Continuous estimate of Atlantic oceanic freshwater flux at 26.5°N

The first continuous estimates of freshwater flux across 26.5°N are calculated using observations from the RAPID–MOCHA–Western Boundary Time Series (WBTS) and Argo floats every 10 days between April 2004 and October 2012. The mean plus or minus the standard deviation of the freshwater flux (FW) is −1.17 ± 0.20 Sv (1 Sv ≡ 106 m3 s−1; negative flux is southward), implying a freshwater divergence of −0.37 ± 0.20 Sv between the Bering Strait and 26.5°N. This is in the sense of an input of 0.37 Sv of freshwater into the ocean, consistent with a region where precipitation dominates over evaporation. The sign and the variability of the freshwater divergence are dominated by the overturning component (−0.78 ± 0.21 Sv). The horizontal component of the freshwater divergence is smaller, associated with little variability and positive (0.35 ± 0.04 Sv). A linear relationship, describing 91% of the variance, exists between the strength of the meridional overturning circulation (MOC) and the freshwater flux (−0.37 − 0.047 Sv of FW per Sverdrups of MOC). The time series of the residual to this relationship shows a small (0.02 Sv in 8.5 yr) but detectable decrease in the freshwater flux (i.e., an increase in the southward freshwater flux) for a given MOC strength. Historical analyses of observations at 24.5°N are consistent with a more negative freshwater divergence from −0.03 to −0.37 Sv since 1974. This change is associated with an increased southward freshwater flux at this latitude due to an increase in the Florida Straits salinity (and therefore the northward salinity flux)

Simultaneous disruption of two DNA polymerases, Polη and Polζ, in Avian DT40 cells unmasks the role of Polη in cellular response to various DNA lesions

Replicative DNA polymerases are frequently stalled by DNA lesions. The resulting replication blockage is released by homologous recombination (HR) and translesion DNA synthesis (TLS). TLS employs specialized TLS polymerases to bypass DNA lesions. We provide striking in vivo evidence of the cooperation between DNA polymerase η, which is mutated in the variant form of the cancer predisposition disorder xeroderma pigmentosum (XP-V), and DNA polymerase ζ by generating POLη−/−/POLζ−/− cells from the chicken DT40 cell line. POLζ−/− cells are hypersensitive to a very wide range of DNA damaging agents, whereas XP-V cells exhibit moderate sensitivity to ultraviolet light (UV) only in the presence of caffeine treatment and exhibit no significant sensitivity to any other damaging agents. It is therefore widely believed that Polη plays a very specific role in cellular tolerance to UV-induced DNA damage. The evidence we present challenges this assumption. The phenotypic analysis of POLη−/−/POLζ−/− cells shows that, unexpectedly, the loss of Polη significantly rescued all mutant phenotypes of POLζ−/− cells and results in the restoration of the DNA damage tolerance by a backup pathway including HR. Taken together, Polη contributes to a much wide range of TLS events than had been predicted by the phenotype of XP-V cells

Nanotools for Neuroscience and Brain Activity Mapping

Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations in current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and others refer to this goal as the Brain Activity Mapping Project. In this Nano Focus, we discuss how recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience. These approaches represent exciting areas of technical development and research. Moreover, unique opportunities exist for nanoscientists, nanotechnologists, and other physical scientists and engineers to contribute to tackling the challenging problems involved in understanding the fundamentals of brain function

The scientific and societal uses of global measurements of subsurface velocity

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Szuts, Z. B., Bower, A. S., Donohue, K. A., Girton, J. B., Hummon, J. M., Katsumata, K., Lumpkin, R., Ortner, P. B., Phillips, H. E., Rossby, H. T., Shay, L. K., Sun, C., & Todd, R. E. The scientific and societal uses of global measurements of subsurface velocity. Frontiers in Marine Science, 6, (2019): 358, doi:10.3389/fmars.2019.00358.Ocean velocity defines ocean circulation, yet the available observations of subsurface velocity are under-utilized by society. The first step to address these concerns is to improve visibility of and access to existing measurements, which include acoustic sampling from ships, subsurface float drifts, and measurements from autonomous vehicles. While multiple programs provide data publicly, the present difficulty in finding, understanding, and using these data hinder broader use by managers, the public, and other scientists. Creating links from centralized national archives to project specific websites is an easy but important way to improve data discoverability and access. A further step is to archive data in centralized databases, which increases usage by providing a common framework for disparate measurements. This requires consistent data standards and processing protocols for all types of velocity measurements. Central dissemination will also simplify the creation of derived products tailored to end user goals. Eventually, this common framework will aid managers and scientists in identifying regions that need more sampling and in identifying methods to fulfill those demands. Existing technologies are capable of improving spatial and temporal sampling, such as using ships of opportunity or from autonomous platforms like gliders, profiling floats, or Lagrangian floats. Future technological advances are needed to fill sampling gaps and increase data coverage.This work was supported by the National Science Foundation, United States, Grant Numbers 1356383 to ZBS, OCE 1756361 to ASB at the Woods Hole Oceanographic Institution, and 1536851 to KAD and HTR; the National Oceanographic and Atmospheric Administration, United States, Ocean Observations and Monitoring Division and Atlantic Oceanographic and Meteorological Laboratory to RL; Royal Caribbean Cruise Ltd., to PBO; the Australian Government Department of the Environment and Energy National Environmental Science Programme and Australian Research Council Centre of Excellence for Climate Extremes to HEP; and the Gulf of Mexico Research Initiative Grant V-487 to LS

