Regulated expression of mature human insulin in the liver of transgenic mice

AbstractTransgenic mice expressing either human proinsulin cDNA or mutated proinsulin cDNA in the liver were created. The human proinsulin cDNA was mutated to generate a protein cleavable by the ubiquitous prohormone convertase furin, thus leading to mature insulin peptide. All transgenic lines expressed human C-peptide in the blood, whose level varied according to nutritional conditions. High performance liquid chromatography fractionation of mouse serum revealed that mutant proinsulin was effectively processed into mature insulin in vivo. This transgenic mouse model provides a useful tool for further prospects of gene therapy of insulin-dependent diabetes mellitus

The SOPHIE search for northern extrasolar planets XIV. A temperate (Teq ~ 300 K) super-earth around the nearby star Gliese 411

Periodic radial velocity variations in the nearby M-dwarf star Gl 411 are reported, based on measurements with the SOPHIE spectrograph. Current data do not allow us to distinguish between a 12.95-day period and its one-day alias at 1.08 days, but favour the former slightly. The velocity variation has an amplitude of 1.6 m s−1, making this the lowest-amplitude signal detected with SOPHIE up to now. We have performed a detailed analysis of the significance of the signal and its origin, including extensive simulations with both uncorrelated and correlated noise, representing the signal induced by stellar activity. The signal is significantly detected, and the results from all tests point to its planetary origin. Additionally, the presence of an additional acceleration in the velocity time series is suggested by the current data. On the other hand, a previously reported signal with a period of 9.9 days, detected in HIRES velocities of this star, is not recovered in the SOPHIE data. An independent analysis of the HIRES dataset also fails to unveil the 9.9-day signal. If the 12.95-day period is the real one, the amplitude of the signal detected with SOPHIE implies the presence of a planet, called Gl 411 b, with a minimum mass of around three Earth masses, orbiting its star at a distance of 0.079 AU. The planet receives about 3.5 times the insolation received by Earth, which implies an equilibrium temperature between 256 and 350 K, and makes it too hot to be in the habitable zone. At a distance of only 2.5 pc, Gl 411 b, is the third closest low-mass planet detected to date. Its proximity to Earth will permit probing its atmosphere with a combination of high-contrast imaging and high-dispersion spectroscopy in the next decade

A pair of TESS planets spanning the radius valley around the nearby mid-M dwarf LTT 3780

We present the confirmation of two new planets transiting the nearby mid-M dwarf LTT 3780 (TIC 36724087, TOI-732, $V=13.07$, $K_s=8.204$, $R_s$=0.374 R$_{\odot}$, $M_s$=0.401 M$_{\odot}$, d=22 pc). The two planet candidates are identified in a single TESS sector and are validated with reconnaissance spectroscopy, ground-based photometric follow-up, and high-resolution imaging. With measured orbital periods of $P_b=0.77$ days, $P_c=12.25$ days and sizes $r_{p,b}=1.33\pm 0.07$ R$_{\oplus}$, $r_{p,c}=2.30\pm 0.16$ R$_{\oplus}$, the two planets span the radius valley in period-radius space around low mass stars thus making the system a laboratory to test competing theories of the emergence of the radius valley in that stellar mass regime. By combining 63 precise radial-velocity measurements from HARPS and HARPS-N, we measure planet masses of $m_{p,b}=2.62^{+0.48}_{-0.46}$ M$_{\oplus}$ and $m_{p,c}=8.6^{+1.6}_{-1.3}$ M$_{\oplus}$, which indicates that LTT 3780b has a bulk composition consistent with being Earth-like, while LTT 3780c likely hosts an extended H/He envelope. We show that the recovered planetary masses are consistent with predictions from both photoevaporation and from core-powered mass loss models. The brightness and small size of LTT 3780, along with the measured planetary parameters, render LTT 3780b and c as accessible targets for atmospheric characterization of planets within the same planetary system and spanning the radius valley.Comment: Accepted to AJ. 8 figures, 6 tables. CSV file of the RV measurements (i.e. Table 2) are included in the source cod

