Drought recorded by Ba/Ca in coastal benthic foraminifera

Increasing occurrences of extreme weather events, such as the 2018 drought over northern Europe, are a concerning issue under global climate change. High-resolution archives of natural hydroclimate proxies, such as rapidly accumulating sediments containing biogenic carbonates, offer the potential to investigate the frequency and mechanisms of such events in the past. Droughts alter the barium (Ba) concentration of near-continent seawater through the reduction in Ba input from terrestrial runoff, which in turn may be recorded as changes in the chemical composition (Ba/Ca) of foraminiferal calcium carbonates accumulating in sediments. However, so far the use of Ba/Ca as a discharge indicator has been restricted to planktonic foraminifera, despite the high relative abundance of benthic species in coastal, shallow-water sites. Moreover, benthic foraminiferal Ba/Ca has mainly been used in openocean records as a proxy for paleo-productivity. Here we report on a new geochemical data set measured from living (CTG-labeled) benthic foraminiferal species to investigate the capability of benthic Ba/Ca to record changes in river runoff over a gradient of contrasting hydroclimatic conditions. Individual foraminifera (Bulimina marginata, Non-ionellina labradorica) were analyzed by laser-ablation ICP-MS over a seasonal and spatial gradient within Gullmar Fjord, Swedish west coast, during 2018-2019. The results are compared to an extensive meteorological and hydrological data set, as well as sediment and pore-water geochemistry. Benthic foraminiferal Ba/Ca correlates significantly to riverine runoff; however, the signals contain both spatial trends with distance to Ba source and species-specific influences such as micro-habitat preferences. We deduce that shallow-infaunal foraminifera are especially suitable as proxy for terrestrial Ba input and discuss the potential influence of water-column and pore-water Ba cycling. While distance to Ba source, water depth, pore-water geochemistry, and species-specific effects need to be considered in interpreting the data, our results demonstrate confidence in the use of Ba/Ca of benthic foraminifera from near-continent records as a proxy for past riverine discharge and to identify periods of drought.Peer reviewe

Temperature calibration of Mg/Ca ratios in the intermediate water benthic foraminifer Hyalinea balthica

Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 12 (2011): Q04003, doi:10.1029/2010GC003333.Core top samples from Indonesian and northeast Atlantic depth transects were used to calibrate Mg/Ca and δ18O in tests of the calcitic benthic foraminifer Hyalinea balthica to bottom water temperature between 4°C and 13°C. This shallow infaunal species is primarily abundant in neritic to upper bathyal sediments (<600 m). Both linear and exponential calibrations suggest a temperature sensitivity of ~12% per °C that is ~4 times higher than observed in other species of deep-sea benthic foraminifera. Culture experiments support the core top calibration. We find no discernible effect of salinity and saturation on Mg/Ca. Comparison between the measured benthic foraminiferal δ18O and predicted equilibrium values suggests that on average H. balthica δ18O is 0.64‰ ± 0.13‰ lower than predicted from the equilibrium composition. To test the reliability of using paired H. balthica Mg/Ca and δ18O measurements for reconstructing seawater δ18Osw and salinity, we apply this calibration to another depth transect from Cape Ghir off NW Africa, which was not included in the calibration. Based on error analysis of the calibration data and this validation test, we show that the uncertainty of reconstructing bottom water temperature and salinity from paired Mg/Ca and δ18O measurements of H. balthica is better than ±0.7°C and ±0.69 practical salinity scale, respectively. The small uncertainties allow for the reconstruction of seawater density to better than 0.3σθ units, which is precise enough for the identification of specific water masses and reconstruction of changes in their properties. We propose that the relatively high Mg content and temperature sensitivity of H. balthica might be due to minor, biologically mediated contribution of high-Mg calcite to the primarily low Mg calcite test, which is influenced by the ambient temperature. This hypothesis, if correct, suggests that benthic species with relatively high Mg/Ca may be better suited for deepwater temperature reconstructions than species that have thus far been more commonly used.This project was funded by NSF Awards OCE 02‐20922 and 09‐02977 to YR, OCE 09‐28607 to MK, OCE02‐20776 to DWO, and DFG priority program INTERDYNAMIK to AM

Feasibility and results of a randomised pilot-study of pre-discharge occupational therapy home visits

BACKGROUND: Pre-discharge home visits aim to maximise independence in the community. These visits involve assessment of a person in their own home prior to discharge from hospital, typically by an occupational therapist. The therapist may provide equipment, adapt the home environment and/or provide education. The aims of this study were to investigate the feasibility of a randomised controlled trial in a clinical setting and the effect of pre-discharge home visits on functional performance in older people undergoing rehabilitation. METHODS: Ten patients participating in an inpatient rehabilitation program were randomly assigned to receive either a pre-discharge home visit (intervention), or standard practice in-hospital assessment and education (control), both conducted by an occupational therapist. The pre-discharge home visit involved assessment of the older person's function and environment, and education, and took an average of 1.5 hours. The hospital-based interview took an average of 40 minutes. Outcome data were collected by a blinded assessor at 0, 2, 4, 8 and 12 weeks. Outcomes included performance of activities of daily living, reintegration to community living, quality of life, readmission and fall rates. RESULTS: Recruitment of 10 participants was slow and took three months. Observed performance of functional abilities did not differ between groups due to the small sample size. Difference in activities of daily living participation, as recorded by the Nottingham Extended Activities of Daily Living scale, was statistically significant but wide confidence intervals and low statistical power limit interpretation of results. CONCLUSION: Evaluation of pre-discharge home visits by occupational therapists in a rehabilitation setting is feasible, but a more effective recruitment strategy for a main study is favored by application of a multi-centre setting

The Coq Proof Assistant Reference Manual : Version 6.1

Projet COQCoq is a proof assistant based on a higher-order logic allowing powerful definitions of functions. Coq V6.1 is available by anonymous ftp at ftp.inria.fr:/INRIA/Projects/coq/V6.1 and ftp.ens-lyon.fr:/pub/LIP/COQ/V6.

