From the RNA-Peptide World: Prebiotic Reaction Conditions Compatible with Lipid Membranes for the Formation of Lipophilic Random Peptides in the Presence of Short Oligonucleotides, and More.

Deciphering the origins of life on a molecular level includes unravelling the numerous interactions that could occur between the most important biomolecules being the lipids, peptides and nucleotides. They were likely all present on the early Earth and all necessary for the emergence of cellular life. In this study, we intended to explore conditions that were at the same time conducive to chemical reactions critical for the origins of life (peptide-oligonucleotide couplings and templated ligation of oligonucleotides) and compatible with the presence of prebiotic lipid vesicles. For that, random peptides were generated from activated amino acids and analysed using NMR and MS, whereas short oligonucleotides were produced through solid-support synthesis, manually deprotected and purified using HPLC. After chemical activation in prebiotic conditions, the resulting mixtures were analysed using LC-MS. Vesicles could be produced through gentle hydration in similar conditions and observed using epifluorescence microscopy. Despite the absence of coupling or ligation, our results help to pave the way for future investigations on the origins of life that may gather all three types of biomolecules rather than studying them separately, as it is still too often the case.

The Origin and Early Evolution of Life: Homochirality Emergence in Prebiotic Environments.

Homochirality is one of the signatures of life. Numerous geological and prebiotic chemistry studies have proved that disordered soups containing small organic molecules, gases, liquids, and minerals (such as those containing phosphorous) yielded racemic mixtures of building blocks for biomolecule assembly. Polymers obtained from these bricks should have been enantiopure with functional properties similar to modern biomolecules or heterochiral with some functions such as catalyzing a chemical transformation unspecifically. Up until now, no clues have been found as to how symmetry breaking occurred. In this review, we highlight the principal achievements regarding the emergence of homochirality during the prebiotic synthesis of building blocks. Furthermore, we tried to focus on approaches based on prebiotic systems chemistry (bottom-up) and laboratory scales to simulate plausible prebiotic messy environments for the emergence of life. We aim with this review to assemble, even partially, the puzzle pieces of the origin of life regarding the relevant phenomenon of homochiral symmetry breaking.

Synthesis of Phospholipids Under Plausible Prebiotic Conditions and Analogies with Phospholipid Biochemistry for Origin of Life Studies.

Phospholipids are essential components of biological membranes and are involved in cell signalization, in several enzymatic reactions, and in energy metabolism. In addition, phospholipids represent an evolutionary and non-negligible step in life emergence. Progress in the past decades has led to a deeper understanding of these unique hydrophobic molecules and their most pertinent functions in cell biology. Today, a growing interest in "prebiotic lipidomics" calls for a new assessment of these relevant biomolecules.

Chemical Analysis of Lipid Boundaries after Consecutive Growth and Division of Supported Giant Vesicles.

The reproduction of the shape of giant vesicles usually results in the increase of their "population" size. This may be achieved on giant vesicles by appropriately supplying "mother" vesicles with membranogenic amphiphiles. The next "generation" of "daughter" vesicles obtained from this "feeding" is inherently difficult to distinguish from the original mothers. Here we report on a method for the consecutive feeding with different fatty acids that each provoke membrane growth and detachment of daughter vesicles from glass microsphere-supported phospholipidic mother vesicles. We discovered that a saturated fatty acid was carried over to the next generation of mothers better than two unsaturated congeners. This has an important bearing on the growth and replication of primitive compartments at the early stages of life. Microsphere-supported vesicles are also a precise analytical tool.

Investigating Prebiotic Protocells for A Comprehensive Understanding of the Origins of Life: A Prebiotic Systems Chemistry Perspective.

Protocells are supramolecular systems commonly used for numerous applications, such as the formation of self-evolvable systems, in systems chemistry and synthetic biology. Certain types of protocells imitate plausible prebiotic compartments, such as giant vesicles, that are formed with the hydration of thin films of amphiphiles. These constructs can be studied to address the emergence of life from a non-living chemical network. They are useful tools since they offer the possibility to understand the mechanisms underlying any living cellular system: Its formation, its metabolism, its replication and its evolution. Protocells allow the investigation of the synergies occurring in a web of chemical compounds. This cooperation can explain the transition between chemical (inanimate) and biological systems (living) due to the discoveries of emerging properties. The aim of this review is to provide an overview of relevant concept in prebiotic protocell research.

Study of HER2/neu status in Qatari women with breast carcinoma.

OBJECTIVE: The study is aimed at determining the prevalence of HER2/neu overexpression in Qatari women with breast cancer and to assess the survival in patients with HER2/neu positive tumors. METHODS: This is a retrospective study of clinical data of 70 Qatari female patients diagnosed with breast cancer during the period 1991 through to 2001, at Hamad Medical Corporation, Doha, Qatar. We also performed a retrospective review of breast tissue sample for those patients using paraffin sections and applying immunohistochemistry staining-[Hercep test (DAKO Inc)] to determine the HER2/neu status. RESULTS: Eighteen patients (26%) were HER2/neu positive (2+ and 3+) with a mean age at diagnosis of 49.3years, and 52 (74%) were negative (0 and 1+) with mean age at diagnosis of 46.6 years. Of the patients with positive HER2/neu, 5 (28%) had a relapse of the disease and 4 (22%) died of the disease during follow up. Of the patients with HER2/neu, negative test 9 (17%) had a relapse of the disease and 10 (19%) died of the disease. The median survival function at mean of covariates for HER2/neu positive patients was 26 months, and for HER2/NEU negative patients was 28 months. CONCLUSION: The prevalence of HER2/neu over expression in Qatari female with breast cancer in this study is 26%, but due to a small sample size it may not reflect really the prevalence. Patient with HER2/neu positive were older at diagnosis than patients with HER2/neu negative, also they had higher relapse rate and mortality. Median survival function was better for HER2/neu negative patients.