Horizontal gene transfer of epigenetic machinery and evolution of parasitism in the malaria parasite Plasmodium falciparum and other apicomplexans

Background The acquisition of complex transcriptional regulatory abilities and epigenetic machinery facilitated the transition of the ancestor of apicomplexans from a free-living organism to an obligate parasite. The ability to control sophisticated gene expression patterns enabled these ancient organisms to evolve several differentiated forms, invade multiple hosts and evade host immunity. How these abilities were acquired remains an outstanding question in protistan biology. Results In this work, we study SET domain bearing genes that are implicated in mediating immune evasion, invasion and cytoadhesion pathways of modern apicomplexans, including malaria parasites. We provide the first conclusive evidence of a horizontal gene transfer of a Histone H4 Lysine 20 (H4K20) modifier, Set8, from an animal host to the ancestor of apicomplexans. Set8 is known to contribute to the coordinated expression of genes involved in immune evasion in modern apicomplexans. We also show the likely transfer of a H3K36 methyltransferase (Ashr3 from plants), possibly derived from algal endosymbionts. These transfers appear to date to the transition from free-living organisms to parasitism and coincide with the proposed horizontal acquisition of cytoadhesion domains, the O-glycosyltransferase that modifies these domains, and the primary family of transcription factors found in apicomplexan parasites. Notably, phylogenetic support for these conclusions is robust and the genes clearly are dissimilar to SET sequences found in the closely related parasite Perkinsus marinus, and in ciliates, the nearest free-living organisms with complete genome sequences available. Conclusions Animal and plant sources of epigenetic machinery provide new insights into the evolution of parasitism in apicomplexans. Along with the horizontal transfer of cytoadhesive domains, O-linked glycosylation and key transcription factors, the acquisition of SET domain methyltransferases marks a key transitional event in the evolution to parasitism in this important protozoan lineage

Enabling access to new WHO essential medicines: the case for nicotine replacement therapies

Nicotine replacement therapies (NRT) are powerful tools for the successful treatment of nicotine addiction and tobacco use. The medicines are clinically effective, supported by the Framework Convention on Tobacco Control, and are now World Health Organization-approved essential medicines. Enabling global access to NRT remains a challenge given ongoing confusion and misperceptions about their efficacy, cost-effectiveness, and availability with respect to other tobacco control and public health opportunities. In this commentary, we review existing evidence and guidelines to make the case for global access to NRT highlighting the smoker's right to access treatment to sensibly address nicotine addiction

A Student-Led Campaign to Help Tackle Neglected Tropical Diseases

The authors propose that innovative student-led campaigns to address neglected diseases can and do make a practical difference

On Essentiality and the World Health Organization's Model List of Essential Medicines

BackgroundIn 1977 the World Health Organization created its first Model List of Essential Medicines—a list designed to aid countries in determining which medicines to prioritize on their National Essential Medicines Lists. In classifying drugs as “essential,” the World Health Organization has historically stressed drugs' ability to meet priority health needs of populations and cost.ObjectivesIn this paper we trace the fluctuations in the application of cost and priority status of disease as criteria for essential medicines throughout the reports published by the WHO Expert Committee on Selection and Use of Essential Medicines since 1977.MethodsWe analyzed essential medicines lists published on the World Health Organization website since 1977 for trends in criteria concerning cost and priority status of disease. Where, available, analyzed the World Health Organization Expert Committee analysis rationalizing why certain medicines were or were not added and were or were not removed.ResultsThe application of the criteria of cost and priority status of essential medicines has fluctuated dramatically over the years.ConclusionsThe definition of essential medicines has shifted and now necessitates a new consensus on normative definitions and criteria. A more standardized and transparent set of procedures for choosing essential medicines is required

Young professionals for health development: the Kenyan experience in combating non-communicable diseases

Young individuals (below 35 years) comprise an estimated 60% of the global population. Not only are these individuals currently experiencing chronic, non-communicable diseases (NCDs), either living with or at risk for these conditions, but will also experience the long-term repercussions of the current NCD policy implementations. It is thus imperative that they meaningfully contribute to the global discourse and responses for NCDs at the local level. Here, we profile one example of meaningful engagement: the Young Professionals Chronic Disease Network (YPCDN). The YPCDN is a global online network that provides a platform for young professionals to deliberate new and innovative methods of approaching the NCD challenges facing our societies. We provide a case study of the 2-year experiences of a country chapter (Kenya) of the YPCDN to demonstrate the significance and impact of emerging leaders in addressing the new global health agenda of the 21st century

