role of next generation sequencing technologies in personalized medicine

Following the completion of the Human Genome Project in 2003, research in oncology has progressively focused on the sequencing of cancer genomes, with the aim of better understanding the genetic basis of oncogenesis and identifying actionable alterations. The development of next-generation-sequencing (NGS) techniques, commercially available since 2006, allowed for a cost- and time-effective sequencing of tumor DNA, leading to a "genomic era" of cancer research and treatment. NGS provided a significant step forward in Personalized Medicine (PM) by enabling the detection of somatic driver mutations, resistance mechanisms, quantification of mutational burden, germline mutations, which settled the foundation of a new approach in cancer care. In this chapter, we discuss the history, available techniques, and applications of NGS in oncology, with a particular referral to the PM approach and the emerging role of the research field of pharmacogenomics

The ActA polypeptides of Listeria ivanovii and Listeria monocytogenes harbor related binding sites for host microfilament proteins.

The surface-bound ActA polypeptide of the intracellular bacterial pathogen Listeria monocytogenes acts as a nucleator protein, generating the actin cytoskeleton around intracellularly motile bacteria. In this work, we examined the functional similarity of ActA from Listeria ivanovii (iActA) ATCC 19119 to its L. monocytogenes counterpart. The amino acid sequence of iActA predicts a molecular mass of 123 kDa and harbors eight proline-rich repeats. For functional analysis, various iActA derivatives and hybrid constructs of L. ivanovii and L. monocytogenes ActA polypeptides were transiently expressed in epithelial cells and examined for recruitment of host microfilament proteins by a mitochondrial targeting assay. As has been demonstrated with ActA, iActA also spontaneously inserted into the surface of mitochondria and induced recruitment of actin, alpha-actinin, and the vasodilator-stimulated phosphoprotein (VASP) to these subcellular organelles. By comparison of amino-terminally truncated iActA derivatives for their ability to recruit cytoskeletal proteins, a region essential for actin filament accumulation was identified between amino acid residues 290 and 325. Such derivatives, however, retained their ability to bind VASP. Replacement of the proline-rich repeats in ActA with those of iActA also resulted in VASP recruitment. Hence, despite the limited overall sequence homology between ActA and iActA, the two molecules consist of at least two similar domains: a highly positively charged N-terminal domain that is directly involved in actin filament recruitment and a proline-rich repeat region required for VASP binding

Delivery room management of very low birth weight infants in Germany, Austria and Switzerland - a comparison of protocols

<p>Abstract</p> <p>Background</p> <p>Surveys from the USA, Australia and Spain have shown significant inter-institutional variation in delivery room (DR) management of very low birth weight infants (VLBWI, < 1500 g) at birth, despite regularly updated international guidelines.</p> <p>Objective</p> <p>To investigate protocols for DR management of VLBWI in Germany, Austria and Switzerland and to compare these with the 2005 ILCOR guidelines.</p> <p>Methods</p> <p>DR management protocols were surveyed in a prospective, questionnaire-based survey in 2008. Results were compared between countries and between academic and non-academic units. Protocols were compared to the 2005 ILCOR guidelines.</p> <p>Results</p> <p>In total, 190/249 units (76%) replied. Protocols for DR management existed in 94% of units. Statistically significant differences between countries were found regarding provision of 24 hr in house neonatal service; presence of a designated resuscitation area; devices for respiratory support; use of pressure-controlled manual ventilation devices; volume control by respirator; and dosage of Surfactant. There were no statistically significant differences regarding application and monitoring of supplementary oxygen, or targeted saturation levels, or for the use of sustained inflations. Comparison of academic and non-academic hospitals showed no significant differences, apart from the targeted saturation levels (SpO₂) at 10 min. of life. Comparison with ILCOR guidelines showed good adherence to the 2005 recommendations.</p> <p>Summary</p> <p>Delivery room management in German, Austrian and Swiss neonatal units was commonly based on written protocols. Only minor differences were found regarding the DR setup, devices used and the targeted ranges for SpO₂and FiO₂. DR management was in good accordance with 2005 ILCOR guidelines, some units already incorporated evidence beyond the ILCOR statement into their routine practice.</p

Delivery room management of very low birth weight infants in Germany, Austria and Switzerland--a comparison of protocols

Surveys from the USA, Australia and Spain have shown significant inter-institutional variation in delivery room (DR) management of very low birth weight infants (VLBWI, <1500g) at birth, despite regularly updated international guidelines