Marine heatwaves drive recurrent mass mortalities in the Mediterranean Sea.

Climate change is causing an increase in the frequency and intensity of marine heatwaves (MHWs) and mass mortality events (MMEs) of marine organisms are one of their main ecological impacts. Here, we show that during the 2015-2019 period, the Mediterranean Sea has experienced exceptional thermal conditions resulting in the onset of five consecutive years of widespread MMEs across the basin. These MMEs affected thousands of kilometers of coastline from the surface to 45 m, across a range of marine habitats and taxa (50 taxa across 8 phyla). Significant relationships were found between the incidence of MMEs and the heat exposure associated with MHWs observed both at the surface and across depths. Our findings reveal that the Mediterranean Sea is experiencing an acceleration of the ecological impacts of MHWs which poses an unprecedented threat to its ecosystems' health and functioning. Overall, we show that increasing the resolution of empirical observation is critical to enhancing our ability to more effectively understand and manage the consequences of climate change.

What and where? Predicting invasion hotspots in the Arctic marine realm.

The risk of aquatic invasions in the Arctic is expected to increase with climate warming, greater shipping activity and resource exploitation in the region. Planktonic and benthic marine aquatic invasive species (AIS) with the greatest potential for invasion and impact in the Canadian Arctic were identified and the 23 riskiest species were modelled to predict their potential spatial distributions at pan-Arctic and global scales. Modelling was conducted under present environmental conditions and two intermediate future (2050 and 2100) global warming scenarios. Invasion hotspots-regions of the Arctic where habitat is predicted to be suitable for a high number of potential AIS-were located in Hudson Bay, Northern Grand Banks/Labrador, Chukchi/Eastern Bering seas and Barents/White seas, suggesting that these regions could be more vulnerable to invasions. Globally, both benthic and planktonic organisms showed a future poleward shift in suitable habitat. At a pan-Arctic scale, all organisms showed suitable habitat gains under future conditions. However, at the global scale, habitat loss was predicted in more tropical regions for some taxa, particularly most planktonic species. Results from the present study can help prioritize management efforts in the face of climate change in the Arctic marine ecosystem. Moreover, this particular approach provides information to identify present and future high-risk areas for AIS in response to global warming.

Structural and Electronic Flexibility in Hydrides of Zintl Phases with Tetrel-Hydrogen and Tetrel-Tetrel Bonds.

The hydrogenation of Zintl phases enables the formation of new structural entities with main-group-element-hydrogen bonds in the solid state. The hydrogenation of SrSi, BaSi, and BaGe yields the hydrides SrSiH5/3-x, BaSiH5/3-x and BaGeH5/3-x . The crystal structures show a sixfold superstructure compared to the parent Zintl phase and were solved by a combination of X-ray, neutron, and electron diffraction and the aid of DFT calculations. Layers of connected HSr4 (HBa4 ) tetrahedra containing hydride ions alternate with layers of infinite single- and double-chain polyanions, in which hydrogen atoms are covalently bound to silicon and germanium. The idealized formulae AeTtH5/3 (Ae=alkaline earth, Tt=tetrel) can be rationalized with the Zintl-Klemm concept according to (Ae2+ )3 (TtH- )(Tt2 H2- )(H- )3 , where all Tt atoms are three-binding. The non-stoichiometry (SrSiH5/3-x , x=0.17(2); BaGeH5/3-x , x=0.10(3)) can be explained by additional π-bonding of the Tt chains.

COT drives resistance to RAF inhibition through MAP kinase pathway reactivation.

