The Role of Microbial Exopolymers in Determining the Fate of Oil and Chemical Dispersants in the Ocean

The production of extracellular polymeric substances (EPS) by planktonic microbes can influence the fate of oil and chemical dispersants in the ocean through emulsification, degradation, dispersion, aggregation, and/or sedimentation. In turn, microbial community structure and function, including the production and character of EPS, is influenced by the concentration and chemical composition of oil and chemical dispersants. For example, the production of marine oil snow and its sedimentation and flocculent accumulation to the seafloor were observed on an expansive scale after the Deepwater Horizon oil spill in the Northern Gulf of Mexico in 2010, but little is known about the underlying control of these processes. Here, we review what we do know about microbially produced EPS, how oil and chemical dispersant can influence the production rate and chemical and physical properties of EPS, and ultimately the fate of oil in the water column. To improve our response to future oil spills, we need a better understanding of the biological and physiochemical controls of EPS production by microbes under a range of environmental conditions, and in this paper, we provide the key knowledge gaps that need to be filled to do so

Investigation of the presence of an aliphatic biopolymer in cyanobacteria: Implications for kerogen formation

Algaenan has been suggested to be one of the main precursors of certain kerogens. It is a non-hydrolysable and insoluble biomolecule of high molecular weight. It has been found in a limited number of microalgae species. There is considerable uncertainty about its formation and preservation, as well as its role in kerogen formation and the implications for the global C cycle. We tested whether the cyanobacterium Chlorogloeopsis fritschii can synthesise a biomacromolecule similar to algaenan with potential to contribute to kerogen via selective preservation. Two freshwater green microalgae, Pseudochoricystis ellipsoidea and Scenedesmus obliquus, as well as C. fritschii, were subjected to harsh solvent extraction and hydrolysis steps to obtain an insoluble and non-hydrolysable macromolecule. The residues from all three species were analysed using pyrolysis–gas chromatography–mass spectrometry and solid-state nuclear magnetic resonance spectroscopy. The analysis revealed that C. fritschii indeed contains a resistant biomacromolecule exhibiting the characteristic aliphatic structure of algaenan, similar to the algaenan residues from the two microalgae. Due to the robust nature of Chlorogloeopsis compared with eukaryotes, it can prevail in extreme environmental conditions such as freezing, thawing, desiccation and overheating – conditions prevalent on the primeval earth. The presence of a resistant aliphatic biopolymer in Chlorogloeopsis suggests that cyanobacteria could have contributed to kerogen via selective preservation

Lampe1: An ENU-Germline Mutation Causing Spontaneous Hepatosteatosis Identified through Targeted Exon-Enrichment and Next-Generation Sequencing

Using a small scale ENU mutagenesis approach we identified a recessive germline mutant, designated Lampe1 that exhibited growth retardation and spontaneous hepatosteatosis. Low resolution mapping based on 20 intercrossed Lampe1 mice revealed linkage to a ∼14 Mb interval on the distal site of chromosome 11 containing a total of 285 genes. Exons and 50 bp flanking sequences within the critical region were enriched with sequence capture microarrays and subsequently analyzed by next-generation sequencing. Using this approach 98.1 percent of the targeted DNA was covered with a depth of 10 or more reads per nucleotide and 3 homozygote mutations were identified. Two mutations represented intronic nucleotide changes whereas one mutation affected a splice donor site in intron 11–12 of Palmitoyl Acetyl-coenzyme A oxygenase-1 (Acox1), causing skipping of exon 12. Phenotyping of Acox1Lampe1 mutants revealed a progression from hepatosteatosis to steatohepatitis, and ultimately hepatocellular carcinoma. The current approach provides a highly efficient and affordable method to identify causative mutations induced by ENU mutagenesis and animal models relevant to human pathology

Role of genetic testing for inherited prostate cancer risk: Philadelphia prostate cancer consensus conference 2017

