In 1990, Andrew Bakun proposed that increasing greenhouse gas concentrations would force intensification of upwelling-favorable winds in eastern boundary current systems that contribute substantial ...services to society. Because there is considerable disagreement about whether contemporary wind trends support Bakun's hypothesis, we performed a meta-analysis of the literature on upwelling-favorable wind intensification. The preponderance of published analyses suggests that winds have intensified in the California, Benguela, and Humboldt upwelling systems and weakened in the Iberian system over time scales ranging up to 60 years; wind change is equivocal in the Canary system. Stronger intensification signals are observed at higher latitudes, consistent with the warming pattern associated with climate change. Overall, reported changes in coastal winds, although subtle and spatially variable, support Bakun's hypothesis of upwelling intensification in eastern boundary current systems.
Alongshore wind speed and sea surface temperature (SST) from coastal National Data Buoy Center buoys are used to study the variability of wind‐driven coastal upwelling from 1982 to 2008. A long‐term ...increase in upwelling is observed in central California (35°N–39°N) with stronger upwelling‐favorable winds, colder water, and more frequent occurrences of upwelling days during the upwelling season (March–July). Further, a longer upwelling season is observed in the same region, starting earlier in the spring and persisting later in the fall. These interannual changes in upwelling strength and seasonal duration are investigated in this study. Changes in alongshore wind (forcing of upwelling) are poorly correlated with the El Niño–Southern Oscillation or the Pacific Decadal Oscillation, but the Northern Oscillation and the North Pacific Gyre Oscillation correlate with the geostrophic upwelling‐favorable winds in the region. However, changes in SST (an upwelling response) are correlated with both changes in wind (upwelling forcing) and the climate indices. Although this short record cannot differentiate between multidecadal cycles and persistent trends, this data‐based result does corroborate model‐based projections of increased upwelling in this region due to global climate change. This increase in upwelling is understood to be a response to the strengthening of large‐scale pressure gradient fields partially due to global‐scale climate change. Farther north and farther south in California, other processes also have a significant influence on coastal conditions, such that the tendency for increased upwelling is not evident in the same way.
The coastal ocean environment off California is largely determined by wind‐driven coastal upwelling, with an ecosystem that is tightly coupled to seasonality in this upwelling. Three decades of data ...measured over the California shelf at NOAA buoys are used to describe the seasonal variability of the winds that force upwelling and the response of the coastal ocean in terms of sea temperature. Moreover, seasonal patterns in surface chlorophyll and alongshore currents are determined from one decade of data. In addition to clear seasonality, all these data exhibit distinct spatial and non‐seasonal temporal variability in upwelling. Based on alongshore wind stress characteristics in central and north California, three seasons are defined: Upwelling Season (April‐June) with strong upwelling‐favorable winds and large standard deviation due to frequent reversals; Relaxation Season (July‐September) with weak equatorward winds and low variability; and Storm Season (December‐February) characterized by weak mean wind stress but large variability. The remaining months are transitional, falling into one or other season in different years. In addition to large‐scale latitudinal differences in wind stress, spatial differences are associated with coastal topography ‐ specifically the acceleration of wind downstream of capes. Latitudinal differences in sea surface temperature depend on wind stress, both local and large‐scale, but also on surface heating and offshore influences. Intra‐annual and inter‐annual anomalies in wind and sea surface temperature are associated with variability in coastal winds, large‐scale winds, and offshore basin‐scale ocean conditions. Satellite chlorophyll concentration shows an optimal window relation with upwelling forcing, allowing maximum concentrations during moderate winds and minimal during poor or strong winds.
Key Points
Three seasons defined from coastal winds: upwelling, relaxation, and storm
Coastal winds driven by large‐scale winds and modified by local topography
Upwelling variability associated to winds and basin‐scale ocean conditions
The executive functions allow for purposeful, deliberate, and intentional interactions with the world-attention and focus, impulse control, decision making, and working memory. These measures have ...been correlated with academic outcomes and quality of life, and are impacted by deleterious environmental events throughout the life span, including gestational and early life insults. This review will address the topic of sex differences in executive function including a discussion of differences arising in response to developmental programming. Work on gender differences in human studies and sex differences in animal research will be reviewed. Overall, we find little support for significant gender or sex differences in executive function. An important variable that factors into the interpretation of potential sex differences include differing developmental trajectories. We conclude by discussing future directions for the field and a brief discussion of biological mechanisms.
