Molecular and behavioral changes associated with adult hippocampus-specific SynGAP1 knockout

The synaptic Ras/Rap-GTPase-activating protein (SynGAP1) plays a unique role in regulating specific downstream intracellular events in response to N-methyl-D-aspartate receptor (NMDAR) activation. Constitutive heterozygous loss of SynGAP1 disrupts NMDAR-mediated physiological and behavioral processes, but the disruptions might be of developmental origin. Therefore, the precise role of SynGAP1 in the adult brain, including its relative functional significance within specific brain regions, remains unexplored. The present study constitutes the first attempt in achieving adult hippocampal-specific SynGAP1 knockout using the Cre/loxP approach. Here, we report that this manipulation led to a significant numerical increase in both small and large GluA1 and NR1 immunoreactive clusters, many of which were non-opposed to presynaptic terminals. In parallel, the observed marked decline in the amplitude of spontaneous excitatory currents (sEPSCs) and inter-event intervals supported the impression that SynGAP1 loss might facilitate the accumulation of extrasynaptic glutamatergic receptors. In addition, SynGAP1-mediated signaling appears to be critical for the proper integration and survival of newborn neurons. The manipulation impaired reversal learning in the probe test of the water maze and induced a delay-dependent impairment in spatial recognition memory. It did not significantly affect anxiety or reference memory acquisition but induced a substantial elevation in spontaneous locomotor activity in the open field test. Thus, the present study demonstrates the functional significance of SynGAP1 signaling in the adult brain by capturing several changes that are dependent on NMDAR and hippocampal integrity

A bright, spatially extended lensed galaxy at z = 1.7 behind the cluster RCS2 032727-132623

We present the discovery of an extremely bright and extended lensed source from the second Red Sequence Cluster Survey (RCS2). RCSGA 032727-132609 is spectroscopically confirmed as a giant arc and counter-image of a background galaxy at $z=1.701$, strongly-lensed by the foreground galaxy cluster RCS2 032727-132623 at $z=0.564$. The giant arc extends over $\sim 38$\,\arcsec and has an integrated $g$-band magnitude of 19.15, making it $\sim 20$ times larger and $\sim 4$ times brighter than the prototypical lensed galaxy MS1512-cB58. This is the brightest distant lensed galaxy in the Universe known to date. Its location in the `redshift desert' provides unique opportunities to connect between the large samples of galaxies known at $z\sim3$ and $z\sim1$. We have collected photometry in 9 bands, ranging from $u$ to $K_s$, which densely sample the rest-frame UV and optical light, including the age-sensitive 4000\AA\ break. A lens model is constructed for the system, and results in a robust total magnification of $2.04 \pm 0.16$ for the counter-image; we estimate an average magnification of $17.2 \pm 1.4$ for the giant arc based on the relative physical scales of the arc and counter-image. Fits of single-component spectral energy distribution (SED) models to the photometry result in a moderately young age, $t = 115 \pm 65$\,Myr, small amounts of dust, $E(B-V) \le 0.035$, and an exponentially declining star formation history with \textit{e}-folding time $\tau = 10-100$\,Myr. After correcting for the lensing magnification, we find a stellar mass of $\log(\mathrm{M}/\mathrm{M}_\odot)=10.0 \pm 0.1$. Allowing for episodic star formation, an underlying old burst could contain up to twice the mass inferred from single-component modeling. This stellar mass estimate is consistent with the average stellar mass of a sample of `BM' galaxies ($1.4 < z < 2.0$) studied by Reddy et al. (2006).Comment: 13 pages, 8 figures, abstract abridge

The postweaning social isolation in C57BL/6 mice: preferential vulnerability in the male sex

ISSN:0033-3158ISSN:1432-207

Accuracy of CT Colonography for Detection of Large Adenomas and Cancers

Background Computed tomographic (CT) colonography is a noninvasive option in screening for colorectal cancer. However, its accuracy as a screening tool in asymptomatic adults has not been well defined. Methods We recruited 2600 asymptomatic study participants, 50 years of age or older, at 15 study centers. CT colonographic images were acquired with the use of standard bowel preparation, stool and fluid tagging, mechanical insufflation, and multidetector-row CT scanners (with 16 or more rows). Radiologists trained in CT colonography reported all lesions measuring 5 mm or more in diameter. Optical colonoscopy and histologic review were performed according to established clinical protocols at each center and served as the reference standard. The primary end point was detection by CT colonography of histologically confirmed large adenomas and adenocarcinomas (10 mm in diameter or larger) that had been detected by colonoscopy; detection of smaller colorectal lesions (6 to 9 mm in diameter) was also evaluated. Results Complete data were available for 2531 participants (97%). For large adenomas and cancers, the mean (±SE) per-patient estimates of the sensitivity, specificity, positive and negative predictive values, and area under the receiver-operating-characteristic curve for CT colonography were 0.90±0.03, 0.86±0.02, 0.23±0.02, 0.99± Conclusions In this study of asymptomatic adults, CT colonographic screening identified 90% of subjects with adenomas or cancers measuring 10 mm or more in diameter. These findings augment published data on the role of CT colonography in screening patients with an average risk of colorectal cancer. (ClinicalTrials.gov number, NCT00084929; American College of Radiology Imaging Network [ACRIN] number, 6664.

The Science Case for an Extended Spitzer Mission

Although the final observations of the Spitzer Warm Mission are currently scheduled for March 2019, it can continue operations through the end of the decade with no loss of photometric precision. As we will show, there is a strong science case for extending the current Warm Mission to December 2020. Spitzer has already made major impacts in the fields of exoplanets (including microlensing events), characterizing near Earth objects, enhancing our knowledge of nearby stars and brown dwarfs, understanding the properties and structure of our Milky Way galaxy, and deep wide-field extragalactic surveys to study galaxy birth and evolution. By extending Spitzer through 2020, it can continue to make ground-breaking discoveries in those fields, and provide crucial support to the NASA flagship missions JWST and WFIRST, as well as the upcoming TESS mission, and it will complement ground-based observations by LSST and the new large telescopes of the next decade. This scientific program addresses NASA's Science Mission Directive's objectives in astrophysics, which include discovering how the universe works, exploring how it began and evolved, and searching for life on planets around other stars.Comment: 75 pages. See page 3 for Table of Contents and page 4 for Executive Summar