Stability-mediated epistasis constrains the evolution of an influenza protein.

John Maynard Smith compared protein evolution to the game where one word is converted into another a single letter at a time, with the constraint that all intermediates are words: WORD→WORE→GORE→GONE→GENE. In this analogy, epistasis constrains evolution, with some mutations tolerated only after the occurrence of others. To test whether epistasis similarly constrains actual protein evolution, we created all intermediates along a 39-mutation evolutionary trajectory of influenza nucleoprotein, and also introduced each mutation individually into the parent. Several mutations were deleterious to the parent despite becoming fixed during evolution without negative impact. These mutations were destabilizing, and were preceded or accompanied by stabilizing mutations that alleviated their adverse effects. The constrained mutations occurred at sites enriched in T-cell epitopes, suggesting they promote viral immune escape. Our results paint a coherent portrait of epistasis during nucleoprotein evolution, with stabilizing mutations permitting otherwise inaccessible destabilizing mutations which are sometimes of adaptive value. DOI:http://dx.doi.org/10.7554/eLife.00631.001

The impact of health on professionally active people's incomes in Poland. Microeconometric analysis

The outcome of the research confirms the occurrence of positive interaction between professionally active people's incomes and the self-assessed state of health. People declaring a bad state of health have incomes by 20% on average lower than people who enjoy good health (assuming that the remaining characteristics of the surveyed person are the same). In case of men, the impact of health state on incomes is slightly greater than in case of women.Wyniki badań potwierdzają istnienie pozytywnej zależności dochodów osób aktywnych zawodowo od stanu zdrowia mierzonego jego samooceną. Osoby deklarujące zły stan zdrowia osiągają dochody przeciętnie o 20% niższe niż osoby, które cieszą się dobrym stanem zdrowia (przy założeniu, że pozostałe charakterystyki badanej osoby są takie same). W przypadku mężczyzn zależność dochodów od stanu zdrowia jest nieznacznie silniejsza niż w przypadku kobiet

The Discovery of Vibrationally-Excited H_2 in the Molecular Cloud near GRB 080607

GRB 080607 has provided the first strong observational signatures of molecular absorption bands toward any galaxy hosting a gamma-ray burst. Despite the identification of dozens of features as belonging to various atomic and molecular (H_2 and CO) carriers, many more absorption features remained unidentified. Here we report on a search among these features for absorption from vibrationally-excited H_2, a species that was predicted to be produced by the UV flash of a GRB impinging on a molecular cloud. Following a detailed comparison between our spectroscopy and static, as well as dynamic, models of H_2* absorption, we conclude that a column density of 10^{17.5+-0.2} cm^{-2} of H_2* was produced along the line of sight toward GRB 080607. Depending on the assumed amount of dust extinction between the molecular cloud and the GRB, the model distance between the two is found to be in the range 230--940 pc. Such a range is consistent with a conservative lower limit of 100 pc estimated from the presence of Mg I in the same data. These distances show that substantial molecular material is found within hundreds of pc from GRB 080607, part of the distribution of clouds within the GRB host galaxy.Comment: Submitted to ApJL, 6 pages emulate

The Rapidly Fading Afterglow from the Gamma-Ray Burst of 1999 May 6

We report on the discovery of the radio afterglow from the gamma-ray burst (GRB) of 1999 May 6 (GRB 990506) using the Very Large Array (VLA). The radio afterglow was detected at early times (1.5 days), but began to fade rapidly sometime between 1 and 5 days after the burst. If we attribute the radio emission to the forward shock from an expanding fireball, then this rapid onset of the decay in the radio predicts that the corresponding optical transient began to decay between 1 and 5 minutes after the burst. This could explain why no optical transient for GRB 990506 was detected in spite of numerous searches. The cause of the unusually rapid onset of the decay for the afterglow is probably the result of an isotropically energetic fireball expanding into a low density circumburst environment. At the location of the radio afterglow we find a faint (R ~ 24 mag) host galaxy with a double morphology.Comment: in press at ApJ Letters, 13 page LaTeX document includes 2 postscript figure

