Stem-cell-based therapy and lessons from the heart

The potential usefulness of human embryonic stem cells for therapy derives from their ability to form any cell in the body. This potential has been used to justify intensive research despite some ethical concerns. In parallel, scientists have searched for adult stem cells that can be used as an alternative to embryonic cells, and, for the heart at least, these efforts have led to promising results. However, most adult cardiomyocytes are unable to divide and form new cardiomyocytes and would therefore be unable to replace those lost as a result of disease. Basic questions--for example, whether cardiomyocyte replacement or alternatives, such as providing the damaged heart with new blood vessels or growth factors to activate resident stem cells, are the best approach--remain to be fully addressed. Despite this, preclinical studies on cardiomyocyte transplantation in animals and the first clinical trials with adult stem cells have recently been published with mixed results.     

Arc-parallel flow in the mantle wedge beneath Costa Rica and Nicaragua

Resolving flow geometry in the mantle wedge is central to understanding the thermal and chemical structure of subduction zones, subducting plate dehydration, and melting that leads to arc volcanism, which can threaten large populations and alter climate through gas and particle emission. Here we show that isotope geochemistry and seismic velocity anisotropy provide strong evidence for trench-parallel flow in the mantle wedge beneath Costa Rica and Nicaragua. This finding contradicts classical models, which predict trench-normal flow owing to the overlying wedge mantle being dragged downwards by the subducting plate. The isotopic signature of central Costa Rican volcanic rocks is not consistent with its derivation from the mantle wedge or eroded fore-arc complexes but instead from seamounts of the Galapagos hotspot track on the subducting Cocos plate. This isotopic signature decreases continuously from central Costa Rica to northwestern Nicaragua. As the age of the isotopic signature beneath Costa Rica can be constrained and its transport distance is known, minimum northwestward flow rates can be estimated (63-190 mm yr(-1)) and are comparable to the magnitude of subducting Cocos plate motion (approximately 85 mm yr(-1)). Trench-parallel flow needs to be taken into account in models evaluating thermal and chemical structure and melt generation in subduction zones.     

The genome of the model beetle and pest Tribolium castaneum

Tribolium castaneum is a member of the most species-rich eukaryotic order, a powerful model organism for the study of generalized insect development, and an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved the ability to interact with a diverse chemical environment, as shown by large expansions in odorant and gustatory receptors, as well as P450 and other detoxification enzymes. Development in Tribolium is more representative of other insects than is Drosophila, a fact reflected in gene content and function. For example, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, some being expressed in the growth zone crucial for axial elongation in short-germ development. Systemic RNA interference in T. castaneum functions differently from that in Caenorhabditis elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.     

Ancient, highly heterogeneous mantle beneath Gakkel ridge, Arctic Ocean

The Earth's mantle beneath ocean ridges is widely thought to be depleted by previous melt extraction, but well homogenized by convective stirring. This inference of homogeneity has been complicated by the occurrence of portions enriched in incompatible elements. Here we show that some refractory abyssal peridotites from the ultraslow-spreading Gakkel ridge (Arctic Ocean) have very depleted 187Os/188Os ratios with model ages up to 2 billion years, implying the long-term preservation of refractory domains in the asthenospheric mantle rather than their erasure by mantle convection. The refractory domains would not be sampled by mid-ocean-ridge basalts because they contribute little to the genesis of magmas. We thus suggest that the upwelling mantle beneath mid-ocean ridges is highly heterogeneous, which makes it difficult to constrain its composition by mid-ocean-ridge basalts alone. Furthermore, the existence of ancient domains in oceanic mantle suggests that using osmium model ages to constrain the evolution of continental lithosphere should be approached with caution.     

圆环上以径向函数为符号的Toeplitz算子和Hankel算子

本文研究了圆环内以径向函数为符号的Ｔｏｐｌｉｔｚ,算子和Ｈａｎｋｅｌ算子的有界性,紧性以及谱的一些性质。     

非离子表面活性剂Tween-80存在下5-Br-PADAP分光光度法同时测定微量Cu(Ⅱ)和Fe(Ⅲ)

在pH 3.50酸性介质中,Cu(Ⅱ)和Fe(Ⅲ)在非离子表面活性剂Tween-80存在下与5-Br-PADAP生成有色配合物.有色配合物最大吸收波长都位于570 nm处;表观摩尔吸光系数分别为7.96×104 L·mol-1·cm-1和6.30×104 L·mol-1·cm-1;Cu(Ⅱ)在0～13 μg/25ml,Fe(Ⅲ)在0～18 μg/25ml范围内符合比耳定律.用拟定的方法测定了铝片和水样中的Cu(Ⅱ)和Fe(Ⅲ),结果令人满意.     

