At what scale should we assess the health of pelagic habitats? Trade-offs between small-scale manageable pressures and the need for regional upscaling

Major planktonic lifeforms such as diatoms, dinoflagellates, meroplankton and holoplankton have recently shown significant and alarming changes in abundance - mainly downwards trends - around the northwest European shelf. This has major implications for food web connections and for ecosystem services including seafood provision and carbon storage. We have quantified these changes in abundance for 2006–2019/20 using a Plankton Index (PI) and show that the scale of spatial aggregation is critical to the ability of the PI to detect change, understand causal mechanisms, and provide advice to policymakers. We derived PI statistics in the Celtic and North Seas from data from the Continuous Plankton Recorder survey offshore and England’s Environment Agency inshore using three sets of spatial units: (i) Ecohydrodynamic (EHD) units based on hydro-biogeochemical modelling, (ii) ‘COMP4′ areas based on cluster analysis of satellite data for chlorophyll a and primary productivity, and (iii) English coastal and estuarine Water Framework Directive (WFD) waterbodies. For the largest scale areas, the EHD units (median size 87,000 km2), we find greater change in plankton communities than previously reported, suggesting that these shifts have continued and possibly intensified in recent years. The smaller-scale COMP4 areas (median size 6,700 km2) appear to encompass more spatially coherent changes in plankton community structure than EHD units; at this scale PI values indicate community shifts of greater magnitude. These COMP4 areas provide a reasonable compromise scale for linking offshore plankton communities to large-scale drivers of change such as climate warming. For inshore plankton communities, larger changes are detected at the smaller WFD waterbody scale (median size 11 km2). This scale allows direct links to coastal management measures and is more suitable for linking to land-sourced pressures. Recent integration of the UK’s OSPAR and WFD plankton monitoring data management enables the exploration of changes across spatial scales to develop a holistic understanding of ecosystem health. Regional-sea scale derivation of the PI for coastal waters provides a clear indication that changes are occurring, at least in phytoplankton communities, while localised PI statistics offer an additional layer of information which can be an important tool for linking to localised drivers of change including coastal anthropogenic pressures. Broadscale inshore zooplankton monitoring is needed to evaluate the coastal plankton community holistically; zooplankton communities offshore are also changing but these changes cannot currently be linked to coastal processes. Layering information across spatial scales provides a breadth of system-level understanding beyond what any one typology can provide

Outline of a Genome Navigation System Based on the Properties of GA-Sequences and Their Flanks

Introducing a new method to visualize large stretches of genomic DNA (see Appendix S1) the article reports that most GA-sequences [1] shared chains of tetra-GA-motifs and contained upstream poly(A)-segments. Although not integral parts of them, Alu-elements were found immediately upstream of all human and chimpanzee GA-sequences with an upstream poly(A)-segment. The article hypothesizes that genome navigation uses these properties of GA-sequences in the following way. (1) Poly(A) binding proteins interact with the upstream poly(A)-segments and arrange adjacent GA-sequences side-by-side (‘GA-ribbon’), while folding the intervening DNA sequences between them into loops (‘associated DNA-loops’). (2) Genome navigation uses the GA-ribbon as a search path for specific target genes that is up to 730-fold shorter than the full-length chromosome. (3) As to the specificity of the search, each molecule of a target protein is assumed to catalyze the formation of specific oligomers from a set of transcription factors that recognize tetra-GA-motifs. Their specific combinations of tetra-GA motifs are assumed to be present in the particular GA-sequence whose associated loop contains the gene for the target protein. As long as the target protein is abundant in the cell it produces sufficient numbers of such oligomers which bind to their specific GA-sequences and, thereby, inhibit locally the transcription of the target protein in the associated loop. However, if the amount of target protein drops below a certain threshold, the resultant reduction of specific oligomers leaves the corresponding GA-sequence ‘denuded’. In response, the associated DNA-loop releases its nucleosomes and allows transcription of the target protein to proceed. (4) The Alu-transcripts may help control the general background of protein synthesis proportional to the number of transcriptionally active associated loops, especially in stressed cells. (5) The model offers a new mechanism of co-regulation of protein synthesis based on the shared segments of different GA-sequences

Modulation of Cytochrome P450 Metabolism and Transport across Intestinal Epithelial Barrier by Ginger Biophenolics

