Chronic treatment with D2-antagonist haloperidol leads to inhibitory/excitatory imbalance in striatal D1-neurons.

Striatal dysfunction has been implicated in the pathophysiology of schizophrenia, a disorder characterized by positive symptoms such as hallucinations and delusions. Haloperidol is a typical antipsychotic medication used in the treatment of schizophrenia that is known to antagonize dopamine D2 receptors, which are abundantly expressed in the striatum. However, haloperidol's delayed therapeutic effect also suggests a mechanism of action that may go beyond the acute blocking of D2 receptors. Here, we performed proteomic analysis of striatum brain tissue and found more than 400 proteins significantly altered after 30 days of chronic haloperidol treatment in mice, namely proteins involved in glutamatergic and GABAergic synaptic transmission. Cell-type specific electrophysiological recordings further revealed that haloperidol not only reduces the excitability of striatal medium spiny neurons expressing dopamine D2 receptors (D2-MSNs) but also affects D1-MSNs by increasing the ratio of inhibitory/excitatory synaptic transmission (I/E ratio) specifically onto D1-MSNs but not D2-MSNs. Therefore, we propose the slow remodeling of D1-MSNs as a mechanism mediating the delayed therapeutic effect of haloperidol over striatum circuits. Understanding how haloperidol exactly contributes to treating schizophrenia symptoms may help to improve therapeutic outcomes and elucidate the molecular underpinnings of this disorder.

The effect of climate change on avian offspring production: A global meta-analysis.

Climate change affects timing of reproduction in many bird species, but few studies have investigated its influence on annual reproductive output. Here, we assess changes in the annual production of young by female breeders in 201 populations of 104 bird species (N = 745,962 clutches) covering all continents between 1970 and 2019. Overall, average offspring production has declined in recent decades, but considerable differences were found among species and populations. A total of 56.7% of populations showed a declining trend in offspring production (significant in 17.4%), whereas 43.3% exhibited an increase (significant in 10.4%). The results show that climatic changes affect offspring production through compounded effects on ecological and life history traits of species. Migratory and larger-bodied species experienced reduced offspring production with increasing temperatures during the chick-rearing period, whereas smaller-bodied, sedentary species tended to produce more offspring. Likewise, multi-brooded species showed increased breeding success with increasing temperatures, whereas rising temperatures were unrelated to reproductive success in single-brooded species. Our study suggests that rapid declines in size of bird populations reported by many studies from different parts of the world are driven only to a small degree by changes in the production of young.

Thirty years of marine debris in the Southern Ocean: Annual surveys of two island shores in the Scotia Sea.

We report on three decades of repeat surveys of beached marine debris at two locations in the Scotia Sea, in the Southwest Atlantic sector of the Southern Ocean. Between October 1989 and March 2019 10,112 items of beached debris were recovered from Main Bay, Bird Island, South Georgia in the northern Scotia Sea. The total mass of items (data from 1996 onwards) was 101 kg. Plastic was the most commonly recovered item (97.5% by number; 89% by mass) with the remainder made up of fabric, glass, metal, paper and rubber. Mean mass per item was 0.01 kg and the rate of accumulation was 100 items km-1 month-1. Analyses showed an increase in the number of debris items recovered (5.7 per year) but a decline in mean mass per item, suggesting a trend towards more, smaller items of debris at Bird Island. At Signy Island, South Orkney Islands, located in the southern Scotia Sea and within the Antarctic Treaty area, debris items were collected from three beaches, during the austral summer only, between 1991 and 2019. In total 1304 items with a mass of 268 kg were recovered. Plastic items contributed 84% by number and 80% by mass, with the remainder made up of metal (6% by number; 14% by mass), rubber (4% by number; 3% by mass), fabric, glass and paper (<1% by number; 3% by mass). Mean mass per item was 0.2 kg and rate of accumulation was 3 items km-1 month-1. Accumulation rates were an order of magnitude higher on the western (windward) side of the island (13-17 items km-1 month-1) than the eastern side (1.5 items km-1 month-1). Analyses showed a slight decline in number and slight increase in mean mass of debris items over time at Signy Island. This study highlights the prevalence of anthropogenic marine debris (particularly plastic) in the Southern Ocean. It shows the importance of long-term monitoring efforts in attempting to catalogue marine debris and identify trends, and serves warning of the urgent need for a wider understanding of the extent of marine debris across the whole of the Southern Ocean.