Antitumoral effects of 9-cis retinoic acid in adrenocortical cancer

The currently available medical treatment options of adrenocortical cancer (ACC) are limited. In our previous meta-analysis of adrenocortical tumor genomics data, ACC was associated with reduced retinoic acid production and retinoid X receptor-mediated signaling. Our objective has been to study the potential antitumoral effects of 9-cis retinoic acid (9-cisRA) on the ACC cell line NCI-H295R and in a xenograft model. Cell proliferation, hormone secretion, and gene expression have been studied in the NCI-H295R cell line. A complex bioinformatics approach involving pathway and network analysis has been performed. Selected genes have been validated by real-time qRT-PCR. Athymic nude mice xenografted with NCI-H295R have been used in a pilot in vivo xenograft model. 9-cisRA significantly decreased cell viability and steroid hormone secretion in a concentration- and time-dependent manner in the NCI-H295R cell line. Four major molecular pathways have been identified by the analysis of gene expression data. Ten genes have been successfully validated involved in: (1) steroid hormone secretion (HSD3B1, HSD3B2), (2) retinoic acid signaling (ABCA1, ABCG1, HMGCR), (3) cell-cycle damage (GADD45A, CCNE2, UHRF1), and the (4) immune response (MAP2K6, IL1R2). 9-cisRA appears to directly regulate the cell cycle by network analysis. 9-cisRA also reduced tumor growth in the in vivo xenograft model. In conclusion, 9-cisRA might represent a promising new candidate in the treatment of hormone-secreting adrenal tumors and adrenocortical cancer.     

Molecular dialogue between the human gut microbiota and the host: a Lactobacillus and Bifidobacterium perspective

The human gut represents a highly complex ecosystem, which is densely colonized by a myriad of microorganisms that influence the physiology, immune function and health status of the host. Among the many members of the human gut microbiota, there are microorganisms that have co-evolved with their host and that are believed to exert health-promoting or probiotic effects. Probiotic bacteria isolated from the gut and other environments are commercially exploited, and although there is a growing list of health benefits provided by the consumption of such probiotics, their precise mechanisms of action have essentially remained elusive. Genomics approaches have provided exciting new opportunities for the identification of probiotic effector molecules that elicit specific responses to influence the physiology and immune function of their human host. In this review, we describe the current understanding of the intriguing relationships that exist between the human gut and key members of the gut microbiota such as bifidobacteria and lactobacilli, discussed here as prototypical groups of probiotic microorganisms.     

Epigenetic dysregulation of brainstem nuclei in the pathogenesis of Alzheimer’s disease: looking in the correct place at the right time?

Even though the etiology of Alzheimer’s disease (AD) remains unknown, it is suggested that an interplay among genetic, epigenetic and environmental factors is involved. An increasing body of evidence pinpoints that dysregulation in the epigenetic machinery plays a role in AD. Recent developments in genomic technologies have allowed for high throughput interrogation of the epigenome, and epigenome-wide association studies have already identified unique epigenetic signatures for AD in the cortex. Considerable evidence suggests that early dysregulation in the brainstem, more specifically in the raphe nuclei and the locus coeruleus, accounts for the most incipient, non-cognitive symptomatology, indicating a potential causal relationship with the pathogenesis of AD. Here we review the advancements in epigenomic technologies and their application to the AD research field, particularly with relevance to the brainstem. In this respect, we propose the assessment of epigenetic signatures in the brainstem as the cornerstone of interrogating causality in AD. Understanding how epigenetic dysregulation in the brainstem contributes to AD susceptibility could be of pivotal importance for understanding the etiology of the disease and for the development of novel diagnostic and therapeutic strategies.     

Defective germinal center B-cell response and reduced arthritic pathology in microRNA-29a-deficient mice

MicroRNA (miR) are short non-coding RNA sequences of 19–24 nucleotides that regulate gene expression by binding to mRNA target sequences. The miR-29 family of miR (miR-29a, b-1, b-2 and c) is a key player in T-cell differentiation and effector function, with deficiency causing thymic involution and a more inflammatory T-cell profile. However, the relative roles of different miR-29 family members in these processes have not been dissected. We studied the immunological role of the individual members of the miR-29 family using mice deficient for miR-29a/b-1 or miR-29b-2/c in homeostasis and during collagen-induced arthritis. We found a definitive hierarchy of immunological function, with the strong phenotype of miR-29a-deficiency in thymic involution and T-cell activation being reduced or absent in miR-29c-deficient mice. Strikingly, despite elevating the Th1 and Th17 responses, loss of miR-29a conferred near-complete protection from collagen-induced arthritis (CIA), with profound defects in B-cell proliferation and antibody production. Our results identify the hierarchical structure of the miR-29 family in T-cell biology, and identify miR-29a in B cells as a potential therapeutic target in arthritis.