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Immunological memory is critical for immune protection, particularly at epithelial sites, which are under constant risk of pathogen invasions. To counter invading pathogens, CD8+ memory T cells develop at the location of infection: tissue-resident memory T cells (TRM). CD8+ T-cell responses are associated with type-1 infections and type-1 regulatory T cells (TREG) are important for CD8+ T-cell development, however, if CD8+ TRM cells develop under other infection types and require immune type-specific TREG cells is unknown. We used three distinct lung infection models, to show that type-2 helminth infection does not establish CD8+ TRM cells. Intracellular (type-1) and extracellular (type-3) infections do and rely on the recruitment of response type-matching TREG population contributing transforming growth factor-β. Nevertheless, type-1 TREG cells remain the most important population for TRM cell development. Once established, TRM cells maintain their immune type profile. These results may have implications in the development of vaccines inducing CD8+ TRM cells. Type-1 regulatory T cells promoted the generation of CD8+ tissue-resident memory T (TRM) cells during intracellular infections in the gut. Here, the authors show that the establishment TRM cells more broadly depends on the presence of regulatory T cells matching the type of infection. [ABSTRACT FROM AUTHOR]

Background: The past years have witnessed dramatic changes in the population admitted to the intensive care unit (ICU). Older and sicker patients are now commonly treated in this setting due to the newly available sophisticated life support. However, the short- and long-term benefit of this strategy is scarcely studied. Methods: The Critically Ill patients' mortality by age: Long-Term follow-up (CIMbA-LT) was a multicentric, nationwide, retrospective, observational study addressing short- and long-term prognosis of patients admitted to Portuguese multipurpose ICUs, during 4 years, according to their age and disease severity. Patients were followed for two years after ICU admission. The standardized hospital mortality ratio (SMR) was calculated according to the Simplified Acute Physiology Score (SAPS) II and the follow-up risk, for patients discharged alive from the hospital, according to official demographic national data for age and gender. Survival curves were plotted according to age group. Results: We included 37.118 patients, including 15.8% over 80 years old. The mean SAPS II score was 42.8 ± 19.4. The ICU all-cause mortality was 16.1% and 76% of all patients survive until hospital discharge. The SAPS II score overestimated hospital mortality [SMR at hospital discharge 0.7; 95% confidence interval (CI) 0.63–0.76] but accurately predicted one-year all-cause mortality [1-year SMR 1.01; (95% CI 0.98–1.08)]. Survival curves showed a peak in mortality, during the first 30 days, followed by a much slower survival decline thereafter. Older patients had higher short- and long-term mortality and their hospital SMR was also slightly higher (0.76 vs. 0.69). Patients discharged alive from the hospital had a 1-year relative mortality risk of 6.3; [95% CI 5.8–6.7]. This increased risk was higher for younger patients [21.1; (95% CI 15.1–39.6) vs. 2.4; (95% CI 2.2–2.7) for older patients]. Conclusions: Critically ill patients' mortality peaked in the first 30 days after ICU admission. Older critically ill patients had higher all-cause mortality, including a higher hospital SMR. A long-term increased relative mortality risk was noted in patients discharged alive from the hospital, but this was more noticeable in younger patients. [ABSTRACT FROM AUTHOR]

High Arctic ecosystems and Indigenous livelihoods are tightly linked and exposed to climate change, yet assessing their sensitivity requires a long-term perspective. Here, we assess the vulnerability of the North Water polynya, a unique seaice ecosystem that sustains the world's northernmost Inuit communities and several keystone Arctic species. We reconstruct mid-to-late Holocene changes in sea ice, marine primary production, and little auk colony dynamics through multi-proxy analysis of marine and lake sediment cores. Our results suggest a productive ecosystem by 4400–4200 cal yrs b2k coincident with the arrival of the first humans in Greenland. Climate forcing during the late Holocene, leading to periods of polynya instability and marine productivity decline, is strikingly coeval with the human abandonment of Greenland from c. 2200–1200 cal yrs b2k. Our long-term perspective highlights the future decline of the North Water ecosystem, due to climate warming and changing sea-ice conditions, as an important climate change risk. The North Water polynya is a unique but vulnerable ecosystem, home to Indigenous people and Arctic keystone species. New palaeoecological records from Greenland suggest human abandonment c. 2200–1200 cal yrs BP occurred during climate-forced polynya instability, foreshadowing future ecosystem declines. [ABSTRACT FROM AUTHOR]

