Sodium and Calcium Current-Mediated Pacemaker Neurons and Respiratory Rhythm Generation

The breathing motor pattern in mammals originates in brainstem networks. Whether pacemaker neurons play an obligatory role remains a key unanswered question. We performed whole-cell recordings in the pre-Botzinger complex in slice preparations from neonatal rodents and tested for pacemaker activity. We observed persistent Na+ current (INaP)-mediated bursting in ∼5% of inspiratory neurons in postnatal day 0 (P0)-P5 and in P8-P10 slices. INaP-mediated bursting was voltage dependent and blocked by 20 μm riluzole (RIL). We found Ca2+ current (ICa)-dependent bursting in 7.5% of inspiratory neurons in P8-P10 slices, but in P0-P5 slices these cells were exceedingly rare (0.6%). This bursting was voltage independent and blocked by 100 μm Cd2+ or flufenamic acid (FFA) (10-200 μm), which suggests that a Ca2+-activated inward cationic current (ICAN) underlies burst generation. These data substantiate our observation that P0-P5 slices exposed to RIL contain few (if any) pacemaker neurons, yet maintain respiratory rhythm. We also show that 20 nm TTX or coapplication of 20 μm RIL + FFA (100-200 μm) stops the respiratory rhythm, but that adding 2 μm substance P restarts it. We conclude that INaP and ICAN enhance neuronal excitability and promote rhythmogenesis, even if their magnitude is insufficient to support bursting-pacemaker activity in individual neurons. When INaP and ICAN are removed pharmacologically, the rhythm can be maintained by boosting neural excitability, which is inconsistent with a pacemaker-essential mechanism of respiratory rhythmogenesis by the pre-Botzinger complex

Fishery-Independent Data Reveal Negative Effect of Human Population Density on Caribbean Predatory Fish Communities

BACKGROUND: Understanding the current status of predatory fish communities, and the effects fishing has on them, is vitally important information for management. However, data are often insufficient at region-wide scales to assess the effects of extraction in coral reef ecosystems of developing nations. METHODOLOGY/PRINCIPAL FINDINGS: Here, I overcome this difficulty by using a publicly accessible, fisheries-independent database to provide a broad scale, comprehensive analysis of human impacts on predatory reef fish communities across the greater Caribbean region. Specifically, this study analyzed presence and diversity of predatory reef fishes over a gradient of human population density. Across the region, as human population density increases, presence of large-bodied fishes declines, and fish communities become dominated by a few smaller-bodied species. CONCLUSIONS/SIGNIFICANCE: Complete disappearance of several large-bodied fishes indicates ecological and local extinctions have occurred in some densely populated areas. These findings fill a fundamentally important gap in our knowledge of the ecosystem effects of artisanal fisheries in developing nations, and provide support for multiple approaches to data collection where they are commonly unavailable

Genome remodelling in a basal-like breast cancer metastasis and xenograft

Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumor progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumor, a brain metastasis, and a xenograft derived from the primary tumor. The metastasis contained two de novo mutations and a large deletion not present in the primary tumor, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumor mutations, and displayed a mutation enrichment pattern that paralleled the metastasis (16 of 20 genes). Two overlapping large deletions, encompassing CTNNA1, were present in all three tumor samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared to the primary tumor suggest that secondary tumors may arise from a minority of cells within the primary

Priorities for synthesis research in ecology and environmental science

ACKNOWLEDGMENTS We thank the National Science Foundation grant #1940692 for financial support for this workshop, and the National Center for Ecological Analysis and Synthesis (NCEAS) and its staff for logistical support.Peer reviewedPublisher PD

Priorities for synthesis research in ecology and environmental science

ACKNOWLEDGMENTS We thank the National Science Foundation grant #1940692 for financial support for this workshop, and the National Center for Ecological Analysis and Synthesis (NCEAS) and its staff for logistical support.Peer reviewedPublisher PD

Search of the Orion spur for continuous gravitational waves using a loosely coherent algorithm on data from LIGO interferometers