Natural and complementary therapies in conjunction with mainstream cancer care are steadily gaining popularity. Ginger extract (GE) confers significant health-promoting benefits owing to complex additive and/or synergistic interactions between its bioactive constituents. Recently, we showed that preservation of natural ‘‘milieu’’ confers superior anticancer activity on GE over its constituent phytochemicals, 6-gingerol (6G), 8-gingerol (8G), 10-gingerol (10G) and 6-shogaol (6S), through enterohepatic recirculation. Here we further evaluate and compare the effects of GE and its major bioactive constituents on cytochrome P450 (CYP) enzyme activity in human liver microsomes by monitoring metabolites of CYPspecific substrates using LC/MS/MS detection methods. Our data demonstrate that individual gingerols are potent inhibitors of CYP isozymes, whereas GE exhibits a much higher half-maximal inhibition value, indicating no possible herb-drug interactions. However, GE’s inhibition of CYP1A2 and CYP2C8 reflects additive interactions among the constituents. In addition, studies performed to evaluate transporter-mediated intestinal efflux using Caco-2 cells revealed that GE and its phenolics are not substrates of P-glycoprotein (Pgp). Intriguingly, however, 10G and 6S were not detected in the receiver compartment, indicating possible biotransformation across the Caco-2 monolayer. These data strengthen the notion that an interplay of complex interactions among ginger phytochemicals when fed as whole extract dictates its bioactivity highlighting the importance of consuming whole foods over single agents. Our study substantiates the need for an indepth analysis of hepatic biotransformation events and distribution profiles of GE and its active phenolics for the design of safe regimens

At what scale should we assess the health of pelagic habitats? Trade-offs between small-scale manageable pressures and the need for regional upscaling

Major planktonic lifeforms such as diatoms, dinoflagellates, meroplankton and holoplankton have recently shown significant and alarming changes in abundance - mainly downwards trends - around the northwest European shelf. This has major implications for food web connections and for ecosystem services including seafood provision and carbon storage. We have quantified these changes in abundance for 2006–2019/20 using a Plankton Index (PI) and show that the scale of spatial aggregation is critical to the ability of the PI to detect change, understand causal mechanisms, and provide advice to policymakers.We derived PI statistics in the Celtic and North Seas from data from the Continuous Plankton Recorder survey offshore and England’s Environment Agency inshore using three sets of spatial units: (i) Ecohydrodynamic (EHD) units based on hydro-biogeochemical modelling, (ii) ‘COMP4′ areas based on cluster analysis of satellite data for chlorophyll a and primary productivity, and (iii) English coastal and estuarine Water Framework Directive (WFD) waterbodies. For the largest scale areas, the EHD units (median size 87,000 km2), we find greater change in plankton communities than previously reported, suggesting that these shifts have continued and possibly intensified in recent years. The smaller-scale COMP4 areas (median size 6,700 km2) appear to encompass more spatially coherent changes in plankton community structure than EHD units; at this scale PI values indicate community shifts of greater magnitude. These COMP4 areas provide a reasonable compromise scale for linking offshore plankton communities to large-scale drivers of change such as climate warming. For inshore plankton communities, larger changes are detected at the smaller WFD waterbody scale (median size 11 km2). This scale allows direct links to coastal management measures and is more suitable for linking to land-sourced pressures.Recent integration of the UK’s OSPAR and WFD plankton monitoring data management enables the exploration of changes across spatial scales to develop a holistic understanding of ecosystem health. Regional-sea scale derivation of the PI for coastal waters provides a clear indication that changes are occurring, at least in phytoplankton communities, while localised PI statistics offer an additional layer of information which can be an important tool for linking to localised drivers of change including coastal anthropogenic pressures. Broadscale inshore zooplankton monitoring is needed to evaluate the coastal plankton community holistically; zooplankton communities offshore are also changing but these changes cannot currently be linked to coastal processes. Layering information across spatial scales provides a breadth of system-level understanding beyond what any one typology can provide

Fast-TIPL Occurs for Salient Images without a Memorization Requirement in Men but Not in Women

Recent research of task-irrelevant perceptual learning (TIPL) demonstrates that stimuli that are consistently presented at relevant point in times (e.g. with task-targets or rewards) are learned, even in the absence of attention to these stimuli. However, different research paradigms have observed different results for how salient stimuli are learned; with some studies showing no learning, some studies showing positive learning and others showing negative learning effects. In this paper we focused on how the level of processing of stimuli impacts fast-TIPL. We conducted three different experiments in which the level of processing of the information paired with a target was manipulated. Our results indicated that fast-TIPL occurs when participants have to memorize the information presented with the target, but also when they just have to process this information for a secondary task without an explicit memorization of those stimuli. However, fast-TIPL does not occur when participants have to ignore the target-paired information. This observation is consistent with recent models of TIPL that suggest that attentional signals can either enhance or suppress learning depending on whether those stimuli are distracting or not to the subjects' objectives. Our results also revealed a robust gender effect in fast-TIPL, where male subjects consistently show fast-TIPL, whereas the observation of fast-TIPL is inconsistent in female subjects

