Analysis of conservation priorities of Iberoamerican cattle based on autosomal microsatellite markers

Background

Determining the value of livestock breeds is essential to define conservation priorities, manage genetic diversity and allocate funds. Within- and between-breed genetic diversity need to be assessed to preserve the highest intra-specific variability. Information on genetic diversity and risk status is still lacking for many Creole cattle breeds from the Americas, despite their distinct evolutionary trajectories and adaptation to extreme environmental conditions.

Methods

A comprehensive genetic analysis of 67 Iberoamerican cattle breeds was carried out with 19 FAO-recommended microsatellites to assess conservation priorities. Contributions to global diversity were investigated using alternative methods, with different weights given to the within- and between-breed components of genetic diversity. Information on Iberoamerican plus 15 worldwide cattle breeds was used to investigate the contribution of geographical breed groups to global genetic diversity.

Results

Overall, Creole cattle breeds showed a high level of genetic diversity with the highest level found in breeds admixed with zebu cattle, which were clearly differentiated from all other breeds. Within-breed kinships revealed seven highly inbred Creole breeds for which measures are needed to avoid further genetic erosion. However, if contribution to heterozygosity was the only criterion considered, some of these breeds had the lowest priority for conservation decisions. The Weitzman approach prioritized highly differentiated breeds, such as Guabalá, Romosinuano, Cr. Patagonico, Siboney and Caracú, while kinship-based methods prioritized mainly zebu-related breeds. With the combined approaches, breed ranking depended on the weights given to the within- and between-breed components of diversity. Overall, the Creole groups of breeds were generally assigned a higher priority for conservation than the European groups of breeds.

Conclusions

Conservation priorities differed significantly according to the weight given to within- and between-breed genetic diversity. Thus, when establishing conservation programs, it is necessary to also take into account other features. Creole cattle and local isolated breeds retain a high level of genetic diversity. The development of sustainable breeding and crossbreeding programs for Creole breeds, and the added value resulting from their products should be taken into consideration to ensure their long-term survival.     

CYP3A4 mediates growth of estrogen receptor-positive breast cancer cells in part by inducing nuclear translocation of phospho-Stat3 through biosynthesis of (±)-14,15-epoxyeicosatrienoic acid (EET)

CYP3A4 expression in breast cancer correlates with decreased overall survival, but the mechanisms are unknown. Cytochrome P450 gene profiling by RNAi silencing demonstrates that CYP3A or 2C8 gene expression is specifically required for growth of the breast cancer lines MCF7, T47D, and MDA-MB-231. CYP3A4 silencing blocks the cell cycle at the G(2)/M checkpoint and induces apoptosis in the MCF7 line, thereby inhibiting anchorage-dependent growth and survival. CYP3A4 was profiled for NADPH-dependent arachidonic acid (AA) metabolism and synthesized AA epoxygenase products (±)-8,9-, (±)-11,12-, and (±)-14,15-epoxyeicosatrienoic acid (EET) (total turnover of ～2 pmol/pmol CYP3A4/min) but not hydroxylase products (±)-15-, (±)-19-, or 20-hydroxyeicosatetraenoic acid. Furthermore, eicosanoid profiling revealed that MCF7 cells synthesize EETs in a CYP3A4-dependent manner. The (±)-14,15-EET regioisomer selectively rescues breast cancer cells from CYP3A4 silencing in a concentration-dependent fashion and promotes mitogenesis and anchorage-dependent cloning. Stat3 (Tyr-705) phosphorylation was inhibited by CYP3A4 silencing, providing a potential mechanism for CYP3A4 involvement in breast cancer cell growth. Silencing Stat3 blocks breast cancer cell growth and abrogates (±)-14,15-EET-induced proliferation, indicating a Stat3 requirement for (±)-14,15-EET-mediated cell growth. Although silencing of CYP3A4 reduces nuclear Tyr(P)-705-Stat3, (±)-14,15-EET restores this signaling process and promotes Tyr(P)-705-Stat3 translocation to the nucleus, suggesting that (±)-14,15-EET may be involved in an autocrine/paracrine pathway driving cell growth. These studies indicate that CYP3A4 is a highly active AA epoxygenase that promotes Stat3-mediated breast cancer cell growth in part through (±)-14,15-EET biosynthesis. Furthermore, these studies indicate an essential role for Stat3 as a mediator of epoxygenase activity in breast cancer.     