Identification of marine Important Bird and Biodiversity Areas for penguins around the South Shetland Islands and South Orkney Islands.

AIM: To provide a method of analyzing penguin tracking data to identify priority at-sea areas for seabird conservation (marine IBAs), based on pre-existing approaches for flying seabirds but revised according to the specific ecology of Pygoscelis penguin species. LOCATION: Waters around the Antarctic Peninsula, South Shetland, and South Orkney archipelagos (FAO Subareas 48.1 and 48.2). METHODS: We made key improvements to the pre-existing protocol for identifying marine IBAs that include refining the track interpolation method and revision of parameters for the kernel analysis (smoothing factor and utilization distribution) using sensitivity tests. We applied the revised method to 24 datasets of tracking data on penguins (three species, seven colonies, and three different breeding stages-incubation, brood, and crèche). RESULTS: We identified five new marine IBAs for seabirds in the study area, estimated to hold ca. 600,000 adult penguins. MAIN CONCLUSIONS: The results demonstrate the efficacy of a new method for the designation of a network of marine IBAs in Antarctic waters for penguins based on tracking data, which can contribute to an evidence-based, precautionary, management framework for krill fisheries.

Comparative population genomics reveals key barriers to dispersal in Southern Ocean penguins.

The mechanisms that determine patterns of species dispersal are important factors in the production and maintenance of biodiversity. Understanding these mechanisms helps to forecast the responses of species to environmental change. Here, we used a comparative framework and genomewide data obtained through RAD-Seq to compare the patterns of connectivity among breeding colonies for five penguin species with shared ancestry, overlapping distributions and differing ecological niches, allowing an examination of the intrinsic and extrinsic barriers governing dispersal patterns. Our findings show that at-sea range and oceanography underlie patterns of dispersal in these penguins. The pelagic niche of emperor (Aptenodytes forsteri), king (A. patagonicus), Adélie (Pygoscelis adeliae) and chinstrap (P. antarctica) penguins facilitates gene flow over thousands of kilometres. In contrast, the coastal niche of gentoo penguins (P. papua) limits dispersal, resulting in population divergences. Oceanographic fronts also act as dispersal barriers to some extent. We recommend that forecasts of extinction risk incorporate dispersal and that management units are defined by at-sea range and oceanography in species lacking genetic data.

Population Size and Decadal Trends of Three Penguin Species Nesting at Signy Island, South Orkney Islands.

We report long-term changes in population size of three species of sympatrically breeding pygoscelid penguins: Adélie (Pygoscelis adeliae), chinstrap (Pygoscelis antarctica) and gentoo (Pygoscelis papua ellsworthii) over a 38 year period at Signy Island, South Orkney Islands, based on annual counts from selected colonies and decadal all-island systematic counts of occupied nests. Comparing total numbers of breeding pairs over the whole island from 1978/79 to 2015/16 revealed varying fortunes: gentoo penguin pairs increased by 255%, (3.5% per annum), chinstrap penguins declined by 68% (-3.6% per annum) and Adélie penguins declined by 42% (-1.5% per annum). The chinstrap population has declined steadily over the last four decades. In contrast, Adélie and gentoo penguins have experienced phases of population increase and decline. Annual surveys of selected chinstrap and Adélie colonies produced similar trends from those revealed by island-wide surveys, allowing total island population trends to be inferred relatively well. However, while the annual colony counts of chinstrap and Adélie penguins showed a trend consistent in direction with the results from all-island surveys, the magnitude of estimated population change was markedly different between colony wide and all island counts. Annual population patterns suggest that pair numbers in the study areas partly reflect immigration and emigration of nesting birds between different parts of the island. Breeding success for all three species remained broadly stable over time in the annually monitored colonies. Breeding success rates in gentoo and chinstrap penguins were strongly correlated, despite the differing trends in population size. This study shows the importance of effective, standardised monitoring to accurately determine long-term population trajectories. Our results indicate significant declines in the Adélie and chinstrap penguin populations at Signy Island over the last five decades, and a gradual increase in gentoo breeding pairs.