The Effect of Performance-Based Financial Incentives on Improving Patient Care Experiences: A Statewide Evaluation

Patient experience measures are central to many pay-for-performance (P4P) programs nationally, but the effect of performance-based financial incentives on improving patient care experiences has not been assessed. The study uses Clinician & Group CAHPS data from commercially insured adult patients (n = 124,021) who had visits with 1,444 primary care physicians from 25 California medical groups between 2003 and 2006. Medical directors were interviewed to assess the magnitude and nature of financial incentives directed at individual physicians and the patient experience improvement activities adopted by groups. Multilevel regression models were used to assess the relationship between performance change on patient care experience measures and medical group characteristics, financial incentives, and performance improvement activities. Over the course of the study period, physicians improved performance on the physician-patient communication (0.62 point annual increase, p < 0.001), care coordination (0.48 point annual increase, p < 0.001), and office staff interaction (0.22 point annual increase, p = 0.02) measures. Physicians with lower baseline performance on patient experience measures experienced larger improvements (p < 0.001). Greater emphasis on clinical quality and patient experience criteria in individual physician incentive formulas was associated with larger improvements on the care coordination (p < 0.01) and office staff interaction (p < 0.01) measures. By contrast, greater emphasis on productivity and efficiency criteria was associated with declines in performance on the physician communication (p < 0.01) and office staff interaction (p < 0.001) composites. In the context of statewide measurement, reporting, and performance-based financial incentives, patient care experiences significantly improved. In order to promote patient-centered care in pay for performance and public reporting programs, the mechanisms by which program features influence performance improvement should be clarified

The regulatory role of long-term depression in juvenile and adult mouse ocular dominance plasticity

The study of experience-dependent ocular dominance (OD) plasticity has greatly contributed to the understanding of visual development. During the critical period, preventing input from one eye results in a significant impairment of vision, and loss of cortical responsivity via the deprived eye. Residual ocular dominance plasticity has recently been observed in adulthood. Accumulating evidence suggests that OD plasticity involves N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD). Here we report that the administration of a selective LTD antagonist prevented the ocular dominance shift during the critical period. The NMDAR co-agonist D-serine facilitated adult visual cortical LTD and the OD shift in short-term monocularly deprived (MD) adult mice. When combined with reverse suture, D-serine proved effective in restoring a contralaterally-dominated visual input pattern in long-term MD mice. This work suggests LTD as a key mechanism in both juvenile and adult ocular dominance plasticity, and D-serine as a potential therapeutic in human amblyopic subjects

Circadian Rhythm-Dependent Alterations of Gene Expression in Drosophila Brain Lacking Fragile X Mental Retardation Protein

Fragile X syndrome is caused by the loss of the FMR1 gene product, fragile X mental retardation protein (FMRP). The loss of FMRP leads to altered circadian rhythm behaviors in both mouse and Drosophila; however, the molecular mechanism behind this phenomenon remains elusive. Here we performed a series of gene expression analyses, including of both mRNAs and microRNAs (miRNAs), and identified a number of mRNAs and miRNAs (miRNA-1 and miRNA-281) with circadian rhythm-dependent altered expression in dfmr1 mutant flies. Identification of these RNAs lays the foundation for future investigations of the molecular pathway(s) underlying the altered circadian rhythms associated with loss of dFmr1

Modelling stereotyping in cooperation systems

Cooperation is a sophisticated example of collective intelligence. This is particularly the case for indirect reciprocity, where benefit is provided to others without a guarantee of a future return. This is becoming increasingly relevant to future technology, where autonomous machines face cooperative dilemmas. This paper addresses the problem of stereotyping, where traits belonging to an individual are used as proxy when assessing their reputation. This is a cognitive heuristic that humans frequently use to avoid deliberation, but can lead to negative societal implications such as discrimination. It is feasible that machines could be equally susceptible. Our contribution concerns a new and general framework to examine how stereotyping affects the reputation of agents engaging in indirect reciprocity. The framework is flexible and focuses on how reputations are shared. This offers the opportunity to assess the interplay between the sharing of traits and the cost, in terms of reduced cooperation, through opportunities for shirkers to benefit. This is demonstrated using a number of key scenarios. In particular, the results show that cooperation is sensitive to the structure of reputation sharing between individuals