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The segmentally duplicated Pregnancy-specific glycoprotein (PSG) locus on chromosome 19q13 may be one of the most rapidly evolving in the human genome. It comprises ten coding genes (PSG1-9, 11) and one predominantly non-coding gene (PSG10) that are expressed in the placenta and gut, in addition to several poorly characterized long non-coding RNAs. We report that long non-coding RNA PSG8-AS1 has an oligodendrocyte-specific expression pattern and is co-expressed with genes encoding key myelin constituents. PSG8-AS1 exhibits two peaks of expression during human brain development coinciding with the most active periods of oligodendrogenesis and myelination. PSG8-AS1 orthologs were found in the genomes of several primates but significant expression was found only in the human, suggesting a recent evolutionary origin of its proposed role in myelination. Additionally, because co-deletion of chromosomes 1p/19q is a genomic marker of oligodendroglioma, expression of PSG8-AS1 was examined in these tumors. PSG8-AS1 may be a promising diagnostic biomarker for glioma, with prognostic value in oligodendroglioma.

Restoration supports the recovery of ecological attributes such as cover, complexity, and diversity to slow the areal decline of natural ecosystems. Restoration activity is intensifying worldwide to combat persistent stressors that are driving global declines to the extent and resilience of coral reefs. However, restoration is disputed as a meaningful aid to reef ecological recovery, often as an expensive distraction to addressing the root causes of reef loss. We contend this dispute partly stems from inferences drawn from small-scale experimental restoration outcomes amplified by misconceptions around cost-based reasoning. Alongside aggressive emissions reductions, we advocate urgent investment in coral reef ecosystem restoration as part of the management toolbox to combat the destruction of reefs as we know them within decades.

Background: The well-characterised role of the immune system in acute ischaemic stroke has prompted the search for immunomodulatory therapies. Pregnancy-specific glycoproteins (PSGs) are a group of proteins synthesised by placental trophoblasts which show immunomodulatory properties. The aim of this study was to determine whether a proposed PSG1-based therapeutic enhanced recovery in a mouse model of brain ischaemia and to explore possible immunomodulatory effects. Methods: Mice underwent permanent electrocoagulation of the left middle cerebral artery (pMCAO). They received saline (n = 20) or recombinant pregnancy-specific glycoprotein-1-alpha “fused” to the Fc domain of IgG1 (rPSG1-Fc) (100 μg) (n = 22) at 1 h post-ischaemia. At 3 and 5 days post-ischaemia, neurobehavioural recovery was assessed by the grid-walking test. At 5 days post-ischaemia, lesion size was determined by NeuN staining. Peripheral T cell populations were quantified via flow cytometry. Immunohistochemistry was used to quantify ICAM-1 expression and FoxP3+ cell infiltration in the ischaemic brain. Immunofluorescence was employed to determine microglial activation status via Iba-1 staining.Results: rPSG1-Fc significantly enhanced performance in the grid-walking test at 3 and 5 days post-ischaemia. No effect on infarct size was observed. A significant increase in circulating CD4+ FoxP3+ cells and brain-infiltrating FoxP3+ cells was noted in rPSG1-Fc-treated mice. Among CD4+ cells, rPSG1-Fc enhanced the expression of IL-10 in spleen, blood, draining lymph nodes, and non-draining lymph nodes, while downregulating IFN-γ and IL-17 in spleen and blood. A similar cytokine expression pattern was observed in CD8+ cells. rPSG1-Fc reduced activated microglia in the infarct core. Conclusion: The administration of rPSG1-Fc improved functional recovery in post-ischaemic mice without impacting infarct size. Improved outcome was associated with a modulation of the cytokine-secreting phenotype of CD4+ and CD8+ T cells towards a more regulatory phenotype, as well as reduced activation of microglia. This establishes proof-of-concept of rPSG1-Fc as a potential stroke immunotherapy.