Oncogenic mutations in the serine/threonine kinase B-RAF (also known as BRAF) are found in 50-70% of malignant melanomas. Pre-clinical studies have demonstrated that the B-RAF(V600E) mutation predicts a dependency on the mitogen-activated protein kinase (MAPK) signalling cascade in melanoma-an observation that has been validated by the success of RAF and MEK inhibitors in clinical trials. However, clinical responses to targeted anticancer therapeutics are frequently confounded by de novo or acquired resistance. Identification of resistance mechanisms in a manner that elucidates alternative 'druggable' targets may inform effective long-term treatment strategies. Here we expressed ∼600 kinase and kinase-related open reading frames (ORFs) in parallel to interrogate resistance to a selective RAF kinase inhibitor. We identified MAP3K8 (the gene encoding COT/Tpl2) as a MAPK pathway agonist that drives resistance to RAF inhibition in B-RAF(V600E) cell lines. COT activates ERK primarily through MEK-dependent mechanisms that do not require RAF signalling. Moreover, COT expression is associated with de novo resistance in B-RAF(V600E) cultured cell lines and acquired resistance in melanoma cells and tissue obtained from relapsing patients following treatment with MEK or RAF inhibitors. We further identify combinatorial MAPK pathway inhibition or targeting of COT kinase activity as possible therapeutic strategies for reducing MAPK pathway activation in this setting. Together, these results provide new insights into resistance mechanisms involving the MAPK pathway and articulate an integrative approach through which high-throughput functional screens may inform the development of novel therapeutic strategies.

Silver Indium Telluride Semiconductors and Their Solid Solutions with Cadmium Indium Telluride: Structure and Physical Properties.

Ag0.8In2.4Te4 (= AgIn3Te5) and Ag0.5In2.5Te4 (= AgIn5Te8) form solid solutions with CdIn2Te4, which are interesting as materials for photovoltaics or with respect to their thermoelectric properties. The corresponding crystal structures are related to the chalcopyrite type. Rietveld refinements of high-resolution synchrotron powder diffraction data measured at K-absorption edges of Cd, Ag, In, and Te and electron diffraction reveal the symmetry as well as the element and vacancy distribution in Ag0.8In2.4Te4 (= AgIn3Te5)/Ag0.5In2.5Te4 (= AgIn5Te8) mixed crystals such as Ag0.25Cd0.5In2.25Te4 and Ag0.2Cd0.75In2.1Te4. All compounds of the solid solution series (CdIn2Te4)x(Ag0.5In2.5Te4)1-x exhibit the HgCu2I4 structure type (space group I4̅2m) with completely ordered vacancies but disordered cations. The uniform cation distribution and thus the local charge balance are comparable to that of CdIn2Te4. In contrast, Ag0.8In2.4Te4 (= AgIn3Te5) crystallizes in the space group P4̅2c with disordered cations and partially ordered vacancies. This is corroborated by bond-valence sum calculations and the fact that there is a Vegard-like behavior for compounds with 0.5 < x in the pseudobinary system (CdIn2Te4)x(Ag0.8In2.4Te4)1-x. Owing to the different structures, there is no complete solid solution series between CdIn2Te4 and AgIn3Te5. All compounds in this work are n-type semiconductors with a low electrical conductivity (∼1 S/m) and rather high absolute Seebeck coefficients (up to -750 µV/mK; 225 °C). Electrical band gaps (Eg) determined from the Seebeck coefficients as well as (more reliably) from the electrical conductivity range between 0.19 and 1.13 eV.

Maintenance of adenomatous polyposis coli (APC)-mutant colorectal cancer is dependent on Wnt/beta-catenin signaling.

Persistent expression of certain oncogenes is required for tumor maintenance. This phenotype is referred to as oncogene addiction and has been clinically validated by anticancer therapies that specifically inhibit oncoproteins such as BCR-ABL, c-Kit, HER2, PDGFR, and EGFR. Identifying additional genes that are required for tumor maintenance may lead to new targets for anticancer drugs. Although the role of aberrant Wnt pathway activation in the initiation of colorectal cancer has been clearly established, it remains unclear whether sustained Wnt pathway activation is required for colorectal tumor maintenance. To address this question, we used inducible ß-catenin shRNAs to temporally control Wnt pathway activation in vivo. Here, we show that active Wnt/ß-catenin signaling is required for maintenance of colorectal tumor xenografts harboring APC mutations. Reduced tumor growth upon ß-catenin inhibition was due to cell cycle arrest and differentiation. Upon reactivation of the Wnt/ß-catenin pathway colorectal cancer cells resumed proliferation and reacquired a crypt progenitor phenotype. In human colonic adenocarcinomas, high levels of nuclear ß-catenin correlated with crypt progenitor but not differentiation markers, suggesting that the Wnt/ß-catenin pathway may also control colorectal tumor cell fate during the maintenance phase of tumors in patients. These results support efforts to treat human colorectal cancer by pharmacological inhibition of the Wnt/ß-catenin pathway.

