular mechanisms that regulate the proliferation and differentiation of cardiac myocytes will aid in designing therapies for myocardial repair. Models are needed to delineate these molecular mechanisms. Here we report the development of a model system that recapitulates many aspects of cardiac myocyte differentiation that occur during early cardiac development. A key component of this model is a novel three-dimensional tubular scaffold engineered from aligned type I collagen strands. In this model embryonic ventricular myocytes undergo a transition from a hyperplastic to a quiescent phenotype, display significant myofibrillogenesis, and form critical cell-cell connections. In addition, embryonic cardiac myocytes grown on the tubular substrate have an aligned phenotype that closely resembles in vivo neonatal ventricular myocytes. We propose that embryonic cardiac myocytes grown on the tube substrate develop into neonatal cardiac myocytes via normal in vivo mechanisms. This model will aid in the elucidation of the molecular mechanisms that regulate cardiac myocyte proliferation and differentiation, which will provide important insights into myocardial development.     

D‐galactose‐induced cardiac ageing: A review of model establishment and potential interventions

Cardiovascular disease (CVD) is highly prevalent in an ageing society. The increased incidence and mortality rates of CVD are global issues endangering human health. There is an urgent requirement for understanding the aetiology and pathogenesis of CVD and developing possible interventions for preventing CVD in ageing hearts. It is necessary to select appropriate models and treatment methods. The D‐galactose‐induced cardiac ageing model possesses the advantages of low mortality, short time and low cost and has been increasingly used in the study of cardiovascular diseases in recent years. Therefore, understanding the latest progress in D‐galactose‐induced cardiac ageing is valuable. This review highlights the recent progress and potential therapeutic interventions used in D‐galactose‐induced cardiac ageing in recent years by providing a comprehensive summary of D‐galactose‐induced cardiac ageing in vivo and in vitro. This review may serve as reference literature for future research on age‐related heart diseases.     

Climate Change Impacts on the Future Distribution of Date Palms: A Modeling Exercise Using CLIMEX

Climate is changing and, as a consequence, some areas that are climatically suitable for date palm (Phoenix dactylifera L.) cultivation at the present time will become unsuitable in the future. In contrast, some areas that are unsuitable under the current climate will become suitable in the future. Consequently, countries that are dependent on date fruit export will experience economic decline, while other countries’ economies could improve. Knowledge of the likely potential distribution of this economically important crop under current and future climate scenarios will be useful in planning better strategies to manage such issues. This study used CLIMEX to estimate potential date palm distribution under current and future climate models by using one emission scenario (A2) with two different global climate models (GCMs), CSIRO-Mk3.0 (CS) and MIROC-H (MR). The results indicate that in North Africa, many areas with a suitable climate for this species are projected to become climatically unsuitable by 2100. In North and South America, locations such as south-eastern Bolivia and northern Venezuela will become climatically more suitable. By 2070, Saudi Arabia, Iraq and western Iran are projected to have a reduction in climate suitability. The results indicate that cold and dry stresses will play an important role in date palm distribution in the future. These results can inform strategic planning by government and agricultural organizations by identifying new areas in which to cultivate this economically important crop in the future and those areas that will need greater attention due to becoming marginal regions for continued date palm cultivation.     

用于药物评价的体外心脏组织模型研究进展

候选药物对心脏的毒副作用是其在开发过程中被淘汰的重要原因之一.传统药物评价所采用的动物模型存在种属差异、成本高、效率低等缺陷.因此,近年来随着干细胞和生物打印等技术的快速发展,体外心脏组织模型的构建受到了越来越多地关注.本文追踪体外心脏模型构建的起源与发展,综述模型所利用的心肌细胞来源以及二维、三维模型构建的相关技术与方法,着重阐述心肌组织模型血管化的重要性及研究进展,并对该领域未来的发展方向进行展望,以期为体外心肌组织模型在药物评价方面的研究和应用提供新思路.