Making high quality but affordable Pinot noir (PN) wine is challenging in most terroirs and New Zealand (NZ)’s situation is no exception. To increase the probability of making highly typical PN wines, producers choose to grow grapes in cool climates on lower fertility soils while adopting labour intensive practices. Stringent yield targets and higher input costs necessarily mean that PN wine cost is high, and profitability lower, in affordable varietal wine ranges. To understand if higher-yielding vines produce wines of lower quality we have undertaken an extensive study of PN in NZ. Since 2018, we established a network of twelve trial sites in three NZ regions to find individual vines that produced acceptable commercial yields (above 2.0 kg per metre of row) and wines of composition comparable to “Icon” labels. Approximately 20 % of 660 grape lots (N = 135) were selected within a narrow juice Total Soluble Solids (TSS) range of 22.0 ± 1.0 °Brix and made into single-vine wines under controlled conditions. Multiple Factor Analysis of the vine, berry, juice and wine parameters from three vintages found grape Berry Weight to be the most effective clustering variable. As the Berry Weight category decreased, there was a systematic increase in the probability of higher berry red colour and total phenolics with a parallel increase in wine phenolics and decreased juice amino acids. The influence of berry weight on wine composition would appear stronger than the individual effects of Vintage, Region, Vineyard or vine Yield. Our observations support the hypothesis that it is possible to produce PN wines that fall within an “Icon” benchmark composition range at yields above 2.5 kg per vine, provided that the Leaf Area:Fruit Weight ratio is above 11 cm2 per g, mean berry weight is below 1.2 g and juice TSS is above 22 °Brix.

There is interest in linking outputs from land use simulators to bird species distribution models to project how boreal birds will respond to cumulative effects of caribou (Rangifer tarandus) conservation, harvest, fire, and energy-sector development in Alberta. Our hypotheses were: (1) species associated with older mixed-wood stands would decline more if harvest was shifted away from areas used by caribou to areas with more mixed-wood; and (2) species associated with older forests would be more negatively affected by the combined effects of harvest, fire, and non-forestry footprint than by harvest alone. We used vegetation data from two harvest scenarios produced in Patchworks as inputs for density models of 20 boreal forest songbird and woodpecker species in Alberta. We projected abundance of these species over 50 years under: 1) two scenarios created in Patchworks, without fire but with and without deferral of timber harvest within a caribou conservation zone on lands tenured to Alberta-Pacific Forest Industries Inc.; (2) a scenario with fire but no human footprint; and (3) five scenarios in ALCES Online, in which habitat was affected by Patchworks harvest locations, fire (1–2 × current rate), and energy sector development (present or absent; with or without seismic line reclamation to improve caribou habitat). In the Patchworks scenarios, we found similar projected numbers of each bird species over time, whether harvest deferral occurred or not. Both harvest plans increased habitat and numbers for most species associated with older forests over 50 years, while most species associated with younger forests declined in both harvest plans, because average projected forest age increased over 50 years. Fire and other footprint generally reduced relative amount of habitat for species associated with older forests, which still increased over time, while other species responded positively or less negatively to fire. Seismic restoration created habitat for three-quarters of species that responded negatively to energy sector development over 50 years. As projections depended on whether just harvest, fire or all footprints were analyzed, multiple human impacts over time beyond harvest should be considered in conservation and land use planning based on long-term predictions about wildlife in anthropogenic landscapes.

Abstract Background Ex-vivo normothermic perfusion strategies are a promising new instrument in organ transplantation. The perfusion conditions are designed to be protective however the artificial environment can induce a local inflammatory response. The aim of this study was to determine the effect of incorporating a Cytosorb adsorber into an isolated kidney perfusion system. Methods Porcine kidneys were subjected to 22 h of cold ischaemia then reperfused for 6 h on an ex vivo reperfusion circuit. Pairs of kidneys were randomised to either control (n = 5) or reperfusion with a Cytosorb adsorber (n = 5) integrated into the circuit. Tissue, blood and urine samples were taken for the measurement of inflammation and renal function. Results Baseline levels of cytokines (IL-6, TNFα, IL-8, IL-10, IL-1β, IL-1α) were similar between groups. Levels of IL-6 and IL-8 in the perfusate significantly increased during reperfusion in the control group but not in the Cytosorb group (P = 0.023, 0.049). Levels of the other cytokines were numerically lower in the Cytosorb group; however, this did not reach statistical significance. The mean renal blood flow (RBF) was significantly higher in the Cytosorb group (162 ± 53 vs. 120 ± 35 mL/min/100 g; P = 0.022). Perfusate levels of prostaglandin E2 were significantly lower in the Cytosorb group (642 ± 762 vs. 3258 ± 980 pg/mL; P = 0.0001). Levels of prostacyclin were significantly lower in the Cytosorb group at 1, 3 and 6 h of reperfusion (P = 0.008, 0.003, 0.0002). Levels of thromboxane were also significantly lower in the Cytosorb group throughout reperfusion (P = 0.005). Haemoadsorption had no effect on creatinine clearance (P = 0.109). Conclusion Haemoadsorption can reduce the inflammatory response and improve renal blood flow during perfusion. Nonetheless, in this model haemoadsorption had no influence on renal function and this may relate to the broad-spectrum action of the Cytosorb adsorber that also removes potentially important anti-inflammatory mediators.

Autism is a genetically complex neurobehavioral disorder with a population prevalence of more than 1%. Cerebellar abnormalities, including Purkinje cell deficits in the vermis, are consistently reported, and rodent models of cerebellar dysfunction exhibit features analogous to human autism. We previously analyzed the regulation and expression of the pseudoautosomal region 2 gene SPRY3, which is adjacent to X chromosome-linked TMLHE, a known autism susceptibility gene. SPRY3 is a regulator of branching morphogenesis and is strongly expressed in Purkinje cells. We previously showed that mouse Spry3 is not expressed in cerebellar vermis lobules VI–VII and X, regions which exhibit significant Purkinje cell loss or abnormalities in autism. However, these lobules have relatively high expression of p75NTR, which encodes a neurotrophin receptor implicated in autism. We propose a mechanism whereby inappropriate SPRY3 expression in these lobules could interact with TrkB and p75NTR signaling pathways resulting in Purkinje cell pathology. We report preliminary characterization of X and Y chromosome-linked regulatory sequences upstream of SPRY3, which are polymorphic in the general population. We suggest that an OREG-annotated region on chromosome Yq12 ∼60 kb from SPRY3 acts as a silencer of Y-linked SPRY3 expression. Deletion of a β-satellite repeat, or alterations in chromatin structure in this region due to trans-acting factors, could affect the proposed silencing function, leading to reactivation and inappropriate expression of Y-linked SPRY3. This proposed male-specific mechanism could contribute to the male bias in autism prevalence.

Ozone (O3) is a key air pollutant that is produced from precursor emissions and has adverse impacts on human health and ecosystems. In the U.S., the Clean Air Act (CAA) regulates O3 levels to protect public health and welfare, but unraveling the origins of surface O3 is complicated by the presence of contributions from multiple sources including background sources like stratospheric transport, wildfires, biogenic precursors, and international anthropogenic pollution, in addition to U.S. anthropogenic sources. In this report, we consider more than 100 published studies and assess current knowledge on the spatial and temporal distribution, trends, and sources of background O3 over the continental U.S., and evaluate how it influences attainment of the air quality standards. We conclude that spring and summer seasonal mean U.S. background O3 (USB O3), or O3 formed from natural sources plus anthropogenic sources in countries outside the U.S., is greatest at high elevation locations in the western U.S., with monthly mean maximum daily 8-hour average (MDA8) mole fractions approaching 50 parts per billion (ppb) and annual 4th highest MDA8s exceeding 60 ppb, at some locations. At lower elevation sites, e.g., along the West and East Coasts, seasonal mean MDA8 USB O3 is in the range of 20–40 ppb, with generally smaller contributions on the highest O3 days. The uncertainty in U.S. background O3 is around ±10 ppb for seasonal mean values and higher for individual days. Noncontrollable O3 sources, such as stratospheric intrusions or precursors from wildfires, can make significant contributions to O3 on some days, but it is challenging to quantify accurately these contributions. We recommend enhanced routine observations, focused field studies, process-oriented modeling studies, and greater emphasis on the complex photochemistry in smoke plumes as key steps to reduce the uncertainty associated with background O3 in the U.S.

The federal channel at Port of Miami, Florida, USA, was dredged between late 2013 and early 2015 to widen and deepen the channel. Due to the limited spatial extent of impact-assessment monitoring associated with the project, the extent of the dredging impacts on surrounding coral reefs has not been well quantified. Previously published remote sensing analyses, as well as agency and anecdotal reports suggest the most severe and largest area of sedimentation occurred on a coral reef feature referred to as the Inner Reef, particularly in the sector north of the channel. A confounding regional warm-water mass bleaching event followed by a coral disease outbreak during this same time frame made the assessment of dredging-related impacts to coral reefs adjacent to the federal channel difficult but still feasible. The current study sought to better understand the sedimentation impacts that occurred in the coral reef environment surrounding Port of Miami, to distinguish those impacts from other regional events or disturbances, and provide supplemental information on impact assessment that will inform discussions on compensatory mitigation requirements. To this end, in-water field assessments conducted after the completion of dredging and a time series analysis of tagged corals photographed pre-, during, and post-dredging, are used to discern dredging-related sedimentation impacts for the Inner Reef north. Results indicate increased sediment accumulation, severe in certain times and places, and an associated biological response (e.g., higher prevalence of partial mortality of corals) extended up to 700 m from the channel, whereas project-associated monitoring was limited to 50 m from the channel. These results can contribute to more realistic prediction of areas of indirect effect from dredging projects needed to accurately evaluate proposed projects and design appropriate compliance monitoring. Dredging projects near valuable and sensitive habitats subject to local and global stressors require monitoring methods capable of discerning non-dredging related impacts and adaptive management to ensure predicted and unpredicted project-related impacts are quantified. Anticipated increasing frequency and intensity of seasonal warming stress also suggests that manageable- but- unavoidable local stressors such as dredging should be partitioned from such seasonal thermal stress events.

Pregnancy-specific glycoproteins (PSGs) are immunoglobulin superfamily members encoded by multigene families in rodents and primates. In human pregnancy, PSGs are secreted by the syncytiotrophoblast, a fetal tissue, and reach a concentration of up to 400 ug/ml in the maternal bloodstream at term. Human and mouse PSGs induce release of anti-inflammatory cytokines such as IL-10 and TGFβ1 from monocytes, macrophages, and other cell types, suggesting an immunoregulatory function. RGD tri-peptide motifs in the majority of human PSGs suggest that they may function like snake venom disintegrins, which bind integrins and inhibit interactions with ligands. We noted that human PSG1 has a KGD, rather than an RGD motif. The presence of a KGD in barbourin, a platelet integrin αIIbβ3 antagonist found in snake venom, suggested that PSG1 may be a selective αIIbβ3 ligand. Here we show that human PSG1 binds αIIbβ3 and inhibits the platelet - fibrinogen interaction. Unexpectedly, however, the KGD is not critical as multiple PSG1 domains independently bind and inhibit αIIbβ3 function. Human PSG9 and mouse Psg23 are also inhibitory suggesting conservation of this function across primate and rodent PSG families. Our results suggest that in species with haemochorial placentation, in which maternal blood is in direct contact with fetal trophoblast, the high expression level of PSGs reflects a requirement to antagonise abundant (3 mg/ml) fibrinogen in the maternal circulation, which may be necessary to prevent platelet aggregation and thrombosis in the prothrombotic maternal environment of pregnancy.

This article presents the results of a pilot programme of fieldwork carried out between 2000-3 in the Arroux Valley in southern Burgundy close to Autun and Mont Beuvray. In the late Iron Age, this region was inhabited by the Aedui, an early ally of Rome, who had their principal stronghold at Mont Beuvray (Bibracte), high up in the Morvan. The 19th century excavations established this oppidum as a type-site for the European Iron Age, and since 1984 it has been the focus of an international research programme, which has greatly enhanced our knowledge of the site. In the Augustan period, Mont Beuvray was however replaced by Autun (Augustodunum) on the banks of the Arroux as the new civitas capital. It rapidly developed into one of the major cities of Roman Gaul and like Mont Beuvray has been the subject of extensive excavations. Composite image of the survey There has been far less research on rural settlement in the region. This lack of investigation has much to do with present-day land use. The Morvan used to be extensively cultivated, but nowadays is mainly pasture or woodland, severely limiting the possibilities for either aerial reconnaissance or conventional fieldwalking. Next to nothing is known about the Iron Age settlement pattern around Mont Beuvray and Gallo-Roman settlement around Autun is only slightly better attested. It would be surprising however if the hinterland of both sites was not densely settled through this period, particularly the lower-lying ground of the Arroux valley itself. The fieldwork programme reported here was designed to test the possibility of using a combination of extensive geophysical survey and linewalking the few arable fields that exist to characterise rural settlement in the environs of these two major centres. Three micro-areas in the Arroux valley between Autun and Etang, and that of its tributary, the Celle, were selected for more detailed investigation, two of them in the commune of Monthelon, the third in Laizy. In all, a total area of 132 ha was prospected between 2000-2003 in the three micro-zones, representing just under 10% of their total areas, but nearer 15% of the area available for survey. About 80 ha (60%) was examined by fieldwalking, 62 ha (47%) by gradiometry and 11 ha (8%) by resistivity, together leading to the discovery of numerous hitherto unknown sites and scatters spanning the period from the Neolithic to the early Middle Ages, as well as enabling the better characterisation of other sites known from earlier chance discoveries. The results are presented in detail followed by an overview of the Iron Age and Gallo-Roman pottery collected at the different locations, for which a type series has been built up and linked where possible to the local reference collections from Mont Beuvray and Autun. In the concluding section, the extent to which the results have been able to throw new light on the principal research questions posed at the outset of the project are assessed. These were as follows: (1) what was the nature of Iron Age settlement in the area prior to the foundation of Mont Beuvray? (2) is there any evidence of a reduction in the number of later Iron Age rural sites at the period when the oppidum was occupied, as happens in regions such as the Auvergne and Picardy? (3) how does Gallo-Roman settlement vary through time or with distance from Autun? (4) do rural site numbers and/or visibility in the early and later Empire follow similar trends to other parts of the Roman west? (5) is there any evidence for precocious Roman cultural expression at rural sites in the region similar to that seen on Mont Beuvray itself? As a result of this work, a series of preliminary suggestions can now be offered, although to answer all the questions in full would require a far more extensive programme of survey.

Changes in mature forest cover amount, composition, and configuration can be of significant consequence to wildlife populations. The response of wildlife to forest patterns is of concern to forest managers because it lies at the heart of such competing approaches to forest planning as aggregated vs. dispersed harvest block layouts. In this study, we developed a species assessment framework to evaluate the outcomes of forest management scenarios on biodiversity conservation objectives. Scenarios were assessed in the context of a broad range of forest structures and patterns that would be expected to occur under natural disturbance and succession processes. Spatial habitat models were used to predict the effects of varying degrees of mature forest cover amount, composition, and configuration on habitat occupancy for a set of 13 focal songbird species. We used a spatially explicit harvest scheduling program to model forest management options and simulate future forest conditions resulting from alternative forest management scenarios, and used a process-based fire-simulation model to simulate future forest conditions resulting from natural wildfire disturbance. Spatial pattern signatures were derived for both habitat occupancy and forest conditions, and these were placed in the context of the simulated range of natural variation. Strategic policy analyses were set in the context of current Ontario forest management policies. This included use of sequential time-restricted harvest blocks (created for Woodland caribou (Rangifer tarandus) conservation) and delayed harvest areas (created for American marten (Martes americana atrata) conservation). This approach increased the realism of the analysis, but reduced the generality of interpretations. We found that forest management options that create linear strips of old forest deviate the most from simulated natural patterns, and had the greatest negative effects on habitat occupancy, whereas policy options that specify deferment and timing of harvest for large blocks helped ensure the stable presence of an intact mature forest matrix over time. The management scenario that focused on maintaining compositional targets best supported biodiversity objectives by providing the composition patterns required by the 13 focal species, but this scenario may be improved by adding some broad-scale spatial objectives to better maintain large blocks of interior forest habitat through time.