Productivity of mixed kelp communities in an Arctic fjord exhibit tolerance to a future climate.

Arctic fjords are considered to be one of the ecosystems changing most rapidly in response to climate change. In the Svalbard archipelago, fjords are experiencing a shift in environmental conditions due to the Atlantification of Arctic waters and the retreat of sea-terminating glaciers. These environmental changes are predicted to facilitate expansion of large, brown macroalgae, into new ice-free regions. The potential resilience of macroalgal benthic communities in these fjord systems will depend on their response to combined pressures from freshening due to glacial melt, exposure to warmer waters, and increased turbidity from meltwater runoff which reduces light penetration. Current predictions, however, have a limited ability to elucidate the future impacts of multiple-drivers on macroalgal communities with respect to ecosystem function and biogeochemical cycling in Arctic fjords. To assess the impact of these combined future environmental changes on benthic productivity and resilience, we conducted a two-month mesocosm experiment exposing mixed kelp communities to three future conditions comprising increased temperature (+ 3.3 and + 5.3°C), seawater freshening by ∼ 3.0 and ∼ 5.0 units (i.e., salinity of 30 and 28, respectively), and decreased photosynthetically active radiation (PAR, - 25 and - 40 %). Exposure to these combined treatments resulted in non-significant differences in short-term productivity, and a tolerance of the photosynthetic capacity across the treatment conditions. We present the first robust estimates of mixed kelp community production in Kongsfjorden and place a median compensation irradiance of ∼12.5 mmol photons m-2 h-1 as the threshold for positive net community productivity. These results are discussed in the context of ecosystem productivity and biological tolerance of kelp communities in future Arctic fjord systems.

Automated Neuropsychological Assessment Metrics (v4) Traumatic Brain Injury Battery: military normative data.

The aim of the present study was to establish normative data for the Automated Neuropsychological Assessment Metrics (v4) Traumatic Brain Injury (ANAM4 TBI) battery in a military context. ANAM4 data from over 107,500 active duty service members ranging from 17 to 65 years of age were included in this study. The influence of the demographic variables of age and gender were also examined. These norms, stratified by age and gender, represent a more comprehensive set of norms than previously available and are provided as a representative set of norms for clinical practice. Additionally, base rates of below average performance in a normal population are provided to help inform clinical decision making.

Effects of military deployment on cognitive functioning.

Military deployment poses many risks for cognitive functioning. When deployed individuals are compared to a nondeployed control group, there is some evidence that deployment may be associated with declines in cognitive functioning. The current study examined cognitive performance before and following deployment in a large sample of active duty military personnel (N = 8002) who reported no traumatic brain injury (TBI). Cognition was assessed using the Automated Neuropsychological Assessment Metrics version 4 TBI Military (ANAM4 TBI-MIL) battery, a computer-based battery of tests measuring attention, processing speed, and general cognitive efficiency. Pre- and postdeployment scores were compared using repeated measures analyses. Although statistically significant differences were observed for all tests (with 5 of 7 tests demonstrating performance improvement), effect sizes were very small for all but 1 test, indicating that performance differences had minimal clinical significance. Likewise, determination of change for individuals using reliable change indices revealed that a very small percentage (<3%) of this presumed healthy sample showed meaningful decline in cognition following deployment. Analyses indicated that despite risks for cognitive decline while in theater, deployment had minimal to no lasting effect on cognition as measured by ANAM4 TBI-Mil upon return from deployment.

A novel approach to quantify metrics of upwelling intensity, frequency, and duration.