ArrayExpress: a public database of gene expression data at EBI

ArrayExpress is a public repository for microarray-based gene expression data, resulting from the implementation of the MAGE object model to ensure accurate data structuring and the MIAME standard, which defines the annotation requirements. ArrayExpress accepts data as MAGE-ML files for direct submissions or data from MIAMExpress, the MIAME compliant web-based annotation and submission tool of EBI. A team of curators supports the submission process, providing assistance in data annotation. Data retrieval is performed through a dedicated web interface. Relevant results may be exported to ExpressionProfiler, the EBI based expression analysis tool available online (http://www.ebi.ac.uk/arrayexpress).     

Prevalence and sequence comparison of Phyllodistomum folium from zebra mussel and from freshwater fish in the Ebro River

We utilised DNA analysis to detect the presence of the digenean Phyllodistomum folium in three cyprinid species, Scardinius erythrophthalmus, Cyprinus carpio and Rutilus rutilus. DNA sequencing of the region containing the genes ITS1-5.8S-ITS2 revealed 100% sequence identity between DNA from the sporocysts found in zebra mussels and DNA from adults located in the urinary system of 29 cyprinid fish. A second genetically different (variation=1.6%) sequence was observed in two samples from R. rutilus. In our opinion, the existence of a complex of species reported as P. folium is supported by recent genetic studies, including our own results. The overall prevalence of P. folium in mussels from the Ebro River was 4.67% in 2006, although during the summer months the rates frequently exceeded 10%.     

Conceptualizing a Genomics Software Institute (GSI)

Microbial ecology has been enhanced greatly by the ongoing 'omics revolution, bringing half the world's biomass and most of its biodiversity into analytical view for the first time; indeed, it feels almost like the invention of the microscope and the discovery of the new world at the same time. With major microbial ecology research efforts accumulating prodigious quantities of sequence, protein, and metabolite data, we are now poised to address environmental microbial research at macro scales, and to begin to characterize and understand the dimensions of microbial biodiversity on the planet. What is currently impeding progress is the need for a framework within which the research community can develop, exchange and discuss predictive ecosystem models that describe the biodiversity and functional interactions. Such a framework must encompass data and metadata transparency and interoperation; data and results validation, curation, and search; application programming interfaces for modeling and analysis tools; and human and technical processes and services necessary to ensure broad adoption. Here we discuss the need for focused community interaction to augment and deepen established community efforts, beginning with the Genomic Standards Consortium (GSC), to create a science-driven strategic plan for a Genomic Software Institute (GSI).     

Report of the 13(th) Genomic Standards Consortium Meeting, Shenzhen, China, March 4-7, 2012

This report details the outcome of the 13(th) Meeting of the Genomic Standards Consortium. The three-day conference was held at the Kingkey Palace Hotel, Shenzhen, China, on March 5-7, 2012, and was hosted by the Beijing Genomics Institute. The meeting, titled From Genomes to Interactions to Communities to Models, highlighted the role of data standards associated with genomic, metagenomic, and amplicon sequence data and the contextual information associated with the sample. To this end the meeting focused on genomic projects for animals, plants, fungi, and viruses; metagenomic studies in host-microbe interactions; and the dynamics of microbial communities. In addition, the meeting hosted a Genomic Observatories Network session, a Genomic Standards Consortium biodiversity working group session, and a Microbiology of the Built Environment session sponsored by the Alfred P. Sloan Foundation.     

Phospholipase C and Diacylglycerol Mediate Olfactory Responses to Amino Acids in the Main Olfactory Epithelium of an Amphibian

The semi-aquatic lifestyle of amphibians represents a unique opportunity to study the molecular driving forces involved in the transition of aquatic to terrestrial olfaction in vertebrates. Most amphibians have anatomically segregated main and vomeronasal olfactory systems, but at the cellular and molecular level the segregation differs from that found in mammals. We have recently shown that amino acid responses in the main olfactory epithelium (MOE) of larval Xenopus laevis segregate into a lateral and a medial processing stream, and that the former is part of a vomeronasal type 2 receptor expression zone in the MOE. We hypothesized that the lateral amino acid responses might be mediated via a vomeronasal-like transduction machinery. Here we report that amino acid-responsive receptor neurons in the lateral MOE employ a phospholipase C (PLC) and diacylglycerol-mediated transduction cascade that is independent of Ca²⁺ store depletion. Furthermore, we found that putative transient receptor potential (TRP) channel blockers inhibit most amino acid-evoked responses in the lateral MOE, suggesting that ion channels belonging to the TRP family may be involved in the signaling pathway. Our data show, for the first time, a widespread PLC- and diacylglycerol-dependent transduction cascade in the MOE of a vertebrate already possessing a vomeronasal organ.     

