Perceptions of palliative care in a lower middle-income Muslim country: A qualitative study of health care professionals, bereaved families and communities.

Background:: Palliative care has been successfully integrated into many Muslim-majority countries, most frequently in urbanised areas with developed health care systems. Less is known as to how the concept of palliative care is perceived by Muslim populations and health workers in rural, resource-limited contexts.

Aim:: This study seeks to explore whether the principles of palliative care are congruent with the perspectives of health professionals, families and communities in rural areas of the Islamic Republic of Mauritania, in West Africa.

Pro-apoptotic activity of mBNIP-21 depends on its BNIP-2 and Cdc42GAP homology (BCH) domain and is enhanced by coxsackievirus B3 infection.

Our previous study reported that mouse BNIP-21 (mBNIP-21) induces apoptosis through a mitochondria-dependent pathway. To map the functional domains of mBNIP-21, we performed mutational analyses and demonstrated that the BNIP-2 and Cdc42GAP homology (BCH) domain is required for apoptosis induction by mBNIP-21 targeting the mitochondria and inducing cytochrome c release. This pro-apoptotic activity was enhanced by coxsackievirus infection.

MicroRNA: An emerging therapeutic target and intervention tool.

MicroRNAs (miRNAs) are a class of short non-coding RNAs with posttranscriptional regulatory functions. To date, more than 600 human miRNAs have been experimentally identified, and estimated to regulate more than one third of cellular messenger RNAs. Accumulating evidence has linked the dysregulated expression patterns of miRNAs to a variety of diseases, such as cancer, neurodegenerative diseases, cardiovascular diseases and viral infections.

ERK MAP kinase-activated Arf6 trafficking directs coxsackievirus type B3 into an unproductive compartment during virus host-cell entry.

Clathrin- and caveolae-mediated endocytosis have been implicated in the productive entry of many viruses into host cells. ADP-ribosylation factor 6 (Arf6)-dependent endocytosis is another endocytosis pathway that traffics from the cell surface and it is the only Arf that traffics at the plasma membrane. However, little is known about Arf6-dependent trafficking during virus entry.

CXCL10 inhibits viral replication through recruitment of natural killer cells in coxsackievirus B3-induced myocarditis.

Coxsackievirus (CV)B3 is the primary cause of viral myocarditis. We previously observed CXC chemokine ligand 10 (CXCL10) upregulation in the myocardium early in infection. However, the impact of CXCL10 in CVB3-induced myocarditis is unknown.

MicroRNAs-based therapeutic strategy for virally induced diseases.

MicroRNAs (miRNAs) are endogenous, short, double-stranded and noncoding RNA molecules that have been identified in a variety of organisms and certain viruses. This group of new molecules is transcribed mainly from the introns and/or exons or intergenic regions and plays important regulatory roles in development and gene expression. Mature miRNAs are typically 20-24 nucleotides in length and regulate target mRNAs post transcriptionally by interactions with partially mismatched sequences in the 3'untraslated regions of these messengers.

Antisense DNA and RNA agents against picornaviruses.

Anti-picornaviral antisense agents are part of a broader group of nucleic acid-based molecules developed for sequence-specific inhibition of translation and/or transcription of the target sequence through induced nuclease activity or physical hindrance. Three types of nucleic acid-based gene silencing molecules can be distinguished, including DNA-base antisense oligonucleotides (ASO), nucleic acid enzymes (ribozyme and DNAzyme) and double-stranded small interfering RNA (siRNA or microRNA). These antisense DNA and RNA molecules have been widely studied for gene functional studies and therapeutic purposes.

Focal adhesion kinase mediates the interferon-gamma-inducible GTPase-induced phosphatidylinositol 3-kinase/Akt survival pathway and further initiates a positive feedback loop of NF-kappaB activation.

Interferon-gamma-inducible GTPase (IGTP) expression is upregulated in coxsackievirus B3 (CVB3)-infected murine heart and inhibits CVB3-induced apoptosis through activation of the PI3 kinase/Akt pathway. However, the mechanism of this pathway activation is unknown. In this study, using doxcycycline-inducible Tet-On HeLa cells that overexpress IGTP, we have demonstrated that focal adhesion kinase (FAK) is phosphorylated in response to IGTP expression and that transfection of the Tet-On HeLa cells with a dominant negative FAK (FRNK) blocks Akt activation.

Coxsackievirus B3 proteases 2A and 3C induce apoptotic cell death through mitochondrial injury and cleavage of eIF4GI but not DAP5/p97/NAT1.

By transfection of Coxsackievirus B3 (CVB3) individual protease gene into HeLa cells, we demonstrated that 2A(pro) and 3C(pro) induced apoptosis through multiple converging pathways. Firstly, both 2A(pro) and 3C(pro) induced caspase-8-mediated activation of caspase-3 and dramatically reduced cell viability. Secondly, they both activated the intrinsic mitochondria-mediated apoptosis pathway leading to cytochrome c release from mitochondria and activation of caspase-9.

Nucleic-acid-based antiviral agents against positive single-stranded RNA viruses.

Positive single-stranded RNA viruses constitute a broad and prevalent group of pathogens that threaten human health and life worldwide. While effective vaccines have been developed for some, such as poliovirus and hepatitis A, others such as coxsackievirus, severe acute respiratory syndrome coronavirus (SARS-CoV) and West Nile virus have no accredited drug treatments. Antisense technologies, which encompass small interfering RNA, antisense oligonucleotides, ribozymes and their chemically modified analogs, involve small sequence-specific nucleic-acid-based molecules that inhibit viral replication at the level of translation.

Mitogenic activity of Epstein-Barr virus-encoded BARF1 protein.

We previously reported that BARF1 gene has either an immortalizing effect, when expressed in primary primate epithelial cells, or a malignant transforming activity, when expressed in established and nontumoral rodent fibroblast or human B-cell lines. As predicted from sequence analysis, we found that BARF1 coded protein can be secreted from different cell lines, among them BARF1-transfected Balb/c3T3 rodent fibroblasts. Thus, as an initial step to clarify BARF1 oncogenic functions, we investigated whether the secreted form of BARF1 protein can activate the cell cycle as a growth factor.

The AT-hook protein D1 is essential for Drosophila melanogaster development and is implicated in position-effect variegation.

We have analyzed the expression pattern of the D1 gene and the localization of its product, the AT hook-bearing nonhistone chromosomal protein D1, during Drosophila melanogaster development. D1 mRNAs and protein are maternally contributed, and the protein localizes to discrete foci on the chromosomes of early embryos. These foci correspond to 1.