ALBERT

Description: 〈p〉The hypothalamus controls essential social behaviors and homeostatic functions. However, the cellular architecture of hypothalamic nuclei—including the molecular identity, spatial organization, and function of distinct cell types—is poorly understood. Here, we developed an imaging-based in situ cell-type identification and mapping method and combined it with single-cell RNA-sequencing to create a molecularly annotated and spatially resolved cell atlas of the mouse hypothalamic preoptic region. We profiled ~1 million cells, identified ~70 neuronal populations characterized by distinct neuromodulatory signatures and spatial organizations, and defined specific neuronal populations activated during social behaviors in male and female mice, providing a high-resolution framework for mechanistic investigation of behavior circuits. The approach described opens a new avenue for the construction of cell atlases in diverse tissues and organisms.〈/p〉

Description: INTRODUCTION The recent great earthquakes of 26 December 2004 (Sumatra, Indonesia, Mw 9.2), 26 February 2010 (Maule, Chile, Mw 8.8), and 11 March 2011 (Tohoku-oki, Japan, Mw 9.0) have once again brought to the forefront the urgent need for early tsunami warning. These warnings mostly rely on magnitude and location of an earthquake. A large/great magnitude subduction-zone earthquake with rupture area extending up to the trench is potentially a tsunamigenic event. The appropriate magnitudes for tsunami warning are those that are based on long-period seismic waves (Abe 1979), e.g., the moment magnitude, Mw (Kanamori 1977). Recently, W-phase (the long-period wave that arrives between P and S waves) has been used to compute Mw (Kanamori and Rivera 2008; Hayes et al. 2009). This magnitude can be determined in a relatively short time. For example, the first moment tensor solutions of the Tohoku-oki earthquake, based on inversion of W-phase at teleseismic distances, became available in 20 min (Duputel et al. 2011). For this reason, Mw computed from W-phase is especially useful for tsunami alerts at distant sites. It is at local distances that early tsunami warning becomes difficult. Even then, Mw based on inversion of W-phase recorded at regional distances may be useful. Tests show that Mw of Mexican subduction thrust earthquakes, based on W-phase recorded on broadband, regional seismograms, can be estimated in ∼7 min after the occurrence of the event (Pérez-Campos et al. 2010). In recent years there has been an increase in GPS stations along the coastal region of some subduction zones. Some of these stations are operated in continuous mode (either in real-time high-rate mode or periodic low-rate download mode), and others in campaign mode. Static displacement vectors obtained from GPS data...

Description: Ca2+-activated Cl− channels (CaCCs) are exceptionally well adapted to subserve diverse physiological roles, from epithelial fluid transport to sensory transduction, because their gating is cooperatively controlled by the interplay between ionotropic and metabotropic signals. A molecular understanding of the dual regulation of CaCCs by voltage and Ca2+ has recently become possible with the discovery that Ano1 (TMEM16a) is an essential subunit of CaCCs. Ano1 can be gated by Ca2+ or by voltage in the absence of Ca2+, but Ca2+- and voltage-dependent gating are very closely coupled. Here we identify a region in the first intracellular loop that is crucial for both Ca2+ and voltage sensing. Deleting 448EAVK in the first intracellular loop dramatically decreases apparent Ca2+ affinity. In contrast, mutating the adjacent amino acids 444EEEE abolishes intrinsic voltage dependence without altering the apparent Ca2+affinity. Voltage-dependent gating of Ano1 measured in the presence of intracellular Ca2+ was facilitated by anions with high permeability or by an increase in [Cl−]e. Our data show that the transition between closed and open states is governed by Ca2+ in a voltage-dependent manner and suggest that anions allosterically modulate Ca2+-binding affinity. This mechanism provides a unified explanation of CaCC channel gating by voltage and ligand that has long been enigmatic.