The importance of coastal upwelling systems is widely recognized. However, several aspects of the current and future behaviors of these systems remain uncertain. Fluctuations in temperature because of anthropogenic climate change are hypothesized to affect upwelling-favorable winds and coastal upwelling is expected to intensify across all Eastern Boundary Upwelling Systems. To better understand how upwelling may change in the future, it is necessary to develop a more rigorous method of quantifying this phenomenon. In this paper, we use SST data and wind data in a novel method of detecting upwelling signals and quantifying metrics of upwelling intensity, duration, and frequency at four sites within the Benguela Upwelling System. We found that indicators of upwelling are uniformly detected across five SST products for each of the four sites and that the duration of those signals is longer in SST products with higher spatial resolutions. Moreover, the high-resolution SST products are significantly more likely to display upwelling signals at 25 km away from the coast when signals were also detected at the coast. Our findings promote the viability of using SST and wind time series data to detect upwelling signals within coastal upwelling systems. We highlight the importance of high-resolution data products to improve the reliability of such estimates. This study represents an important step towards the development of an objective method for describing the behavior of coastal upwelling systems.

Marine Heatwaves.

Ocean temperature variability is a fundamental component of the Earth's climate system, and extremes in this variability affect the health of marine ecosystems around the world. The study of marine heatwaves has emerged as a rapidly growing field of research, given notable extreme warm-water events that have occurred against a background trend of global ocean warming. This review summarizes the latest physical and statistical understanding of marine heatwaves based on how they are identified, defined, characterized, and monitored through remotely sensed and in situ data sets. We describe the physical mechanisms that cause marine heatwaves, along with their global distribution, variability, and trends. Finally, we discuss current issues in this developing research area, including considerations related to thechoice of climatological baseline periods in defining extremes and how to communicate findings in the context of societal needs.

Aminophospholipid translocase TAT-1 promotes phosphatidylserine exposure during C. elegans apoptosis.

Phospholipids are distributed asymmetrically across the plasma-membrane bilayer of eukaryotic cells: Phosphatidylserine (PS), phosphatidylethanolamine, and phosphoinositides are predominantly restricted to the inner leaflet, whereas phophatidylcholine and sphingolipids are enriched on the outer leaflet [1, 2]. Exposure of PS on the cell surface is a conserved feature of apoptosis and plays an important role in promoting the clearance of apoptotic cells by phagocytosis [3]. However, the molecular mechanism that drives PS exposure remains mysterious. To address this issue, we studied cell-surface changes during apoptosis in the nematode C. elegans. Here, we show that PS exposure can readily be detected on apoptotic C. elegans cells. We generated a transgenic strain expressing a GFP::Annexin V reporter to screen for genes required for this process. Although none of the known engulfment genes was required, RNAi knockdown of the putative aminophospholipid transporter gene tat-1 abrogated PS exposure on apoptotic cells. tat-1(RNAi) also reduced the efficiency of cell-corpse clearance, suggesting that PS exposure acts as an "eat-me" signal in worms. We propose that tat-1 homologs might also play an important role in PS exposure in mammals.

Case report: Treatment of mild traumatic brain injury with hyperbaric oxygen.

Two United States Air Force Airmen were injured in a roadside improvised explosive device (IED) blast in Iraq in January 2008. Both airmen suffered concussive injuries and developed irritability, sleep disturbances, headaches, memory difficulties and cognitive difficulties as symptoms of mild traumatic brain injury (mTBI). Six months after injury, repeat Automated Neuropsychological Assessment Metrics (ANAM) testing showed deterioration, when compared to pre-injury baseline ANAM assessment, in all measured areas (simple reaction time, procedural reaction time, code substitution learning, code substitution delayed, mathematical processing, and matching to sample). The airmen were treated with hyperbaric oxygen in treatments of 100% oxygen for one hour at 1.5 atmospheres absolute, resulting in rapid improvement of headaches and sleep disturbances, improvement in all symptoms and resolution of most symptoms. Repeat ANAM testing after completion of the hyperbaric treatments - nine months after initial injury - showed improvement in all areas, with most measures improving to pre-injury baseline levels. The airmen received no other treatment besides medical monitoring. Repeat neuropsychologic testing confirmed the improvement. We conclude that the improvement in symptoms and ANAM performance is most likely attributable to HBO treatment.

