Zodiacal Exoplanets in Time (ZEIT). VIII. A Two-planet System in Praesepe from K2 Campaign 16

Young planets offer a direct view of the formation and evolution processes that produced the diverse population of mature exoplanet systems known today. The repurposed Kepler mission K2 is providing the first sample of young transiting planets by observing populations of stars in nearby, young clusters and stellar associations. We report the detection and confirmation of two planets transiting K2-264, an M2.5 dwarf in the 650 Myr old Praesepe open cluster. Using our notch-filter search method on the K2 light curve, we identify planets with periods of 5.84 and 19.66 days. This is currently the second known multi-transit system in open clusters younger than 1 Gyr. The inner planet has a radius of 2.27+0.20 -0.16 R⊕ and the outer planet has a radius of 2.27+0.20 -0.18 R ⊕. Both planets are likely mini-Neptunes. These planets are expected to produce radial velocity signals of 3.4 and 2.7 m s-1, respectively, which is smaller than the expected stellar variability in the optical (≃30 m s-1), making mass measurements unlikely in the optical but possible with future near-infrared spectrographs. We use an injection-recovery test to place robust limits on additional planets in the system and find that planets larger than 2 R ⊕ with periods of 1-20 days are unlikely

Usefulness of NGS for diagnosis of dominant beta-thalassemia and unstable hemoglobinopathies in five clinical cases

Unstable hemoglobinopathies (UHs) are rare anemia disorders (RADs) characterized by abnormal hemoglobin (Hb) variants with decreased stability. UHs are therefore easily precipitating, causing hemolysis and, in some cases, leading to dominant beta-thalassemia (dBTHAL). The clinical picture of UHs is highly heterogeneous, inheritance pattern is dominant, instead of recessive as in more prevalent major Hb syndromes, and may occur de novo. Most cases of UHs are not detected by conventional testing, therefore diagnosis requires a high index of suspicion of the treating physician. Here, we highlight the importance of next generation sequencing (NGS) methodologies for the diagnosis of patients with dBTHAL and other less severe UH variants. We present five unrelated clinical cases referred with chronic hemolytic anemia, three of them with severe blood transfusion dependent anemia. Targeted NGS analysis was performed in three cases while whole exome sequencing (WES) analysis was performed in two cases. Five different UH variants were identified correlating with patients' clinical manifestations. Four variants were related to the beta-globin gene (Hb Bristol-Alesha, Hb Debrousse, Hb Zunyi, and the novel Hb Mokum) meanwhile one case was caused by a mutation in the alpha-globin gene leading to Hb Evans. Inclusion of alpha and beta-globin genes in routine NGS approaches for RADs has to be considered to improve diagnosis' efficiency of RAD due to UHs. Reducing misdiagnoses and underdiagnoses of UH variants, especially of the severe forms leading to dBTHAL would also facilitate the early start of intensive or curative treatments for these patients.Genetics of disease, diagnosis and treatmen

Calcium dynamics in catecholamine-containing secretory vesicles

We have used an aequorin chimera targeted to the membrane of the secretory granules to monitor the free [Ca(2+)] inside them in neurosecretory PC12 cells. More than 95% of the probe was located in a compartment with an homogeneous [Ca(2+)] around 40 microM. Cell stimulation with either ATP, caffeine or high-K(+) depolarization increased cytosolic [Ca(2+)] and decreased secretory granule [Ca(2+)] ([Ca(2+)](SG)). Inositol-(1,4,5)-trisphosphate, cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate were all ineffective to release Ca(2+) from the granules. Changes in cytosolic [Na(+)] (0-140 mM) or [Ca(2+)] (0-10 microM) did not modify either ([Ca(2+)](SG)). Instead, [Ca(2+)](SG) was highly sensitive to changes in the pH gradient between the cytosol and the granules. Both carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) and nigericin, as well as cytosolic acidification, reversibly decreased [Ca(2+)](SG), while cytosolic alcalinization reversibly increased [Ca(2+)](SG). These results are consistent with the operation of a H(+)/Ca(2+) antiporter in the vesicular membrane. This antiporter could also mediate the effects of ATP, caffeine and high-K(+) on [Ca(2+)](SG), because all of them induced a transient cytosolic acidification. The FCCP-induced decrease in [Ca(2+)](SG) was reversible in 10-15 min even in the absence of cytosolic Ca(2+) or ATP, suggesting that most of the calcium content of the vesicles is bound to a slowly exchanging Ca(2+) buffer. This large store buffers [Ca(2+)](SG) changes in the long-term but allows highly dynamic free [Ca(2+)](SG) changes to occur in seconds or minutes