Description: To identify genes that affect body mass index (BMI) in American Indians who are predominately of Pima Indian heritage, we previously completed a genome-wide association study in 1120 American Indians. That study also included follow-up genotyping for 9 SNPs in 2133 additional subjects. A comprehensive follow-up study has subsequently been completed where 292 SNPs were genotyped in 3562 subjects, of which 128 SNPs were assessed for replication in 3238 additional subjects. In the combined subjects ( n = 6800), BMI associations for two SNPs, rs12882548 and rs11652094, approached genome-wide significance ( P = 6.7 x 10 –7 and 8.1 x 10 –7 , respectively). Rs12882548 is located in a gene desert on chromosome 14 and rs11652094 maps near MAP2K3 . Several SNPs in the MAP2K3 region including rs11652094 were also associated with BMI in Caucasians from the GIANT consortium ( P = 10 –2 –10 –5 ), and the combined P -values across both American Indians and Caucasian were P = 10 –4 –10 –9 . Follow-up sequencing across MAP2K3 identified several paralogous sequence variants indicating that the region may have been duplicated. MAP2K3 expression levels in adipose tissue biopsies were positively correlated with BMI, although it is unclear if this correlation is a cause or effect. In vitro studies with cloned MAP2K3 promoters suggest that MAP2K3 expression may be up-regulated during adipogenesis. Microarray analyses of mouse hypothalamus cells expressing constitutively active MAP2K3 identified several up-regulated genes involved in immune/inflammatory pathways and a gene, Hap1 , thought to play a role in appetite regulation. We conclude that MAP2K3 is a reproducible obesity locus that may affect body weight via complex mechanisms involving appetite regulation and hypothalamic inflammation.

Description: Sedimentologic, provenance, geochronologic, and magnetostratigraphic results from clastic nonmarine deposits in the northern Altiplano Plateau of southern Peru (14–15°S) demonstrate late Eocene–Oligocene (37–26 Ma) accumulation of the 〉4-km-thick San Jerónimo (Puno) Group within a retroarc foreland basin related to early Andean shortening and crustal thickening. Punctuated Oligocene (29–26 Ma) displacement along deep-seated contractional structures, as revealed by growth stratal relationships, abruptly partitioned this regional flexural basin and established the structural boundaries of the smaller intermontane Ayaviri Basin, which continued to evolve in a hinterland setting during late Oligocene–Miocene shortening. This brief episode of shortening along the Altiplano–Eastern Cordillera boundary is correlated with exceptionally rapid sediment accumulation (〉1100–1800 m/m.y.), tightly constrained to 30–28 Ma on the basis of U-Pb geochronology and magnetic polarity stratigraphy. Provenance data from detrital zircon U-Pb age populations and sandstone compositions indicate derivation from a complex belt of Paleogene shortening and probable basin inversion in the Western Cordillera that was subsequently overprinted by Andean arc magmatism. This early Andean zone is interpreted as the along-strike continuation of the better-exposed Marañon fold-thrust belt to the north (5–13°S) and a proposed belt of shortening to the south along the Chilean Precordillera and Western Cordillera of Bolivia and northern Argentina (17–25°S). Subsequent focusing of late Oligocene shortening along the Eastern Cordillera–Altiplano boundary may have been linked to shallowing of the subducting slab and potential reactivation of crustal anisotropies.

Description: We have investigated the X-ray spectral properties of a sample of 138 X-ray sources detected serendipitously in XMM–Newton observations of the Galactic plane, at an intermediate to faint flux level. We divide our sample into five subgroups according to the spectral hardness of the sources, and stack (i.e. co-add) the individual source spectra within each subgroup. As expected these stacked spectra show a softening trend from the hardest to the softest subgroups, which is reflected in the inferred line-of-sight column density. The spectra of the three hardest subgroups are characterized by a hard continuum plus superimposed Fe-line emission in the 6–7 keV bandpass. The average equivalent width (EW) of the 6.7-keV He-like Fe Kα line is 170 $^{+35}_{-32}$ eV, whereas the 6.4-keV Fe K fluorescence line from neutral iron and the 6.9-keV H-like Fe Lyα line have EWs of 89 $^{+26}_{-25}$ and 81 $^{+30}_{-29}$ eV, respectively, i.e. roughly half that of the 6.7-keV line. The remaining subgroups exhibit soft thermal spectra. Virtually all of the spectrally soft X-ray sources can be associated with relatively nearby coronally active late-type stars, which are evident as bright near-infrared (NIR) objects within the X-ray error circles. On a similar basis only a minority of the spectrally hard X-ray sources have likely NIR identifications. The average continuum and Fe-line properties of the spectrally hard sources are consistent with those of magnetic cataclysmic variables but the direct identification of large numbers of such systems in Galactic X-ray surveys, probing intermediate to faint flux levels, remains challenging.