A dynamic multibody model of the physiological knee to predict internal loads during movement in gravitational field

Obtaining tibio-femoral (TF) contact forces, ligament deformations and loads during daily life motor tasks would be useful to better understand the aetiopathogenesis of knee joint diseases or the effects of ligament reconstruction and knee arthroplasty. However, methods to obtain this information are either too simplified or too computationally demanding to be used for clinical application. A multibody dynamic model of the lower limb reproducing knee joint contact surfaces and ligaments was developed on the basis of magnetic resonance imaging. Several clinically relevant conditions were simulated, including resistance to hyperextension, varus–valgus stability, anterior–posterior drawer, loaded squat movement. Quadriceps force, ligament deformations and loads, and TF contact forces were computed. During anterior drawer test the anterior cruciate ligament (ACL) was maximally loaded when the knee was extended (392 N) while the posterior cruciate ligament (PCL) was much more stressed during posterior drawer when the knee was flexed (319 N). The simulated loaded squat revealed that the anterior fibres of ACL become inactive after 60° of flexion in conjunction with PCL anterior bundle activation, while most components of the collateral ligaments exhibit limited length changes. Maximum quadriceps and TF forces achieved 3.2 and 4.2 body weight, respectively. The possibility to easily manage model parameters and the low computational cost of each simulation represent key points of the present project. The obtained results are consistent with in vivo measurements, suggesting that the model can be used to simulate complex and clinically relevant exercises.     

NEU3 sialidase strictly modulates GM3 levels in skeletal myoblasts C2C12 thus favoring their differentiation and protecting them from apoptosis

Membrane-bound sialidase NEU3, often referred to as the "ganglioside sialidase," has a critical regulatory function on the sialoglycosphingolipid pattern of the cell membrane, with an anti-apoptotic function, especially in cancer cells. Although other sialidases have been shown to be involved in skeletal muscle differentiation, the role of NEU3 had yet to be disclosed. Herein we report that NEU3 plays a key role in skeletal muscle differentiation by strictly modulating the ganglioside content of adjacent cells, with special regard to GM3. Induced down-regulation of NEU3 in murine C2C12 myoblasts, even when partial, totally inhibits their capability to differentiate by increasing the GM3 level above a critical point, which causes epidermal growth factor receptor inhibition (and ultimately its down-regulation) and an higher responsiveness of myoblasts to the apoptotic stimuli.     

An iron-deficient diet during development induces oxidative stress in relation to age and gender in Wistar rats

Iron is a trace element and a structural part of antioxidant enzymes, and its requirements vary according to age and gender. We hypothesized that iron deficiency (ID) leads to an increase in free radicals which mainly affect the brain, and the severity of damage would therefore be dependent on age and gender. Two groups of Wistar rats were evaluated evolutionarily: 100 rats (50 males; 50 females) with ID diet and 100 rats (50 males; 50 females) with standard diet. Both groups were offspring from mothers who were previously under the same dietary intervention. The ages studied roughly correspond to stages of human development: birth (0 postnatal day “PND” in rats), childhood (21 PND), early adolescence (42 PND), late adolescence (56 PND), and adulthood (70 PND). The following biomarkers in the brain, blood, and liver were analyzed: lipid peroxidation products (LPO), protein carbonyl content and activity of the antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase. It was demonstrated that ID subjects are born with high levels of LPO in the brain and low antioxidant activity, the damage being more severe in males. After birth, antioxidant defense focuses on the central level (brain) in ID females and on the peripheral level (blood and liver) in ID males. In two critical stages of development, birth and late adolescence, antioxidant protection is insufficient to counteract oxidative damage in ID subjects. Moreover, we observed that the variability of results in the literature on oxidative stress and ID comes from gender and age of the subjects under study. With this, we can establish patterns and exact moments to carry out studies or treatments.