Apoptosis is an evolutionary conserved homeostatic process involved in distinct physiological processes including organ and tissue morphogenesis, development and senescence. Its deregulation is also ...known to participate in the etiology of several human diseases including cancer, neurodegenerative and autoimmune disorders. Environmental stressors (cytotoxic agents, pollutants or toxicants) are well known to induce apoptotic cell death and to contribute to a variety of pathological conditions. Oxidative stress seems to be the central element in the regulation of the apoptotic pathways triggered by environmental stressors. In this work, we review the established mechanisms by which oxidative stress and environmental stressors regulate the apoptotic machinery with the aim to underscore the relevance of apoptosis as a component in environmental toxicity and human disease progression.
Graphene is an excellent material for long-distance spin transport but allows little spin manipulation. Transition-metal dichalcogenides imprint their strong spin–orbit coupling into graphene via the ...proximity effect, and it has been predicted that efficient spin-to-charge conversion due to spin Hall and Rashba–Edelstein effects could be achieved. Here, by combining Hall probes with ferromagnetic electrodes, we unambiguously demonstrate experimentally the spin Hall effect in graphene induced by MoS2 proximity and for varying temperatures up to room temperature. The fact that spin transport and the spin Hall effect occur in different parts of the same material gives rise to a hitherto unreported efficiency for the spin-to-charge voltage output. Additionally, for a single graphene/MoS2 heterostructure-based device, we evidence a superimposed spin-to-charge current conversion that can be indistinguishably associated with either the proximity-induced Rashba–Edelstein effect in graphene or the spin Hall effect in MoS2. By a comparison of our results to theoretical calculations, the latter scenario is found to be the most plausible one. Our findings pave the way toward the combination of spin information transport and spin-to-charge conversion in two-dimensional materials, opening exciting opportunities in a variety of future spintronic applications.
Nonadherence to immunosuppressant medications is a leading cause of poor long‐term outcomes in transplant recipients. The Medication Level Variability Index (MLVI) provides a vehicle for transplant ...outcome risk‐stratification through continuous assessment of adherence. The MALT (Medication Adherence in children who had a Liver Transplant) prospective multi‐site study evaluated whether MLVI predicts late acute rejection (LAR). Four hundred pediatric (1–17‐year‐old) liver transplant recipients were enrolled and followed for 2 years. The a‐priori hypothesis was that a higher MLVI predicts LAR. Predefined secondary analyses evaluated other outcomes such as liver enzyme levels, and sensitivity analyses compared adolescents to pre‐adolescents. In the primary analysis sample of 379 participants, a higher prerejection MLVI predicted LAR (mean prerejection MLVI with LAR: 2.4 3.6 standard deviation versus without LAR, 1.6 1.1; p = 0.026). Fifty‐three percent of the adolescents with MLVI>2 in year 1 had LAR by the end of year 2, as compared with 6% of those with year 1 MLVI≤2. A higher MLVI was significantly associated with all secondary outcomes. MLVI, a marker of medication adherence that uses clinically derived information, predicts LAR in pediatric liver transplant recipients.
The medication level variability index, a measure of adherence to immunosuppressant medications, predicts late acute rejection and liver injury, and may be used to stratify risk and inform interventions before adverse outcomes occur in pediatric liver transplant recipients.
Inflammasomes are cytosolic multiprotein complexes that initiate host defense against bacterial pathogens by activating caspase-1–dependent cytokine secretion and cell death. In mice, specific ...nucleotide-binding domain, leucine-rich repeat-containing family, apoptosis inhibitory proteins (NAIPs) activate the nucleotide-binding domain, leucine-rich repeat-containing family, CARD domain-containing protein 4 (NLRC4) inflammasome upon sensing components of the type III secretion system (T3SS) and flagellar apparatus. NAIP1 recognizes the T3SS needle protein, NAIP2 recognizes the T3SS inner rod protein, and NAIP5 and NAIP6 recognize flagellin. In contrast, humans encode a single functional NAIP, raising the question of whether human NAIP senses one or multiple bacterial ligands. Previous studies found that human NAIP detects both flagellin and the T3SS needle protein and suggested that the ability to detect both ligands was achieved by multiple isoforms encoded by the single human NAIP gene. Here, we show that human NAIP also senses the Salmonella Typhimurium T3SS inner rod protein PrgJ and that T3SS inner rod proteins from multiple bacterial species are also detected. Furthermore, we show that a single human NAIP isoform is capable of sensing the T3SS inner rod, needle, and flagellin. Our findings indicate that, in contrast to murine NAIPs, promiscuous recognition of multiple bacterial ligands is conferred by a single human NAIP.
