Planetary Candidates Observed by Kepler VI: Planet Sample from Q1-Q16 (47 Months)

\We present the sixth catalog of Kepler candidate planets based on nearly 4 years of high precision photometry. This catalog builds on the legacy of previous catalogs released by the Kepler project and includes 1493 new Kepler Objects of Interest (KOIs) of which 554 are planet candidates, and 131 of these candidates have best fit radii <1.5 R_earth. This brings the total number of KOIs and planet candidates to 7305 and 4173 respectively. We suspect that many of these new candidates at the low signal-to-noise limit may be false alarms created by instrumental noise, and discuss our efforts to identify such objects. We re-evaluate all previously published KOIs with orbital periods of >50 days to provide a consistently vetted sample that can be used to improve planet occurrence rate calculations. We discuss the performance of our planet detection algorithms, and the consistency of our vetting products. The full catalog is publicly available at the NASA Exoplanet Archive.Comment: 18 pages, to be published in the Astrophysical Journal Supplement Serie

Importance of Glycosylation on Function of a Potassium Channel in Neuroblastoma Cells

The Kv3.1 glycoprotein, a voltage-gated potassium channel, is expressed throughout the central nervous system. The role of N-glycans attached to the Kv3.1 glycoprotein on conducting and non-conducting functions of the Kv3.1 channel are quite limiting. Glycosylated (wild type), partially glycosylated (N220Q and N229Q), and unglycosylated (N220Q/N229Q) Kv3.1 proteins were expressed and characterized in a cultured neuronal-derived cell model, B35 neuroblastoma cells. Western blots, whole cell current recordings, and wound healing assays were employed to provide evidence that the conducting and non-conducting properties of the Kv3.1 channel were modified by N-glycans of the Kv3.1 glycoprotein. Electrophoretic migration of the various Kv3.1 proteins treated with PNGase F and neuraminidase verified that the glycosylation sites were occupied and that the N-glycans could be sialylated, respectively. The unglycosylated channel favored a different whole cell current pattern than the glycoform. Further the outward ionic currents of the unglycosylated channel had slower activation and deactivation rates than those of the glycosylated Kv3.1 channel. These kinetic parameters of the partially glycosylated Kv3.1 channels were also slowed. B35 cells expressing glycosylated Kv3.1 protein migrated faster than those expressing partially glycosylated and much faster than those expressing the unglycosylated Kv3.1 protein. These results have demonstrated that N-glycans of the Kv3.1 glycoprotein enhance outward ionic current kinetics, and neuronal migration. It is speculated that physiological changes which lead to a reduction in N-glycan attachment to proteins will alter the functions of the Kv3.1 channel

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Importance of glycosylation on function of a potassium channel in neuroblastoma cells

The Kv3.1 glycoprotein, a voltage-gated potassium channel, is expressed throughout the central nervous system. The role of N-glycans attached to the Kv3.1 glycoprotein on conducting and non-conducting functions of the Kv3.1 channel are quite limiting. Glycosylated (wild type), partially glycosylated (N220Q and N229Q), and unglycosylated (N220Q/N229Q) Kv3.1 proteins were expressed and characterized in a cultured neuronal-derived cell model, B35 neuroblastoma cells. Western blots, whole cell current recordings, and wound healing assays were employed to provide evidence that the conducting and non-conducting properties of the Kv3.1 channel were modified by N-glycans of the Kv3.1 glycoprotein. Electrophoretic migration of the various Kv3.1 proteins treated with PNGase F and neuraminidase verified that the glycosylation sites were occupied and that the N-glycans could be sialylated, respectively. The unglycosylated channel favored a different whole cell current pattern than the glycoform. Further the outward ionic currents of the unglycosylated channel had slower activation and deactivation rates than those of the glycosylated Kv3.1 channel. These kinetic parameters of the partially glycosylated Kv3.1 channels were also slowed. B35 cells expressing glycosylated Kv3.1 protein migrated faster than those expressing partially glycosylated and much faster than those expressing the unglycosylated Kv3.1 protein. These results have demonstrated that N-glycans of the Kv3.1 glycoprotein enhance outward ionic current kinetics, and neuronal migration. It is speculated that physiological changes which lead to a reduction in N-glycan attachment to proteins will alter the functions of the Kv3.1 channel

Importance of Glycosylation on Function of a Potassium Channel in Neuroblastoma Cells

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Deactivation rates of ionic currents were slower for aglycoform than glycoform.

<p>A deactivation voltage protocol (A, left panel) was utilized to obtain deactivation currents for B35 cells expressing the glycosylated (A, right panel) and unglycosylated. Scaled deactivation currents from transfected B35 cells expressing either inactivating (B) or non-inactivating (D) current types. Grey lines denote currents at −30 and −50 mV. Traces were scaled to show differences in deactivation kinetics. Deactivation time constant vs. voltage plot of B35 cells expressing glycosylated and unglycosylated Kv3.1 channels for inactivating (C) and non-inactivating (E) currents types.</p

Ionic currents of aglycoform decreased more readily during repetitive depolarization pulses than glycoform.

<p>Currents were elicited by a train of five depolarizing voltage steps to +40 mV once every 525 ms, from a holding potential of −50 mV (A, top panel) for B35 cells expressing glycosylated (A, bottom-left panel) and unglycosylated (A, bottom-right panel) Kv3.1 channels. A bar graph representing the percent of peak current amplitude remaining after the fifth pulse relative to peak current amplitude of initial pulse for the various Kv3.1 channels (B). Asterisks indicate significant differences in mean values at a probability of <i>P</i><0.01 from that of glycosylated Kv3.1.</p

Aglycoform displayed slower activation kinetics of ionic currents than glycoform.

<p>Whole cell currents for glycosylated (A, middle panel; B, top panel) and unglycosylated (A and B, bottom panels) Kv3.1 proteins were elicited from the indicated voltage protocol (A, top panel). Whole cell currents were scaled for inactivating (A) and non-inactivating (B) current types from B35 cells expressing glycosylated and unglycosylated Kv3.1 proteins. Right panels show traces at expanded time scales and grey lines denote currents at +40 and +60 mV. Traces were scaled to show differences in activation kinetics. Conductance-voltage (g/gmax) curves of both inactivating (C) and non-inactivating (D) current types for glycosylated and unglycosylated Kv3.1 channels. Rise times of inactivating (E) and non-inactivating (F) currents types. <i>n</i> represents number of cells.</p

Characterization of Kv3.1 proteins expressed in B35 cells.

<p>Western blots of wild type (Wt), N220Q, N229Q, and N220Q/N229Q Kv3.1 proteins. Kv3.1 proteins were detected when heterologously expressed in B35 cells (A). Arrows and lines denote the type of <i>N</i>-glycan attached to the Kv3.1 protein. Assignments of the various glycosylated and unglycosylated Kv3.1 proteins were based on immunoband shifts produced by glycosidase treatment. N220Q and N229Q proteins were digested (+) and undigested (−) with neuraminidase (B), PNGase F (C) and Endo H (D). A solid line on image indicates that samples were run on a different blot (B). The numbers adjacent to the Western blots represent the Kaleidoscope markers (in KDa). Similar migration patterns were observed on at least three separate Western blots.</p