E-Health Technologies in Attainment of the Millennium Development Goals for Africa Healthcare System

The challenge of quality and equitable health services provisioning in Africa is daunting. Advances in e-health technologies hold great potential to revolutionalize health systems in Africa. This paper examines the African health systems challenges and the potential in e-health technologies in enabling the attainment of the African health Millennium Development Goals. An e-health research, innovation and partnership strategy is proposed towards this end. Some implications are posited and conclusion drawn

The Evolutionary Origin of the Runx/CBFbeta Transcription Factors – Studies of the Most Basal Metazoans

BACKGROUND. Members of the Runx family of transcriptional regulators, which bind DNA as heterodimers with CBFβ, are known to play critical roles in embryonic development in many triploblastic animals such as mammals and insects. They are known to regulate basic developmental processes such as cell fate determination and cellular potency in multiple stem-cell types, including the sensory nerve cell progenitors of ganglia in mammals. RESULTS. In this study, we detect and characterize the hitherto unexplored Runx/CBFβ genes of cnidarians and sponges, two basal animal lineages that are well known for their extensive regenerative capacity. Comparative structural modeling indicates that the Runx-CBFβ-DNA complex from most cnidarians and sponges is highly similar to that found in humans, with changes in the residues involved in Runx-CBFβ dimerization in either of the proteins mirrored by compensatory changes in the binding partner. In situ hybridization studies reveal that Nematostella Runx and CBFβ are expressed predominantly in small isolated foci at the base of the ectoderm of the tentacles in adult animals, possibly representing neurons or their progenitors. CONCLUSION. These results reveal that Runx and CBFβ likely functioned together to regulate transcription in the common ancestor of all metazoans, and the structure of the Runx-CBFβ-DNA complex has remained extremely conserved since the human-sponge divergence. The expression data suggest a hypothesis that these genes may have played a role in nerve cell differentiation or maintenance in the common ancestor of cnidarians and bilaterians.National Science Foundation (IBN-0212773, FP-91656101-0); Boston University SPRInG (20-202-8103-9); Israel Science Foundation (825/07

Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs

Activation of naive CD8+ T cells with antigen induces their differentiation into effector cytolytic T lymphocytes (CTLs). CTLs lyse infected or aberrant target cells by exocytosis of lytic granules containing the pore-forming protein perforin and a family of proteases termed granzymes. We show that effector CTL differentiation occurs in two sequential phases in vitro, characterized by early induction of T-bet and late induction of Eomesodermin (Eomes), T-box transcription factors that regulate the early and late phases of interferon (IFN) γ expression, respectively. In addition, we demonstrate a critical role for the transcription factor Runx3 in CTL differentiation. Runx3 regulates Eomes expression as well as expression of three cardinal markers of the effector CTL program: IFN-γ, perforin, and granzyme B. Our data point to the existence of an elaborate transcriptional network in which Runx3 initially induces and then cooperates with T-box transcription factors to regulate gene transcription in differentiating CTLs

The evolutionary origin of the Runx/CBFbeta transcription factors – Studies of the most basal metazoans

Abstract Background Members of the Runx family of transcriptional regulators, which bind DNA as heterodimers with CBFβ, are known to play critical roles in embryonic development in many triploblastic animals such as mammals and insects. They are known to regulate basic developmental processes such as cell fate determination and cellular potency in multiple stem-cell types, including the sensory nerve cell progenitors of ganglia in mammals. Results In this study, we detect and characterize the hitherto unexplored Runx/CBFβ genes of cnidarians and sponges, two basal animal lineages that are well known for their extensive regenerative capacity. Comparative structural modeling indicates that the Runx-CBFβ-DNA complex from most cnidarians and sponges is highly similar to that found in humans, with changes in the residues involved in Runx-CBFβ dimerization in either of the proteins mirrored by compensatory changes in the binding partner. In situ hybridization studies reveal that Nematostella Runx and CBFβ are expressed predominantly in small isolated foci at the base of the ectoderm of the tentacles in adult animals, possibly representing neurons or their progenitors. Conclusion These results reveal that Runx and CBFβ likely functioned together to regulate transcription in the common ancestor of all metazoans, and the structure of the Runx-CBFβ-DNA complex has remained extremely conserved since the human-sponge divergence. The expression data suggest a hypothesis that these genes may have played a role in nerve cell differentiation or maintenance in the common ancestor of cnidarians and bilaterians.</p