N-Acyl Homoserine Lactones in Diverse Pectobacterium and Dickeya Plant Pathogens: Diversity, Abundance, and Involvement in Virulence

Soft-rot bacteria Pectobacterium and Dickeya use N-acyl homoserine lactones (NAHSLs) as diffusible signals for coordinating quorum sensing communication. The production of NAHSLs was investigated in a set of reference strains and recently-collected isolates, which belong to six species and share the ability to infect the potato host plant. All the pathogens produced different NAHSLs, among which the 3-oxo-hexanoyl- and the 3-oxo-octanoyl-l-homoserine lactones represent at least 90% of total produced NAHSL-amounts. The level of NAHSLs varied from 0.6 to 2 pg/cfu. The involvement of NAHSLs in tuber maceration was investigated by electroporating a quorum quenching vector in each of the bacterial pathogen strains. All the NAHSL-lactonase expressing strains produced a lower amount of NAHSLs as compared to those harboring the empty vector. Moreover, all except Dickeya dadantii 3937 induced a lower level of symptoms in potato tuber assay. Noticeably, aggressiveness appeared to be independent of both nature and amount of produced signals. This work highlights that quorum sensing similarly contributed to virulence in most of the tested Pectobacterium and Dickeya, even the strains had been isolated recently or during the past decades. Thus, these key regulatory-molecules appear as credible targets for developing anti-virulence strategies against these plant pathogens

Type I interferon/IRF7 axis instigates chemotherapy-induced immunological dormancy in breast cancer

Neoadjuvant and adjuvant chemotherapies provide survival benefits to breast cancer patients, in particular in estrogen receptor negative (ER-) cancers, by reducing rates of recurrences. It is assumed that the benefits of (neo)adjuvant chemotherapy are due to the killing of disseminated, residual cancer cells, however, there is no formal evidence for it. Here, we provide experimental evidence that ER- breast cancer cells that survived high-dose Doxorubicin and Methotrexate based chemotherapies elicit a state of immunological dormancy. Hallmark of this dormant phenotype is the sustained activation of the IRF7/IFN-beta/IFNAR axis subsisting beyond chemotherapy treatment. Upregulation of IRF7 in treated cancer cells promoted resistance to chemotherapy, reduced cell growth and induced switching of the response from a myeloid derived suppressor cell-dominated immune response to a CD4(+)/CD8(+) T cell-dependent anti-tumor response. IRF7 silencing in tumor cells or systemic blocking of IFNAR reversed the state of dormancy, while spontaneous escape from dormancy was associated with loss of IFN-beta production. Presence of IFN-beta in the circulation of ER- breast cancer patients treated with neoadjuvant Epirubicin chemotherapy correlated with a significantly longer distant metastasis-free survival. These findings establish chemotherapy-induced immunological dormancy in ER- breast cancer as a novel concept for (neo)adjuvant chemotherapy activity, and implicate sustained activation of the IRF7/IFN-beta/IFNAR pathway in this effect. Further, IFN-beta emerges as a potential predictive biomarker and therapeutic molecule to improve outcome of ER- breast cancer patients treated with (neo)adjuvant chemotherapy.Peer reviewe

Whole Genome Sequencing and Complete Genetic Analysis Reveals Novel Pathways to Glycopeptide Resistance in Staphylococcus aureus

The precise mechanisms leading to the emergence of low-level glycopeptide resistance in Staphylococcus aureus are poorly understood. In this study, we used whole genome deep sequencing to detect differences between two isogenic strains: a parental strain and a stable derivative selected stepwise for survival on 4 µg/ml teicoplanin, but which grows at higher drug concentrations (MIC 8 µg/ml). We uncovered only three single nucleotide changes in the selected strain. Nonsense mutations occurred in stp1, encoding a serine/threonine phosphatase, and in yjbH, encoding a post-transcriptional negative regulator of the redox/thiol stress sensor and global transcriptional regulator, Spx. A missense mutation (G45R) occurred in the histidine kinase sensor of cell wall stress, VraS. Using genetic methods, all single, pairwise combinations, and a fully reconstructed triple mutant were evaluated for their contribution to low-level glycopeptide resistance. We found a synergistic cooperation between dual phospho-signalling systems and a subtle contribution from YjbH, suggesting the activation of oxidative stress defences via Spx. To our knowledge, this is the first genetic demonstration of multiple sensor and stress pathways contributing simultaneously to glycopeptide resistance development. The multifactorial nature of glycopeptide resistance in this strain suggests a complex reprogramming of cell physiology to survive in the face of drug challenge

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival