Cancer Genome Sequencing and Its Implications for Personalized Cancer Vaccines

New DNA sequencing platforms have revolutionized human genome sequencing. The dramatic advances in genome sequencing technologies predict that the $1,000 genome will become a reality within the next few years. Applied to cancer, the availability of cancer genome sequences permits real-time decision-making with the potential to affect diagnosis, prognosis, and treatment, and has opened the door towards personalized medicine. A promising strategy is the identification of mutated tumor antigens, and the design of personalized cancer vaccines. Supporting this notion are preliminary analyses of the epitope landscape in breast cancer suggesting that individual tumors express significant numbers of novel antigens to the immune system that can be specifically targeted through cancer vaccines

Race in health research : considerations for researchers and research ethics committees

This article provides ethical guidance on using race in health research as a variable or in defining the study population. To this end, a plain, non-exhaustive checklist is provided for researchers and research ethics committees, preceded by a brief introduction on the need for justification when using race as a variable or in defining a study population, the problem of exoticism, that distinctions pertain between race, ethnicity and ancestry, the problematic naming of races, and that race does not serve well as a presumed biological construct in genetic research.http://www.sajbl.org.zaam2024PsychiatryNon

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Predicting the Highest Intensity Ion in Multiple Charging Envelopes Observed for Denatured Proteins during Electrospray Ionization Mass Spectrometry by Inspection of the Amino Acid Sequence

A simple, manual method for predicting the highest intensity charge states (HICS) of denatured protein ions generated by electrospray ionization based on inspection of the proteins’ amino acid sequence is proposed. The HICS is accurately predicted by identifying groupings of nearby basic amino acids in the positive mode or acidic amino acid residues in the negative mode. The method assumes that the likelihood of having more than one charge per group becomes less likely due to Coulombic repulsion of like charges. It is shown empirically that a spacing of at least three noncharged residues is required between charged amino acids for the charge state with the highest intensity. Verification of this method is presented, and its limitations are identified. It is fast, inexpensive, and provides similar, although less detailed, information as state-of-the-art methods that rely on computational calculations. With a few exceptions, the highest intensity charge states were predicted to an average of one charge state of the experimental data. For those proteins whose HICS were not accurately estimated, the experimental values fell short of the predictions. Upon reduction of the disulfide bonds of these proteins, the experimental HICS became closer to the predicted values, suggesting that charging lower than the prediction can be attributed to conformational inflexibility of those proteins

Effects of Amino Acid Additives on Protein Stability during Electrothermal Supercharging in ESI-MS

The surprising formation of highly charged protein ions from aqueous ammonium bicarbonate solution is a fascinating phenomenon referred to as electrothermal supercharging (ETS). Although the precise mechanism involved is not clearly understood, previous studies predominantly suggest that ETS is due to native protein destabilization in the presence of bicarbonate anion inside the electrospray ionization droplets under high temperatures and spray voltages. To evaluate existing hypotheses surrounding the underlying mechanism of ETS, the effects of several additives on protein charging under ETS conditions were investigated. The changes in the protein charge state distributions were compared by measuring the ratios between the intensities of highest intensity charge states of native and unfolded protein envelopes and shifts in the lowest and highest observed charge states. This study demonstrated that source temperature plays a more important role in ETS compared to spray voltage, especially when using a nebulized microelectrospray ionization source. Moreover, the effect of amino acids on ETS were generally in good agreement with the extensive literature available on the stabilization or destabilization of proteins by these additives in bulk solution. Among the natural amino acids, protein supercharging was significantly reduced by proline and glycine; however, imidazole provided the highest degree of noncovalent complex stabilization against ETS, outperforming the amino acids. Overall, our study shows that the simple addition of stabilizing reagents such as proline and imidazole can reduce the extent of apparent protein unfolding and supercharging in ammonium bicarbonate solution and provide evidence against the roles of charge depletion and thermal unfolding during ETS