Description: The Galactic Centre hosts a puzzling stellar population in its inner few parsecs, with a high abundance of surprisingly young, relatively massive stars bound within the deep potential well of the central supermassive black hole, Sagittarius A* (ref. 1). Previous studies suggest that the population of objects emitting soft X-rays (less than 10 kiloelectronvolts) within the surrounding hundreds of parsecs, as well as the population responsible for unresolved X-ray emission extending along the Galactic plane, is dominated by accreting white dwarf systems. Observations of diffuse hard-X-ray (more than 10 kiloelectronvolts) emission in the inner 10 parsecs, however, have been hampered by the limited spatial resolution of previous instruments. Here we report the presence of a distinct hard-X-ray component within the central 4 x 8 parsecs, as revealed by subarcminute-resolution images in the 20-40 kiloelectronvolt range. This emission is more sharply peaked towards the Galactic Centre than is the surface brightness of the soft-X-ray population. This could indicate a significantly more massive population of accreting white dwarfs, large populations of low-mass X-ray binaries or millisecond pulsars, or particle outflows interacting with the surrounding radiation field, dense molecular material or magnetic fields. However, all these interpretations pose significant challenges to our understanding of stellar evolution, binary formation, and cosmic-ray production in the Galactic Centre.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perez, Kerstin -- Hailey, Charles J -- Bauer, Franz E -- Krivonos, Roman A -- Mori, Kaya -- Baganoff, Frederick K -- Barriere, Nicolas M -- Boggs, Steven E -- Christensen, Finn E -- Craig, William W -- Grefenstette, Brian W -- Grindlay, Jonathan E -- Harrison, Fiona A -- Hong, Jaesub -- Madsen, Kristin K -- Nynka, Melania -- Stern, Daniel -- Tomsick, John A -- Wik, Daniel R -- Zhang, Shuo -- Zhang, William W -- Zoglauer, Andreas -- England -- Nature. 2015 Apr 30;520(7549):646-9. doi: 10.1038/nature14353.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Columbia Astrophysics Laboratory, Columbia University, 550 West 120th Street, Room 1027, New York, New York 10027, USA [2] Haverford College, 370 Lancaster Avenue, KINSC L109, Haverford, Pennsylvania 19041, USA. ; Columbia Astrophysics Laboratory, Columbia University, 550 West 120th Street, Room 1027, New York, New York 10027, USA. ; 1] Instituto de Astrofisica, Facultad de Fisica, Pontificia Universidad Catolica de Chile, 306, Santiago 22, Chile [2] Millennium Institute of Astrophysics, Vicuna Mackenna 4860, 7820436 Macul, Santiago, Chile [3] Space Science Institute, 4750 Walnut Street, Suite 205, Boulder, Colorado 80301, USA. ; Space Science Laboratory, UC Berkeley, 7 Gauss Way, Berkeley, California 94720, USA. ; Kavli Institute for Astrophysics and Space Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 37-555, Cambridge, Massachusetts 02139, USA. ; DTU Space, National Space Institute, Technical University of Denmark, Elektrovej 327, DK-2800 Lyngby, Denmark. ; 1] Space Science Laboratory, UC Berkeley, 7 Gauss Way, Berkeley, California 94720, USA [2] Lawrence Livermore National Laboratory, PO Box 808, Livermore, California 94551-0808, USA. ; Cahill Center for Astronomy and Astrophysics, 1200 East California Boulevard, MC 290-17, California Institute of Technology, Pasadena, California 91125, USA. ; Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, MS-83, Cambridge, Massachusetts 02138, USA. ; Jet Propulsion Laboratory, California Institute of Technology, Pasadena, 4800 Oak Grove Drive, MS 169-221, California 91109, USA. ; NASA Goddard Space Flight Center, 8800 Greenbelt Road, Code 662, Greenbelt, Maryland 20771, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25925477" target="_blank"〉PubMed〈/a〉

Description: 〈p〉The hypothalamus controls essential social behaviors and homeostatic functions. However, the cellular architecture of hypothalamic nuclei, including the molecular identity, spatial organization, and function of distinct cell types, is poorly understood. Here, we developed an imaging-based in situ cell type identification and mapping method and combined it with single-cell RNA-sequencing to create a molecularly annotated and spatially resolved cell atlas of the mouse hypothalamic preoptic region. We profiled ~1 million cells, identified ~70 neuronal populations characterized by distinct neuromodulatory signatures and spatial organizations, and defined specific neuronal populations activated during social behaviors in male and female mice, providing a high-resolution framework for mechanistic investigation of behavior circuits. The approach described opens a new avenue for the construction of cell atlases in diverse tissues and organisms.〈/p〉