Baffin Bay hosts the largest and most productive of the Arctic polynyas: the North Water (NOW). Despite its significance and active role in water mass formation, the history of the NOW beyond the observational era remains poorly known. We reconcile the previously unassessed relationship between long-term NOW dynamics and ocean conditions by applying a multiproxy approach to two marine sediment cores from the region that, together, span the Holocene. Declining influence of Atlantic Water in the NOW is coeval with regional records that indicate the inception of a strong and recurrent polynya from ~ 4400 yrs BP, in line with Neoglacial cooling. During warmer Holocene intervals such as the Roman Warm Period, a weaker NOW is evident, and its reduced capacity to influence bottom ocean conditions facilitated northward penetration of Atlantic Water. Future warming in the Arctic may have negative consequences for this vital biological oasis, with the potential knock-on effect of warm water penetration further north and intensified melt of the marine-terminating glaciers that flank the coast of northwest Greenland. [ABSTRACT FROM AUTHOR]

DNA can be preserved in marine and freshwater sediments both in bulk sediment and in intact, viable resting stages. Here, we assess the potential for combined use of ancient, environmental, DNA and timeseries of resurrected long-term dormant organisms, to reconstruct trophic interactions and evolutionary adaptation to changing environments. These new methods, coupled with independent evidence of biotic and abiotic forcing factors, can provide a holistic view of past ecosystems beyond that offered by standard palaeoecology, help us assess implications of ecological and molecular change for contemporary ecosystem functioning and services, and improve our ability to predict adaptation to environmental stress. Ellegaard et al. discuss the potential for using ancient environmental DNA (eDNA), combined with resurrection ecology, to analyse trophic interactions and evolutionary adaptation to changing environments. Their Review suggests that these techniques will improve our ability to predict genetic and phenotypic adaptation to environmental stress. [ABSTRACT FROM AUTHOR]

Holistic processing, a hallmark of expert processing, has been shown for written words, signaled by the word composite effect, similar to the face composite effect: fluent readers find it difficult to focus on just one half of a written word while ignoring the other half, especially when the two word halves are aligned rather than misaligned. This effect is signaled by a significant interaction between alignment and congruency of the two word parts. Face and visual word recognition, however, involve different neural mechanisms with an opposite hemispheric lateralization. It is then possible that faces and words can both involve holistic processing in their own separate face and word processing systems, but by using different mechanisms. In the present study, we replicated with words a previous study done with faces (Richler, Bukach, & Gauthier, 2009, Experiment 3). In a first experiment we showed that in a composite task with aligned artificial objects, no congruency effects are found. In a second experiment, using an interleaved task, a congruency effect for Ziggerins was induced in trials in which a word was first encoded, but more strongly when it was aligned. However, in a stricter test, we found no differences between the congruency effect for Ziggerins induced by aligned words versus pseudowords. Our results demonstrate that different mechanisms can underlie holistic processing in different expertise domains. [ABSTRACT FROM AUTHOR]

The integration and evolution of implantable medical devices made of bioresorbable polymers and used for temporary biomedical applications are crucial criteria in the success of a therapy and means of follow-up after implantation are needed. The objective of this work is to develop and evaluate a method based on microscopic Fourier Transform InfraRed spectroscopy (FTIR) mappings to monitor the degradation of such polymers on tissue explant sections, after implantation. This technique provided information on their location and on both their composition and crystallinity, which is directly linked to their state of degradation induced predominantly by chain scissions. An in vitro study was first performed on poly(L-lactic acid) (PLLA) meshes to validate the procedure and the assumption that changes observed on FTIR spectra are indeed a consequence of degradation. Then, mappings of in vivo degraded PLLA meshes were realized to follow up their degradation and to better visualize their degradation mechanisms. This work further warrants its translation to medical implants made of copolymers of lactic acid and to other polyesters. Graphical Abstract: [ABSTRACT FROM AUTHOR]

In order to establish a baseline for proxy-based reconstructions for the Young Sound-Tyrolerfjord system (Northeast Greenland), we analysed the spatial distribution of primary production and sea ice proxies in surface sediments from the fjord, against monitoring data from the Greenland Ecosystem Monitoring Programme. Clear spatial gradients in organic carbon and biogenic silica contents reflected marine influence, nutrient availability and river-induced turbidity, in good agreement with in situ measurements. The sea ice proxy IP was detected at all sites but at low concentrations, indicating that IP records from fjords need to be carefully considered and not directly compared to marine settings. The sea ice-associated biomarker HBI III revealed an open-water signature, with highest concentrations near the mid-July ice edge. This proxy evaluation is an important step towards reliable palaeoenvironmental reconstructions that will, ultimately, contribute to better predictions for this High Arctic ecosystem in a warming climate. [ABSTRACT FROM AUTHOR]