An unexpectedly high degree of specialization and a widespread involvement in sterol metabolism among the C. elegans putative aminophospholipid translocases.

BACKGROUND: P-type ATPases in subfamily IV are exclusively eukaryotic transmembrane proteins that have been proposed to directly translocate the aminophospholipids phosphatidylserine and phosphatidylethanolamine from the exofacial to the cytofacial monolayer of the plasma membrane. Eukaryotic genomes contain many genes encoding members of this subfamily. At present it is unclear why there are so many genes of this kind per organism or what individual roles these genes perform in organism development. RESULTS: We have systematically investigated expression and developmental function of the six, tat-1 through 6, subfamily IV P-type ATPase genes encoded in the Caenorhabditis elegans genome. tat-5 is the only ubiquitously-expressed essential gene in the group. tat-6 is a poorly-transcribed recent duplicate of tat-5. tat-2 through 4 exhibit tissue-specific developmentally-regulated expression patterns. Strong expression of both tat-2 and tat-4 occurs in the intestine and certain other cells of the alimentary system. The two are also expressed in the uterus, during spermatogenesis and in the fully-formed spermatheca. tat-2 alone is expressed in the pharyngeal gland cells, the excretory system and a few cells of the developing vulva. The expression pattern of tat-3 is almost completely different from those of tat-2 and tat-4. tat-3 expression is detectable in the steroidogenic tissues: the hypodermis and the XXX cells, as well as in most cells of the pharynx (except gland), various tissues of the reproductive system (except uterus and spermatheca) and seam cells. Deletion of tat-1 through 4 individually interferes little or not at all with the regular progression of organism growth and development under normal conditions. However, tat-2 through 4 become essential for reproductive growth during sterol starvation. CONCLUSION: tat-5 likely encodes a housekeeping protein that performs the proposed aminophospholipid translocase function routinely. Although individually dispensable, tat-1 through 4 seem to be at most only partly redundant. Expression patterns and the sterol deprivation hypersensitivity deletion phenotype of tat-2 through 4 suggest that these genes carry out subtle metabolic functions, such as fine-tuning sterol metabolism in digestive or steroidogenic tissues. These findings uncover an unexpectedly high degree of specialization and a widespread involvement in sterol metabolism among the genes encoding the putative aminophospholipid translocases.

P.S. to PS (phosphatidylserine)--pertinent proteins in apoptotic cell clearance.

The psr protein has been proposed as the critical receptor that detects phosphatidylserine (PS) on the surface of apoptotic cells. However, for some time there has been evidence that this protein is not at the cell surface but in the nucleus. Now, the phenotype of a knockout of the Drosophila psr protein (dPSR) has discredited the identification altogether, lending impetus both to uncovering the real function of the protein and to identifying the real PS receptor. Interpretations of studies of two other genes supposedly involved in PS transport may be built on similarly shaky foundations.

Reliability and construct validity of the Automated Neuropsychological Assessment Metrics (ANAM) mood scale.

The reliability and construct validity of the Automated Neuropsychological Assessment Metrics (ANAM) mood scale (AMS) were examined using concurrent, well-validated measures of mood and confirmatory factor analysis (CFA) with a sample of 210 volunteer college students. The AMS was given in computerized format with multiple adjectives using a visual analog Likert scale yielding seven dimensions of mood including vigor, restlessness, depression, anger, fatigue, anxiety, and happiness. All seven mood dimensions of the AMS demonstrated excellent test-retest reliability and internal consistency. Also, the AMS anxiety dimension correlated strongly with the Spielberger's State Anxiety Inventory (r=0.67) and the AMS depression dimension correlated strongly with the Beck Depression Inventory-II (r=0.71). CFA revealed that the AMS 7-factor mood model fit the data well and significantly better than an alternative, theoretically plausible model. When concurrent measures of mood were incorporated in the CFA model, the AMS demonstrated both convergent and discriminant validity. The AMS 7-factor model explained 55.12% of the total variance in the items. It was concluded that the AMS provides a brief yet reasonably complete and valid assessment of mood.