Neutral genetic drift can aid functional protein evolution

BACKGROUND: Many of the mutations accumulated by naturally evolving proteins are neutral in the sense that they do not significantly alter a protein's ability to perform its primary biological function. However, new protein functions evolve when selection begins to favor other, "promiscuous" functions that are incidental to a protein's biological role. If mutations that are neutral with respect to a protein's primary biological function cause substantial changes in promiscuous functions, these mutations could enable future functional evolution. RESULTS: Here we investigate this possibility experimentally by examining how cytochrome P450 enzymes that have evolved neutrally with respect to activity on a single substrate have changed in their abilities to catalyze reactions on five other substrates. We find that the enzymes have sometimes changed as much as four-fold in the promiscuous activities. The changes in promiscuous activities tend to increase with the number of mutations, and can be largely rationalized in terms of the chemical structures of the substrates. The activities on chemically similar substrates tend to change in a coordinated fashion, potentially providing a route for systematically predicting the change in one function based on the measurement of several others. CONCLUSIONS: Our work suggests that initially neutral genetic drift can lead to substantial changes in protein functions that are not currently under selection, in effect poising the proteins to more readily undergo functional evolution should selection "ask new questions" in the future

The Afterglow, Energetics and Host Galaxy of the Short-Hard Gamma-Ray Burst 051221a

We present detailed optical, X-ray and radio observations of the bright afterglow of the short gamma-ray burst 051221a obtained with Gemini, Swift/XRT, and the Very Large Array, as well as optical spectra from which we measure the redshift of the burst, z=0.5464. At this redshift the isotropic-equivalent prompt energy release was about 1.5 x 10^51 erg, and using the standard afterglow synchrotron model we find that the blastwave kinetic energy is similar, E_K,iso ~ 8.4 x 10^51 erg. An observed jet break at t ~ 5 days indicates that the opening angle is ~ 7 degrees and the total beaming-corrected energy is therefore ~ 2.5 x 10^49 erg, comparable to the values inferred for previous short GRBs. We further show that the burst experienced an episode of energy injection by a factor of 3.4 between t=1.4 and 3.4 hours, which was accompanied by reverse shock emission in the radio band. This result provides continued evidence that the central engines of short GRBs may be active significantly longer than the duration of the burst and/or produce a wide range of Lorentz factors. Finally, we show that the host galaxy of GRB051221a is actively forming stars at a rate of about 1.6 M_solar/yr, but at the same time exhibits evidence for an appreciable population of old stars (~ 1 Gyr) and near solar metallicity. The lack of bright supernova emission and the low circumburst density (n ~ 10^-3 cm^-3) continue to support the idea that short bursts are not related to the death of massive stars and are instead consistent with a compact object merger. Given that the total energy release is a factor of ~ 10 larger than the predicted yield for a neutrino annihilation mechanism, this suggests that magnetohydrodynamic processes may be required to power the burst.Comment: Final version (to appear in ApJ on 20 September 2006

Investigating the KNDy hypothesis in humans by co-administration of kisspeptin, neurokinin B and naltrexone in men

Context: A subpopulation of hypothalamic neurons co-localise three neuropeptides namely kisspeptin, neurokinin B (NKB) and dynorphin collectively termed KNDy neurons. Animal studies suggest they interact to affect pulsatile GnRH release (KNDy hypothesis); kisspeptin stimulates, NKB modulates and dynorphin (an opioid) inhibits. Objective: To investigate the KNDy hypothesis in humans, we assessed for the first time the effects of co-administration of kisspeptin-54, NKB and an opioid receptor antagonist, naltrexone on LH pulsatility (surrogate marker for GnRH pulsatility) and gonadotropin release. Design, setting and participants: Ethically approved prospective, single-blinded placebo-controlled study. Healthy male volunteers (n=5/group) attended our research facility for 8 study visits. Intervention and main outcome measure: After 1h baseline blood sampling, participants received a different intervention at each visit: oral 50mg naltrexone (NAL), 8h intravenous infusions of vehicle, 2.56nmol/kg/h NKB (NKB), 0.1nmol/kg/h kissspeptin-54 (KP) alone and in combination. Frequent blood sampling to measure plasma gonadotropins and sex steroids was conducted and LH pulsatility was determined using blinded deconvolution analysis. Results: All kisspeptin and naltrexone containing groups potently increased LH and LH pulsatility (p<0.001 vs vehicle). NKB alone did not affect gonadotropins. NKB+KP had significantly lower increases in gonadotropins compared with kisspeptin alone (p<0.01). NAL+KP was the only group to significantly increase LH pulse amplitude (p<0.001 vs vehicle). Conclusions: Our results suggest significant interactions between the KNDy neuropeptides on LH pulsatility and gonadotropin release in humans. This has important implications for improving our understanding of GnRH pulse generation in humans