Limb proportions show developmental plasticity in response to embryo movement

Animals have evolved limb proportions adapted to different environments, but it is not yet clear to what extent these proportions are directly influenced by the environment during prenatal development. The developing skeleton experiences mechanical loading resulting from embryo movement. We tested the hypothesis that environmentally-induced changes in prenatal movement influence embryonic limb growth to alter proportions. We show that incubation temperature influences motility and limb bone growth in West African Dwarf crocodiles, producing altered limb proportions which may, influence post-hatching performance. Pharmacological immobilisation of embryonic chickens revealed that altered motility, independent of temperature, may underpin this growth regulation. Use of the chick also allowed us to merge histological, immunochemical and cell proliferation labelling studies to evaluate changes in growth plate organisation, and unbiased array profiling to identify specific cellular and transcriptional targets of embryo movement. This disclosed that movement alters limb proportions and regulates chondrocyte proliferation in only specific growth plates. This selective targeting is related to intrinsic mTOR (mechanistic target of rapamycin) pathway activity in individual growth plates. Our findings provide new insights into how environmental factors can be integrated to influence cellular activity in growing bones and ultimately gross limb morphology, to generate phenotypic variation during prenatal development

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Neuropsychosocial profiles of current and future adolescent alcohol misusers

A comprehensive account of the causes of alcohol misuse must accommodate individual differences in biology, psychology and environment, and must disentangle cause and effect. Animal models1 can demonstrate the effects of neurotoxic substances; however, they provide limited insight into the psycho-social and higher cognitive factors involved in the initiation of substance use and progression to misuse. One can search for pre-existing risk factors by testing for endophenotypic biomarkers2 in non-using relatives; however, these relatives may have personality or neural resilience factors that protect them from developing dependence3. A longitudinal study has potential to identify predictors of adolescent substance misuse, particularly if it can incorporate a wide range of potential causal factors, both proximal and distal, and their influence on numerous social, psychological and biological mechanisms4. Here we apply machine learning to a wide range of data from a large sample of adolescents (n = 692) to generate models of current and future adolescent alcohol misuse that incorporate brain structure and function, individual personality and cognitive differences, environmental factors (including gestational cigarette and alcohol exposure), life experiences, and candidate genes. These models were accurate and generalized to novel data, and point to life experiences, neurobiological differences and personality as important antecedents of binge drinking. By identifying the vulnerability factors underlying individual differences in alcohol misuse, these models shed light on the aetiology of alcohol misuse and suggest targets for prevention

Les temps de la mémoire : de quelques usages stratégiques des imaginaires

Mémoire et identité sont inextricablement liées: tant les individus que les collectivités se constituent par une mémoire, construction de sens qui signifie en regard du présent. Dans quelles conditions s'exerce en ce sens le pouvoir des imaginaires héroïques? Le présent ouvrage propose aux chercheurs un travail de cadrage terminologique et conceptuel, ainsi que l'indispensable mise en place des concepts interdisciplinaires qui permettent de s'interroger sur le rôle des représentations dans la constitution des identités

Avoidance towards humans in two genetic populations of pheasants

International audienc

Line-by-line Velocity Measurements: an Outlier-resistant Method for Precision Velocimetry

International audienceAbstract We present a new algorithm for precision radial velocity (pRV) measurements, a line-by-line (LBL) approach designed to handle outlying spectral information in a simple but efficient manner. The effectiveness of the LBL method is demonstrated on two data sets, one obtained with SPIRou on Barnard’s star, and the other with the High Accuracy Radial velocity Planet Searcher (HARPS) on Proxima Centauri. In the near-infrared, the LBL provides a framework for meters-per-second-level accuracy in pRV measurements despite the challenges associated with telluric absorption and sky emission lines. We confirm with SPIRou measurements spanning 2.7 yr that the candidate super-Earth on a 233 day orbit around Barnard’s star is an artifact due to a combination of time sampling and activity. The LBL analysis of the Proxima Centauri HARPS post-upgrade data alone easily recovers the Proxima b signal and also provides a 2 σ detection of the recently confirmed 5 day Proxima d planet, but argues against the presence of the candidate Proxima c with a period of 1900 days. We provide evidence that the Proxima c signal is associated with small, unaccounted systematic effects affecting the HARPS-TERRA template-matching radial velocity extraction method for long-period signals. Finally, the LBL framework provides a very effective activity indicator, akin to the FWHM derived from the cross-correlation function, from which we infer a rotation period of 92.1 − 3.5 + 4.2 days for Proxima