We report an atypical case of Rhodotorula mucilaginosa fungemia coexisting with pleural tuberculosis, in an immunocompetent host. The patient was an inhaled drug abuser and worked in a fruit market. The diagnosis of Rhodotorula mucilaginosa infection was established by the isolation of the yeast in two blood cultures followed by a good response to amphotericin B treatment. Persistent evening fever and pleural effusion led to the second diagnosis-pleural tuberculosis. In the last 5 years, this was the only case of Rhodotorula mucilaginosa fungemia in our hospital and the first case in the literature that documents Rhodotorula mucilaginosa fungemia associated with pleural tuberculosis. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the effect of oral zinc supplementation on antioxidant defenses and oxidative stress markers during chemotherapy for colorectal cancer. Twenty-four patients who had undergone surgical resection of colorectal cancer participated in this placebo-controlled, prospective randomized study. The supplementation was started in the perioperative period, in which 10 patients received 70 mg of zinc (zinc group, n = 10) and 14 patients received placebo (placebo group, n = 14) for 16 weeks. Approximately 45 days after surgical resection of tumor, all patients received a chemotherapeutic regimen (capecitabine, capecitabine combined with oxaliplatin or 5-fluorouracil). Vitamin C, vitamin E, antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), and lipid peroxidation markers malondialdehyde (MDA) and 8-isoprostane were determined before the first, second, third, and fourth chemotherapy cycles. Compared with the placebo group, the zinc group presented higher SOD values before the first, second, and fourth chemotherapy cycles and lower GPx values before the third cycle. There were no statistical differences between the study groups in vitamin C, vitamin E, MDA, or 8-isoprostane plasma values. Longitudinal analysis revealed decreased vitamin E concentration in the placebo group before the second and fourth cycles as compared with the initial values. Zinc supplementation during chemotherapy cycles increased SOD activity and maintained vitamin E concentrations. Although no effect of zinc supplementation on oxidative stress markers was observed, the increase in SOD activity indicates a production of stable free radicals, which may have a positive effect in cancer treatment. [ABSTRACT FROM AUTHOR]

Integrated sediment multiproxy studies and modeling were used to reconstruct past changes in the Baltic Sea ecosystem. Results of natural changes over the past 6000 years in the Baltic Sea ecosystem suggest that forecasted climate warming might enhance environmental problems of the Baltic Sea. Integrated modeling and sediment proxy studies reveal increased sea surface temperatures and expanded seafloor anoxia (in deep basins) during earlier natural warm climate phases, such as the Medieval Climate Anomaly. Under future IPCC scenarios of global warming, there is likely no improvement of bottom water conditions in the Baltic Sea. Thus, the measures already designed to produce a healthier Baltic Sea are insufficient in the long term. The interactions between climate change and anthropogenic impacts on the Baltic Sea should be considered in management, implementation of policy strategies in the Baltic Sea environmental issues, and adaptation to future climate change. [ABSTRACT FROM AUTHOR]

Pentapharsodinium dalei is a widely distributed cold-water dinoflagellate, which is used in palaeoecology as an indicator of relatively warmer conditions in polar and sub-polar regions. This species has been proposed to be one of the first indicators of global warming at high latitudes. We developed the first microsatellite markers for P. dalei to facilitate the study of spatial and temporal population genetic changes. Single cysts were isolated from surface sediments in Koljö Fjord, Sweden. After cyst germination, single vegetative cells were isolated for establishing monoclonal cultures. Six dinucleotide polymorphic microsatellite markers were developed as multiplex polymerase chain reactions and were genotyped in 32 strains. The number of alleles per locus varied between 4 and 12, and the estimated gene diversity varied from 0.588 to 0.891. The haploid state of the vegetative cells was confirmed. The six selected microsatellites will be useful to explore population dynamics in P. dalei from contemporary planktonic and revived benthic samples to enable, for example, detailed studies into the evolutionary consequences of anthropogenic and climate-driven habitat changes. [ABSTRACT FROM AUTHOR]