We report results of a wideband search for periodic gravitational waves from isolated neutron stars within the Orion spur towards both the inner and outer regions of our Galaxy. As gravitational waves interact very weakly with matter, the search is unimpeded by dust and concentrations of stars. One search disk (A) is 6.87° in diameter and centered on 20h10m54.71s+33°33′25.29′′, and the other (B) is 7.45° in diameter and centered on 8h35m20.61s-46°49′25.151′′. We explored the frequency range of 50-1500 Hz and frequency derivative from 0 to -5×10-9 Hz/s. A multistage, loosely coherent search program allowed probing more deeply than before in these two regions, while increasing coherence length with every stage. Rigorous follow-up parameters have winnowed the initial coincidence set to only 70 candidates, to be examined manually. None of those 70 candidates proved to be consistent with an isolated gravitational-wave emitter, and 95% confidence level upper limits were placed on continuous-wave strain amplitudes. Near 169 Hz we achieve our lowest 95% C.L. upper limit on the worst-case linearly polarized strain amplitude h0 of 6.3×10-25, while at the high end of our frequency range we achieve a worst-case upper limit of 3.4×10-24 for all polarizations and sky locations. © 2016 American Physical Society

Genome remodelling in a basal-like breast cancer metastasis and xenograft

Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo mutations and a large deletion not present in the primary tumour, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumour mutations and displayed a mutation enrichment pattern that resembled the metastasis. Two overlapping large deletions, encompassing CTNNA1, were present in all three tumour samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within the primary tumour

All-sky search for long-duration gravitational wave transients with initial LIGO

We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10–500 s in a frequency band of 40–1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4×10[superscript -5] and 9.4×10[superscript -4]  Mpc[superscript -3] yr[superscript -1] at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves.Carnegie TrustDavid & Lucile Packard FoundationAlfred P. Sloan FoundationNational Science Foundation (U.S.

First low frequency all-sky search for continuous gravitational wave signals

In this paper we present the results of the first low frequency all-sky search of continuous gravitational wave signals conducted on Virgo VSR2 and VSR4 data. The search covered the full sky, a frequency range between 20 and 128 Hz with a range of spin-down between −1.0×10−10 and +1.5×10−11  Hz/s, and was based on a hierarchical approach. The starting point was a set of short fast Fourier transforms, of length 8192 s, built from the calibrated strain data. Aggressive data cleaning, in both the time and frequency domains, has been done in order to remove, as much as possible, the effect of disturbances of instrumental origin. On each data set a number of candidates has been selected, using the FrequencyHough transform in an incoherent step. Only coincident candidates among VSR2 and VSR4 have been examined in order to strongly reduce the false alarm probability, and the most significant candidates have been selected. The criteria we have used for candidate selection and for the coincidence step greatly reduce the harmful effect of large instrumental artifacts. Selected candidates have been subject to a follow-up by constructing a new set of longer fast Fourier transforms followed by a further incoherent analysis, still based on the FrequencyHough transform. No evidence for continuous gravitational wave signals was found, and therefore we have set a population-based joint VSR2-VSR4 90% confidence level upper limit on the dimensionless gravitational wave strain in the frequency range between 20 and 128 Hz. This is the first all-sky search for continuous gravitational waves conducted, on data of ground-based interferometric detectors, at frequencies below 50 Hz. We set upper limits in the range between about 10−24 and 2×10−23 at most frequencies. Our upper limits on signal strain show an improvement of up to a factor of ∼2 with respect to the results of previous all-sky searches at frequencies below 80 H

Search of the Orion spur for continuous gravitational waves using a loosely coherent algorithm on data from LIGO interferometers

We report results of a wideband search for periodic gravitational waves from isolated neutron stars within the Orion spur towards both the inner and outer regions of our Galaxy. As gravitational waves interact very weakly with matter, the search is unimpeded by dust and concentrations of stars. One search disk (A) is 6.87° in diameter and centered on 20[superscript h]10[superscript m]54.71[superscript s] + 33°33[superscript ′]25.29[superscript ′′], and the other (B) is 7.45° in diameter and centered on 8[superscript h]35[superscript m]20.61[superscript s] - 46°49[superscript ′]25.151[superscript ′′]. We explored the frequency range of 50–1500 Hz and frequency derivative from 0 to -5 × 10[superscript -9]  Hz/s. A multistage, loosely coherent search program allowed probing more deeply than before in these two regions, while increasing coherence length with every stage. Rigorous follow-up parameters have winnowed the initial coincidence set to only 70 candidates, to be examined manually. None of those 70 candidates proved to be consistent with an isolated gravitational-wave emitter, and 95% confidence level upper limits were placed on continuous-wave strain amplitudes. Near 169 Hz we achieve our lowest 95% C.L. upper limit on the worst-case linearly polarized strain amplitude h[subscript 0] of 6.3 × 10[superscript -25], while at the high end of our frequency range we achieve a worst-case upper limit of 3.4 × 10[superscript -24] for all polarizations and sky locations.National Science Foundation (U.S.)United States. National Aeronautics and Space AdministrationCarnegie TrustDavid & Lucile Packard FoundationAlfred P. Sloan Foundatio