Reference data from the automated Neuropsychological Assessment Metrics for use in traumatic brain injury in an active duty military sample.

The current study examined the performance of active duty soldiers on the Automated Neuropsychological Assessment Metrics (ANAM) traumatic brain injury test battery, to expand the reference data for use in military settings. The effects of age and gender on cognitive performance also were explored. The ANAM traumatic brain injury battery, consisting of six performance tests and two subjective scales, was administered to a sample of healthy active duty soldiers (N = 5,247) as part of a concussion surveillance program. Performance means and SDs, stratified according to age and gender, are reported as reference data. In addition, the impact of age and gender on performance measures was analyzed. Because ANAM is rapidly being adopted for use in many military medical and research applications, the establishment of these reference values is invaluable, particularly for assisting with rapid accurate evaluation and treatment in clinical settings.

Cognate putative nuclear localization signal effects strong nuclear localization of a GFP reporter and facilitates gene expression studies in Caenorhabditis elegans.

Targeting a gene expression reporter, usually the green fluorescent protein (GFP), to the nucleus via a translationally fused nuclear localization signal (NLS) greatly facilitates recognition and identification of the reporter-expressing cells in Caenorhabditis elegans. Presently circulating nematode transcriptional gene expression vectors use the viral NLS from simian virus 40 (SV40) large T antigen. This NLS, however fails to ensure sufficient localization of the GFP peptide to the nucleus. We modified the common transcriptional reporter SV40 NLS-GFP by adding to its C terminus a cognate putative NLS from the transcription factor egl-13. The EGL-13 NLS effected clear contrast in fluorescence intensity between the nucleus and the cytoplasm in cells with strong reporter signal and efficiently highlighted the nucleus in tissues with weak reporter expression in a wide range of tested tissues. The SV40 NLS-GFP-EGL-13 NLS vector should become a valuable tool for gene expression studies in C. elegans.

Signal transduction induced by apoptotic cells inhibits HIV transcription in monocytes/macrophages.

The primary targets of HIV are CD4(+) T cells and macrophages. HIV infection is associated with an increase in apoptosis of infected and uninfected CD4(+) T cells, and these infected cells undergo apoptosis and produce HIV virions with phosphatidylserine (PS) on their surface. During phagocytosis of apoptotic cells, macrophages, using an array of receptors, are able to perceive various surface changes on apoptotic cells. The engagement of phagocytic receptors by ligands on the apoptotic cell surface results in the activation of signaling cascades, which facilitate engulfment. In this study, we examined how PS associated with virions and apoptotic cells influences HIV replication. We demonstrate that virus-associated PS is required for HIV infection of macrophages at a step prior to integration but following strong-stop, indicating that PS-initiated signals alter the establishment of HIV provirus. Conversely, apoptotic cells inhibited HIV transcription in infected macrophages, although this ability to suppress transcription was independent of PS. Furthermore, we show that ELMO, a key signaling molecule that participates in the phagocytosis of apoptotic cells, inhibited HIV transcription; however, knocking down endogenous ELMO expression in infected U937 cells rescued HIV transcription when these cells were coincubated with apoptotic targets. Taken together, these data show that apoptotic cells and the signals, which they initiate upon recognition by macrophages, influence the successful establishment of HIV infection and provirus transcription.

Development and quality assurance of computer-based assessment batteries.

The purpose of this article is to outline critical elements in the development and quality assurance (QA) assessment of a computer-based assessment battery (CAB). The first section of the article provides an overview of the life cycle of a representative CAB, typical evolutionary stages, and many of the essential considerations for designing and developing a CAB. The second section of the article presents a model for conducting a quality assurance assessment of a CAB. A general narrative of several steps in the QA process is supported by a table of recommended QA assessment elements. Although this QA process model may not be definitive for all cases, it provides a general framework within which a systematic assessment of any CAB can be conducted.