Population structure and phylogeography of the Gentoo Penguin (Pygoscelis papua) across the Scotia Arc.

Climate change, fisheries' pressure on penguin prey, and direct human disturbance of wildlife have all been implicated in causing large shifts in the abundance and distribution of penguins in the Southern Ocean. Without mark-recapture studies, understanding how colonies form and, by extension, how ranges shift is challenging. Genetic studies, particularly focused on newly established colonies, provide a snapshot of colonization and can reveal the extent to which shifts in abundance and occupancy result from changes in demographic rates (e.g., reproduction and survival) or migration among suitable patches of habitat. Here, we describe the population structure of a colonial seabird breeding across a large latitudinal range in the Southern Ocean. Using multilocus microsatellite genotype data from 510 Gentoo penguin (Pygoscelis papua) individuals from 14 colonies along the Scotia Arc and Antarctic Peninsula, together with mitochondrial DNA data, we find strong genetic differentiation between colonies north and south of the Polar Front, that coincides geographically with the taxonomic boundary separating the subspecies P. p. papua and P. p. ellsworthii. Using a discrete Bayesian phylogeographic approach, we show that southern Gentoos expanded from a possible glacial refuge in the center of their current range, colonizing regions to the north and south through rare, long-distance dispersal. Our findings show that this dispersal is important for new colony foundation and range expansion in a seabird species that ordinarily exhibits high levels of natal philopatry, though persistent oceanographic features serve as barriers to movement.

A clinically based protein discovery strategy to identify potential biomarkers of response to anti-TNF-α treatment of psoriatic arthritis.

PURPOSE: Psoriatic arthritis (PsA) can be treated using biologic therapies targeting biomolecules such as tumor necrosis factor alpha, interleukins (IL)-17 and IL-23. Although 70% PsA patients respond well to therapy, 30% patients show no or limited clinical improvement. Biomarkers that predict response to therapy would help to avoid unnecessary use of expensive biologics in nonresponding patients and enable alternative treatments to be explored. EXPERIMENTAL DESIGN: Patient synovial tissue samples from two clinical studies were analysed using difference in-gel electrophoresis-based proteomics to identify protein expression differences in response to anti-TNF-α treatment. Subsequent multiplexed MRM measurements were used to verify potential biomarkers. RESULTS: A total of 119 proteins were differentially expressed (p<0.05) in response to anti-TNF-α treatment and 25 proteins were differentially expressed (p<0.05) between "good responders" and "poor responders". From these differentially expressed proteins, MRM assays were developed for four proteins to explore their potential as treatment predictive biomarkers. CONCLUSION AND CLINICAL RELEVANCE: Gel-based proteomics strategy has demonstrated differential protein expression in synovial tissue of PsA patients, in response to anti-TNF-α treatment. Development of multiplex MRM assays to these differentially expressed proteins has the potential to predict response to therapy and allow alternative, more effective treatments to be explored sooner.

Co-detection of Target and Total Protein by CyDye Labeling and Fluorescent ECL Plex Immunoblotting in a Standard Proteomics Workflow.

The qualitative and quantitative capabilities of 2-D electrophoresis and its use in widespread proteome analysis have been revolutionized over the past decade with the introduction of differential gel electrophoresis commonly known as DIGE. This highly sensitive CyDye protein labeling technique now attempts to advance conventional western blotting by the combination of DIGE labeling with ECL Plex CyDye conjugated secondary antibodies. The ability of this method to simultaneously visualize the total protein expression profile as well as the specific immunodetection of an individual protein species will significantly aid protein validation following 2-D gel separation by confirming the exact location of proteins of interest. This simple, rapid, and reproducible technique is demonstrated by 1-D and 2-D electrophoresis through the detection of the small 27 kDa heat shock protein (hsp 27), a protein known to be expressed in the human heart, from a complex cardiac protein extract.

INPPO2014, First INPPO World Congress on "Plant Proteomics: Methodology to Biology"-A global platform for involving, gathering and disseminating knowledge.

The International Plant Proteomics Organization (INPPO) is a global platform of the plant proteomics community or, more generally, the scientific community that uses proteomics to address plant biology. Organizing an international conference is one of its initiatives to promote plant proteomics by involving and gathering scientists/researchers/students and by disseminating the acquired knowledge. In this fourth INPPO Highlights, the first INPPO World Congress 2014 (INPPO2014) is described and discussed. The INPPO2014 was held at the University of Hamburg (Germany) with the title "Plant Proteomics: Methodology to Biology" under the leadership of Sabine Lüthje (Germany). Participants (around 150) from 38 nations attended this congress covering all continents. The four-day scientific program comprised 52 lectures and 61 poster presentations in a highly professional and friendly atmosphere on mass spectrometry and gel-based proteomics. Two round-table open discussions deliberated on plant proteomics, its associated international organizations/initiatives and future INPPO perspectives. The Second INPPO World Congress 2016 (INPPO2016) "The Quest for Tolerant Varieties-Phenotyping at Plant and Cellular Level" is planned to be organized in Bratislava (Slovakia) under the leadership of Martin Hajduch (Slovak Republic) and Sébastien Carpentier (Belgium) and cosponsored by the COST action FA1306.

Increasing Accuracy: A New Design and Algorithm for Automatically Measuring Weights, Travel Direction and Radio Frequency Identification (RFID) of Penguins.

A fully automated weighbridge using a new algorithm and mechanics integrated with a Radio Frequency Identification System is described. It is currently in use collecting data on Macaroni penguins (Eudyptes chrysolophus) at Bird Island, South Georgia. The technology allows researchers to collect very large, highly accurate datasets of both penguin weight and direction of their travel into or out of a breeding colony, providing important contributory information to help understand penguin breeding success, reproductive output and availability of prey. Reliable discrimination between single and multiple penguin crossings is demonstrated. Passive radio frequency tags implanted into penguins allow researchers to match weight and trip direction to individual birds. Low unit and operation costs, low maintenance needs, simple operator requirements and accurate time stamping of every record are all important features of this type of weighbridge, as is its proven ability to operate 24 hours a day throughout a breeding season, regardless of temperature or weather conditions. Users are able to define required levels of accuracy by adjusting filters and raw data are automatically recorded and stored allowing for a range of processing options. This paper presents the underlying principles, design specification and system description, provides evidence of the weighbridge's accurate performance and demonstrates how its design is a significant improvement on existing systems.

The persisting effects of electroconvulsive stimulation on the hippocampal proteome.