The evolutionary origin of the Runx/CBFbeta transcription factors – Studies of the most basal metazoans-5

the ORF (exons 1–3, which contain the Runt domain) were used to characterize the spatial expression of Runx in adult . Similar results were obtained using a longer probe corresponding to the entire transcript (not shown). Labeled anti-sense probes detect expression in the oral region of the anemones, particularly in the ectoderm of the tentacle tips (animal on left). No specific staining was observed using sense-strand probes (animal on right). While expression was always limited to the tentacle and head region there was some background staining that varied between individual animals. Note that the dark color in the mouth of the animal depicted in panel B (arrowhead) does not represent Runx expression, since it is not detected in sections of this region. The arrowhead in Panel C reveals the strong expression at the tentacle tips. These panels show ectodermal expression of in the tentacles as seen in cryostat sections of anemones after whole mount hybridization. Low magnification micrograph of a section through the head and tentacles, revealing general architecture as well as the location of the enlarged micrographs in E and F. Bar = 100 μm Expression of in the ectoderm of the tentacles, Bars in E and F = 50 μm, in G = 20 μm, A thin section of a tentacle from Nematostella, stained with Methylene Blue. Numerous spirocysts (Sp) and several nematocysts (N) can be observed, as can darkly and heterogeneously stained gland cells (G) found towards the apical part of the ectoderm. The elongated cells (S) are probably sensory cells []. The mesoglea (Mes) is schematically marked by a dashed line. Bar = 10 μm. Expression of Nv-Runx in scattered cells in the ectoderm of the body wall (arrowhead). Bar = 20 μm.<p><b>Copyright information:</b></p><p>Taken from "The evolutionary origin of the Runx/CBFbeta transcription factors – Studies of the most basal metazoans"</p><p>http://www.biomedcentral.com/1471-2148/8/228</p><p>BMC Evolutionary Biology 2008;8():228-228.</p><p>Published online 5 Aug 2008</p><p>PMCID:PMC2527000.</p><p></p

Positional differences of axon growth rates between sensory neurons encoded by runx3

The formation of functional connectivity in the nervous system is governed by axon guidance that instructs nerve growth and branching during development, implying a similarity between neuronal subtypes in terms of nerve extension. We demonstrate the molecular mechanism of another layer of complexity in vertebrates by defining a transcriptional program underlying growth differences between positionally different neurons. The rate of axon extension of the early subset of embryonic dorsal root ganglion sensory neurons is encoded in neurons at different axial levels. This code is determined by a segmental pattern of axial levels of Runx family transcription factor Runx3. Runx3 in turn determines transcription levels of genes encoding cytoskeletal proteins involved in axon extension, including Rock1 and Rock2 which have ongoing activities determining axon growth in early sensory neurons and blocking Rock activity reverses axon extension deficits of Runx3−/− neurons. Thus, Runx3 acts to regulate positional differences in axon extension properties apparently without affecting nerve guidance and branching, a principle that could be relevant to other parts of the nervous system.Fil: Lallemend, Francois. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Sterzenbach, Ulrich. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Hadjab Lallemend, Saida. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Aquino, Jorge Benjamin. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Castelo Branco, Goncalo. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Sinha, Indranil. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Villaescusa, J. Carlos. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Levanon, Ditsa. The Weizmann Institute of Science; IsraelFil: Wang, Yiqiao. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Franck, Marina C. M.. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Kharchenko, Olga. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Adameyko, Igor. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Linnarsson, Sten. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Groner, Yoram. The Weizmann Institute of Science; IsraelFil: Turner, Eric. Seattle Children's Research Institute; Estados UnidosFil: Ernfors, Patrik. Karolinska Huddinge Hospital. Karolinska Institutet; Sueci

The evolutionary origin of the Runx/CBFbeta transcription factors – Studies of the most basal metazoans-4

Ion (including tentacle bases), body column, and physa. Reverse-transcription (RT) PCR was performed on an equal amount of total RNA extracted from each of the four body regions. An equivalent fraction of the amplification reaction was visualized on an agarose gel. Using this assay, expression was detected in the tentacles, and to a lesser extent in the head/pharyngeal region, but not in the column or physa. As a positive control, actin was found to be expressed at high levels in all four body regions.<p><b>Copyright information:</b></p><p>Taken from "The evolutionary origin of the Runx/CBFbeta transcription factors – Studies of the most basal metazoans"</p><p>http://www.biomedcentral.com/1471-2148/8/228</p><p>BMC Evolutionary Biology 2008;8():228-228.</p><p>Published online 5 Aug 2008</p><p>PMCID:PMC2527000.</p><p></p