hMMS2 serves a redundant role in human PCNA polyubiquitination

<p>Abstract</p> <p>Background</p> <p>In yeast, DNA damage leads to the mono and polyubiquitination of the sliding clamp PCNA. Monoubiquitination of PCNA is controlled by RAD18 (E3 ligase) and RAD6 (E2 conjugating enzyme), while the extension of the monoubiquitinated PCNA into a polyubiquitinated substrate is governed by RAD5, and the heterodimer of UBC13/MMS2. Each modification directs a different branch of the DNA damage tolerance pathway (DDT). While PCNA monoubiquitination leads to error-prone bypass via TLS, biochemical studies have identified MMS2 along with its heteromeric partner UBC13 to govern the error-free repair of DNA lesions by catalyzing the formation of lysine 63-linked polyubiquitin chains (K63-polyUb). Recently, it was shown that PCNA polyubiquitination is conserved in human cells and that this modification is dependent on RAD18, UBC13 and SHPRH. However, the role of hMMS2 in this process was not specifically addressed.</p> <p>Results</p> <p>In this report we show that mammalian cells in which MMS2 was reduced by siRNA-mediated knockdown maintains PCNA polyubiquitination while a knockdown of RAD18 or UBC13 abrogates PCNA ubiquitination. Moreover, the additional knockdown of a UEV1A (MMS2 homolog) does not deplete PCNA polyubiquitination. Finally, mouse embryonic stem cells null for MMS2 with or without the additional depletion of mUEV1A continue to polyubiquitinated PCNA with normal kinetics.</p> <p>Conclusion</p> <p>Our results point to a high level of redundancy in the DDT pathway and suggest the existence of another hMMS2 variant (hMMSv) or complex that can compensate for its loss.</p

Frequent CHD1 Deletions in Prostate Cancers of African American Men Is Associated With Rapid Disease Progression

We analyzed genomic data from the prostate cancer of African- and European American men to identify differences contributing to racial disparity of outcome. We also performed FISH-based studies of Chromodomain helicase DNA-binding protein 1 (CHD1) loss on prostate cancer tissue microarrays. We created CHD1-deficient prostate cancer cell lines for genomic, drug sensitivity and functional homologous recombination (HR) activity analysis. Subclonal deletion of CHD1 was nearly three times as frequent in prostate tumors of African American than in European American men and it associates with rapid disease progression. CHD1 deletion was not associated with HR deficiency associated mutational signatures or HR deficiency as detected by RAD51 foci formation. This was consistent with the moderate increase of olaparib and talazoparib sensitivity with several CHD1 deficient cell lines showing talazoparib sensitivity in the clinically relevant concentration range. CHD1 loss may contribute to worse disease outcome in African American men

Linking mixing processes and climate variability to the heat content distribution of the Eastern Mediterranean abyss

The heat contained in the ocean (OHC) dominates the Earth’s energy budget and hence represents a fundamental parameter for understanding climate changes. However, paucity of observational data hampers our knowledge on OHC variability, particularly in abyssal areas. Here, we analyze water characteristics, observed during the last three decades in the abyssal Ionian Sea (Eastern Mediterranean), where two competing convective sources of bottom water exist. We find a heat storage of ~1.6 W/m2– twice that assessed globally in the same period – exceptionally well-spread throughout the local abyssal layers. Such an OHC accumulation stems from progressive warming and salinification of the Eastern Mediterranean, producing warmer near-bottom waters. We analyze a new process that involves convectively-generated waters reaching the abyss as well as the triggering of a diapycnal mixing due to rough bathymetry, which brings to a warming and thickening of the bottom layer, also influencing water-column potential vorticity. This may affect the prevailing circulation, altering the local cyclonic/anticyclonic long-term variability and hence precondition future water-masses formation and the redistribution of heat along the entire water-column

A wireless multi-channel neural amplifier for freely moving animals

Conventional neural recording systems restrict behavioral experiments to a flat indoor environment compatible with the cable that tethers the subject to recording instruments. To overcome these constraints, we developed a wireless multi-channel system for recording neural signals from rats. The device takes up to 64 voltage signals from implanted electrodes, samples each at 20 kHz, time-division multiplexes them into one signal and transmits that output by radio frequency to a receiver up to 60 m away. The system introduces <4 μV of electrode-referred noise, comparable to wired recording systems, and outperforms existing rodent telemetry systems in channel count, weight and transmission range. This allows effective recording of brain signals in freely behaving animals. We report measurements of neural population activity taken outdoors and in tunnels. Neural firing in the visual cortex was relatively sparse, correlated even across large distances and was strongly influenced by locomotor activity

Wnt, Hedgehog and Junctional Armadillo/β-Catenin Establish Planar Polarity in the Drosophila Embryo

To generate specialized structures, cells must obtain positional and directional information. In multi-cellular organisms, cells use the non-canonical Wnt or planar cell polarity (PCP) signaling pathway to establish directionality within a cell. In vertebrates, several Wnt molecules have been proposed as permissible polarity signals, but none has been shown to provide a directional cue. While PCP signaling components are conserved from human to fly, no PCP ligands have been reported in Drosophila. Here we report that in the epidermis of the Drosophila embryo two signaling molecules, Hedgehog (Hh) and Wingless (Wg or Wnt1), provide directional cues that induce the proper orientation of Actin-rich structures in the larval cuticle. We further find that proper polarity in the late embryo also involves the asymmetric distribution and phosphorylation of Armadillo (Arm or β-catenin) at the membrane and that interference with this Arm phosphorylation leads to polarity defects. Our results suggest new roles for Hh and Wg as instructive polarizing cues that help establish directionality within a cell sheet, and a new polarity-signaling role for the membrane fraction of the oncoprotein Arm