Purpose: Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-dri

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

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

Nonsurgical therapy of periodontitis: comparison methods

In our experimental conditions, comparative clinical trials did not demonstrate any differences between forms of treatment. The differences that were found were relatively minor and had no statistical basis, irrespective of the endpoints studied (reduction in number of deep or medium-sized pockets, improvement or stability of attachment, or reduction in mean probing depth). So its reasonable to assume that any increase in sample size would at most bring out differences which might be statistically significant, but which would have little significant clinical impact. It is interesting to note that the level of plaque control achieved by patients was very satisfactory in all the trials, as was the reduction in signs of inflammation. At this stage, the various forms of treatment available may then be used to obtain a marked improvement in the pathological situation and to try to stabilise bone loss, with the help of supportive periodontal therapy. The objective of nonsurgical treatment was therefore achieved, and the requirement for periodontal surgery was reduced to a few zones; the public health implications of this achievement are far from negligible. Our trials confirmed that the manual and power-driven forms of treatment described by other authors are virtually equivalent to each other. The introduction of the Periopolisher® system into the range of treatments available is valuable in terms of ergonomics, but it is still equivalent to these existing forms to treatment. Trying to decide whether any individual method is better than any other would appear to be a relatively sterile exercise. The second aim of our trial was to evaluate the condition of the surface, i.e. how clean and how regular it is, from clinical observation after treatment with carious instruments. No significant differences were found in the number of samples observed, and under our experimental conditions, although some techniques (ultrasonics, and ultrasonics followed by Periopolisher®) seemed to produce fewer surface irregularities. With regard to surface, the various instruments used were a long way from being able to remove all the calcified debris from the surface; a clean surface was obtained in very few cases. The ideal of root planning – to obtain a smooth and clean surface – was therefore nowhere near being achieved. The most important objective is therefore to achieve an improvement in clinical signs, whether or not a perfectly smooth surface condition was obtained. It should be noted that in relation to implants, the fact that the implant surface is perfectly polished does not prevent the onset of peri-implantitis. If good plaque control is not achieved, colonisation of the subgingival space occurs event though the state of the surface (here, the surface of the implant) is the ideal surface we want to produce in the root surfaces. The last aim of our study was to assess how aggressive the various instruments are to root surfaces; the conclusions were the same as for the first two aims, namely that there was no difference between treatments. The generally preconceived idea that more dental tissue is removed by curettes or sickle scalers was therefore not supported.Thèse de doctorat en science dentaire (DENT 3) --UCL, 200

Loss of tooth substance during root planing with various periodontal instruments: an in vitro study.

Ultrasonic and power-driven instrumentation is gaining in significance as an acceptable alternative to manual periodontal root treatment. Some question whether they do not remove too much tooth substance. Various ultrasonic scalers, hand instruments and two power-driven systems were compared by assessing the loss of tooth substance due to root instrumentation. Quantitative analysis of this effect of the instruments used was performed on 20 freshly extracted, non-periodontally involved, large human molars. In the first study, 40 specimens were randomly assigned to four groups of treatment: combined use of ultrasonic scaler and Periopolisher diamond-coated inserts (US-POL), hand instruments (MANUAL), Perioplaner-Periopolisher system (PPL-POL) and Periokit ultrasonic-designed scalers (PERIOKIT). The second study involved two treatment groups, ultrasonic scaler alone and hand instruments, each allocated with 20 teeth (small root fragments). An unpaired two-tailed t test was carried out for both studies to compare the average weight loss of root substance with the modes of instrumentation. The level of significance was set at p<or=0.05. The overall results of the first and second experimental trials did not reveal obvious differences in weight loss between the manual, ultrasonic or power-driven root treatments. Based on the results of these two comparative studies, the power-driven inserts or the various ultrasonic scalers tested did not remove more tooth substance than conventional hand instruments. They may thus be a useful alternative for the debridement of root surfaces