The phytoplankton species Gymnodinium catenatum is responsible for major worldwide losses in aquaculture due to shellfish toxicity. On the West coast of the Iberian Peninsula, toxic blooms have been reported since the mid-1970s. While the recent geographical spread of this species into Australasia has been attributed to human-mediated introduction, its origin in the Northeast Atlantic is still under debate. Gymnodinium catenatum forms a highly resistant resting stage (cyst) that can be preserved in coastal sediments, building-up an historical record of the species. Similar cyst types (termed microreticulate) are produced by other non-toxic Gymnodinium species that often co-occur with G. catenatum. We analysed the cyst record of microreticulate species in dated sediment cores from the West Iberian shelf covering the past ca. 150 years. Three distinct morphotypes were identified on the basis of cyst diameter and paracingulum reticulation. These were attributed to G. catenatum (35.6-53.3 μm), G. nolleri (23.1-36.4 μm), and G. microreticulatum (20.5-34.3 μm). Our results indicate that G. catenatum is new to the NE Atlantic, where it appeared by 1,889 ± 10, expanding northwards along the West Iberian coast. The earliest record is from the southernmost sample, while in the central Portuguese shelf the species appears in sediments dated to 1,933 ± 3, and in the North, off Oporto, in 1,951 ± 4. On the basis of the cyst record and toxic bloom reports, we reconstruct the invasive pathway of G. catenatum in the NE Atlantic. Although human-mediated introduction cannot be discarded, the available evidence points towards natural range expansion, possibly from NW Africa. [ABSTRACT FROM AUTHOR]

ColE1-like plasmids are widely used as expression vectors and as gene delivery vehicles. We have recently described a naturally occurring plasmid deletion phenomenon in the ColE1-type plasmid, pCI-neo, which leads to the detectable expression of an apparently promotorless kanamycin resistance gene. In the current work, we found that the expression of that aminoglycoside phosphotransferase ( aph) gene is regulated by an RNAII preprimer promoter located within the plasmid ColE1 replication origin, as a consequence of the extension of the RNA II species for at least 1.5 kb, up to the aph gene. This mechanism is dependent on the nonformation and/or dissociation of the hybrid between plasmid DNA and RNA II preprimer transcript. This is the first in vivo description of RNA II transcription beyond ori in wild-type Escherichia coli strains and nonmutated RNAII plasmid sequences resulting in productive transcription of distant downstream genes. Our results raise questions about unwanted expression of genes from expression or cloning vectors of ColE1 type and highlight the importance of a more careful design of ColE1-derived plasmid vectors. [ABSTRACT FROM AUTHOR]

The stability in Escherichia coli of a mammalian expression vector (pCIneo) and its derivative candidate DNA vaccine (pGPV-PV) is described. These multicopy pMB1-type plasmids were found to recombine in several recA E. coli strains due to the presence of two 28 bp direct repeats flanking intervening sequences of 1.6 kb (pCIneo) and 3.2 kb (pGPV-PV). In this recombination event, one of the direct repeats and the intervening sequence were deleted or duplicated, originating monomeric or/and hetero-dimeric plasmid forms, respectively. Additionally, the plasmid rearrangement led to the acquisition of a kanamycin resistance phenotype. Recombination frequencies between 7.8 × 10−7 and 3.1 × 10−5 were determined for DH5α and JM109(DE3) strains, respectively. Higher recombination frequencies were found in cells previously grown up to stationary growth phase being the monomeric plasmid form the prevalent one. Real-time PCR quantification revealed the presence of approximately 1.5 × 104 recombined molecules per 2 × 105 cells pre-kanamycin exposure. Under selective pressure of this antibiotic, the number of recombined molecules increased approximately 2,000-fold in a 48-h period replacing the original plasmid form. The high frequency, at which deletion-duplication occurred in the absence of kanamycin selective pressure, should be regarded as a safety concern. This work highlights the impact of mutational hot spots on expression and cloning plasmid vectors and the need to carefully design plasmid vectors. [ABSTRACT FROM AUTHOR]

The development of aqueous two-phase systems for plasmid purification from Escherichia coli cell lysates requires a reliable DNA quantitation method. Plasmid DNA was quantified by fluorescence using PicoGreen nucleic acid stain. Linearity was obtained up to 40 ng plasmid ml-1. Two polyethyleneglycol (PEG)/salt systems were studied, PEG 600/K2HPO4 and PEG 300/K2HPO4. The average plasmid recovery was 41% in the bottom phase of the first system and 35% in the top phase of the second system. This method has proved to be simple and reproducible. [ABSTRACT FROM AUTHOR]

The 4th Translational Research Symposium (TRS) was organised at the annual meeting of the European Society for Biomaterials (ESB) 2017, Athens, Greece, with a focus on ‘Academia—Industry Clusters of Research for Innovation Catalysis’. Collaborations between research institutes and industry can be sustained in several ways such as: European Union (EU) funded consortiums; syndicates of academic institutes, clinicians and industries; funding from national governments; and private collaborations between universities and companies. Invited speakers from industry and research institutions presented examples of these collaborations in the translation of research ideas or concepts into marketable products. The aim of the present article is to summarize the key messages conveyed during these lectures. In particular, emphasis is put on the challenges to appropriately identify and select unmet clinical needs and their translation by ultimately implementing innovative and efficient solutions achieved through joint academic and industrial efforts. [ABSTRACT FROM AUTHOR]