Alphaproteobacteria commonly produce an adhesin that is anchored to the exterior of the envelope at one cell pole. In Caulobacter crescentus this adhesin, known as the holdfast, facilitates ...attachment to solid surfaces and cell partitioning to air-liquid interfaces. An ensemble of two-component signal transduction (TCS) proteins controls C. crescentus holdfast biogenesis by indirectly regulating expression of HfiA, a potent inhibitor of holdfast synthesis. We performed a genetic selection to discover direct hfiA regulators that function downstream of the adhesion TCS system and identified rtrC, a hypothetical gene. rtrC transcription is directly activated by the adhesion TCS regulator, SpdR. Though its primary structure bears no resemblance to any defined protein family, RtrC binds and regulates dozens of sites on the C. crescentus chromosome via a pseudo-palindromic sequence. Among these binding sites is the hfiA promoter, where RtrC functions to directly repress transcription and thereby activate holdfast development. Either RtrC or SpdR can directly activate transcription of a second hfiA repressor, rtrB. Thus, environmental regulation of hfiA transcription by the adhesion TCS system is subject to control by an OR-gated type I coherent feedforward loop; these regulatory motifs are known to buffer gene expression against fluctuations in regulating signals. We have further assessed the functional role of rtrC in holdfast-dependent processes, including surface adherence to a cellulosic substrate and formation of pellicle biofilms at air-liquid interfaces. Strains harboring insertional mutations in rtrC have a diminished adhesion profile in a competitive cheesecloth binding assay and a reduced capacity to colonize pellicle biofilms in select media conditions. Our results add to an emerging understanding of the regulatory topology and molecular components of a complex bacterial cell adhesion control system.
AS1411 is a 26-mer G-rich DNA oligonucleotide that forms a variety of G-quadruplex structures. It was identified based on its cancer-selective antiproliferative activity and subsequently determined ...to be an aptamer to nucleolin, a multifunctional protein that preferentially binds quadruplex nucleic acids and which is present at high levels on the surface of cancer cells. AS1411 has exceptionally efficient cellular internalization compared to non-quadruplex DNA sequences.
Recent developments related to AS1411 will be examined, with a focus on its use for targeted delivery of therapeutic and imaging agents.
Numerous research groups have used AS1411 as a targeting agent to deliver nanoparticles, oligonucleotides, and small molecules into cancer cells. Studies in animal models have demonstrated that AS1411-linked materials can accumulate selectively in tumors following systemic administration. The mechanism underlying the cancer-targeting ability of AS1411 is not completely understood, but recent studies suggest a model that involves: (1) initial uptake by macropinocytosis, a form of endocytosis prevalent in cancer cells; (2) stimulation of macropinocytosis by a nucleolin-dependent mechanism resulting in further uptake; and (3) disruption of nucleolin-mediated trafficking and efflux leading to cargoes becoming trapped inside cancer cells.
Human trials have indicated that AS1411 is safe and can induce durable remissions in a few patients, but new strategies are needed to maximize its clinical impact. A better understanding of the mechanisms by which AS1411 targets and kills cancer cells may hasten the development of promising technologies using AS1411-linked nanoparticles or conjugates for cancer-targeted therapy and imaging. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.
•AS1411 is a G-quadruplex DNA oligonucleotide that is also a nucleolin aptamer.•This review covers the structure, clinical status, uses, and mechanism of AS1411.•AS1411 is being widely used to deliver therapeutic and imaging agents to cancer cells.•Its cancer-targeting activity has been demonstrated in at least 30 animal studies.•Its targeting mechanism is not fully understood but may involve macropinocytosis.
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