Electroconvulsive therapy (ECT) is the most acutely effective treatment available for severe depression. However, its mechanism of action is not fully understood. Elucidating the protein changes induced in the brain by ECT will enhance our understanding of this antidepressant therapy. Electroconvulsive stimulation (ECS), the animal analogue of ECT, was administered to rats to determine the proteomic changes induced in the hippocampus, a region of the brain implicated in the biology of depression and its treatment. Two-dimensional difference in gel electrophoresis (2D-DiGE) and liquid chromatography tandem mass spectrometry (LC-MS/MS) methods were applied to identify differentially expressed proteins following acute (×1 treatment), chronic (×10 treatments) or chronic(+4 weeks) (×10 treatments plus 4 weeks later) ECS. Administration of acute, chronic and chronic(+4 weeks) ECS induced significant changes in multiple DiGE gel protein spots. Interestingly, the largest number of differentially expressed protein spots was identified following chronic(+4 weeks) ECS. Following protein identification by LC-MS/MS, gene ontology analysis primarily implicated proteins with cytoskeletal and metabolism-related roles in the action of ECS. Immunoblotting confirmed the changes in abundance of the cytoskeletal protein actin following chronic(+4 weeks) ECS. Overall, chronic(+4 weeks) ECS was particularly effective at inducing longer-lasting changes in the abundance of hippocampal proteins with cytoskeletal and metabolism roles. These results suggest a role for persisting cytoskeletal-related neuroplastic changes in the action of ECS and may be informative as to the antidepressant mechanisms of ECT in patients with depression.

Acute phase plasma proteins are altered by electroconvulsive stimulation.

Electroconvulsive therapy (ECT) is an effective antidepressant treatment, but its molecular mechanisms of action remain to be fully elucidated. To better understand the effects of ECT, we conducted a proteomic study to characterize global changes in plasma protein abundance induced by electroconvulsive stimulation (ECS) in the animal model equivalent of ECT. Male Sprague-Dawley rats were administered a single or repeat (10 sessions) course of ECS, and compared with sham-ECS administered animals. Quantitative differential protein expression analysis was performed, using 2-dimensional difference in gel electrophoresis (2D DiGE), on immunodepleted plasma. Proteins were selected for identification by liquid chromatography tandem mass spectrometry (LC-MS/MS): 150 protein spots were significantly altered following a single ECS and 178, following repeated ECS. In total, 18 proteins were identified by LC-MS/MS. Many of these were acute-phase response proteins, previously reported to be increased in depressed patients. Changes in the abundance of two proteins of interest were confirmed by other measures. Repeat ECS was found to significantly reduce plasma levels of haptoglobin and apolipoprotein A-IV, although these changes were no longer evident 4 weeks after the repeated ECS. Our results implicate the immune system-induced acute phase protein response in ECS action while identifying potential plasma biomarkers for ECS.

Proteomic investigation of the hippocampus in prenatally stressed mice implicates changes in membrane trafficking, cytoskeletal, and metabolic function.

Prenatal stress influences the development of the fetal brain and so contributes to the risk of the development of psychiatric disorders in later life. The hippocampus is particularly sensitive to prenatal stress, and robust abnormalities have been described in the hippocampus in schizophrenia and depression. The aim of this study was to determine whether prenatal stress is associated with distinct patterns of differential protein expression in the hippocampus using a validated mouse model. We therefore performed a comparative proteomic study assessing female hippocampal samples from 8 prenatally stressed mice and 8 control mice. Differential protein expression was assessed using 2-dimensional difference in gel electrophoresis and subsequent mass spectrometry. The observed changes in a selected group of differentially expressed proteins were confirmed by Western blotting. In comparison to controls, 47 protein spots (38 individual proteins) were found to be differentially expressed in the hippocampus of prenatally stressed mice. Functional grouping of these proteins revealed that prenatal stress influenced the expression of proteins involved in brain development, cytoskeletal composition, stress response, and energy metabolism. Western blotting was utilized to validate the changes in calretinin, hippocalcin, profilin-1 and the signal-transducing adaptor molecule STAM1. Septin-5 could not be validated via Western blotting due to methodological issues. Closer investigation of the validated proteins also pointed to an interesting role for membrane trafficking deficits mediated by prenatal stress. Our findings demonstrate that prenatal stress leads to altered hippocampal protein expression, implicating numerous molecular pathways that may provide new targets for psychotropic drug development.