Misalignment between perceptions and actual global burden of disease: evidence from the US population

Significant funding of health programs in low-income countries comes from external sources, mainly private donors and national development agencies of high-income countries. How these external funds are allocated remains a subject of ongoing debate, as studies have revealed that external funding may misalign with the underlying disease burden. One determinant of the priorities set by both private donors and development agencies is the perceptions of populations living in high-income countries about which diseases are legitimate for global health intervention. While research has been conducted on the priorities expressed by recipient communities, relatively less has been done to assess those of the donating country. To investigate people's beliefs about the disease burden in high-income countries, we compared publicly available data from U.S. surveys of people's perceptions of the leading causes of death in developing countries against measures of the actual disease burden from the World Health Organization. We found little correlation between the U.S. public's perception and the actual disease burden, measured as either mortality or disability-adjusted life years. While there is potential for reverse causality, so that donor programs drive public perceptions, these findings suggest that increasing the general population's awareness of the true global disease burden could help better align global health funding with population health needs

Promotion of access to essential medicines for Non-Communicable Diseases: Practical implications of the UN Political Declaration

Access to medicines and vaccines to prevent and treat non-communicable diseases (NCDs) is unacceptably low worldwide. In the 2011 UN political declaration on the prevention and control of NCDs, heads of government made several commitments related to access to essential medicines, technologies, and vaccines for such diseases. 30 years of experience with policies for essential medicines and 10 years of scaling up of HIV treatment have provided the knowledge needed to address barriers to long-term effective treatment and prevention of NCDs. More medicines can be acquired within existing budgets with efficient selection, procurement, and use of generic medicines. Furthermore, low-income and middle-income countries need to increase mobilisation of domestic resources to cater for the many patients with NCDs who do not have access to treatment. Existing initiatives for HIV treatment offer useful lessons that can enhance access to pharmaceutical management of NCDs and improve adherence to long-term treatment of chronic illness; policy makers should also address unacceptable inequities in access to controlled opioid analgesics. In addition to off-patent medicines, governments can promote access to new and future on-patent medicinal products through coherent and equitable health and trade policies, particularly those for intellectual property. Frequent conflicts of interest need to be identified and managed, and indicators and targets for access to NCD medicines should be used to monitor progress. Only with these approaches can a difference be made to the lives of hundreds of millions of current and future patients with NCDs

Upregulation of ASCL1 and inhibition of Notch signaling pathway characterize progressive astrocytoma

Astrocytoma is the most common type of brain cancer constituting more than half of all brain tumors. With an aim to identify markers describing astrocytoma progression, we have carried out microarray analysis of astrocytoma samples of different grades using cDNA microarray containing 1152 cancer-specific genes. Data analysis identified several differentially regulated genes between normal brain tissue and astrocytoma as well as between grades II/III astrocytoma and glioblastoma multiforme (GBM; grade IV). We found several genes known to be involved in malignancy including Achaete-scute complex-like 1 (Drosophila) (ASCL1; Hash 1). As ASCL has been implicated in neuroendocrine, medullary thyroid and small-cell lung cancers, we chose to examine the role of ASCL1 in the astrocytoma development. Our data revealed that ASCL1 is overexpressed in progressive astrocytoma as evidenced by increased levels of ASCL1 transcripts in 85.71% (6/7) of grade II diffuse astrocytoma (DA), 90% (9/10) of grade III anaplastic astrocytoma (AA) and 87.5% (7/8) of secondary GBMs, while the majority of primary de novo GBMs expressed similar to or less than normal brain levels (66.67%; 8/12). ASCL1 upregulation in progressive astrocytoma is accompanied by inhibition of Notch signaling as seen by uninduced levels of HES1, a transcriptional target of Notch1, increased levels of HES6, a dominant-negative inhibitor of HES1-mediated repression of ASCL1, and increased levels of Notch ligand Delta1, which is capable of inhibiting Notch signaling by forming intracellular Notch ligand autonomous complexes. Our results imply that inhibition of Notch signaling may be an important early event in the development of grade II DA and subsequent progression to grade III AA and secondary GBM. Furthermore, ASCL1 appears to be a putative marker to distinguish primary GBM from secondary GBM