Membrane permeability selection drove the stereochemistry of life

Early in the evolution of life a proto-metabolic network was encapsulated within a membrane compartment. The permeability characteristics of the membrane determined several key functions of this network by determining which compounds could enter the compartment and which compounds could not. One key feature of known life is the utilisation of right-handed D- ribose and deoxyribose sugars and left-handed L- amino acid stereochemical isomers (enantiomers), however, it is not clear why life adopted this specific chirality. We previously demonstrated that an archaeal and an intermediate membrane mimic, bearing a mixture of bacterial and archaeal lipid characteristics (a ‘hybrid’ membrane), display increased permeability compared to bacterial-like membranes. Here, we investigate if these membranes can drive stereochemical selection on pentose sugars, hexose sugars and amino acids. Using permeability assays of homogenous unilamellar vesicles, we demonstrate that both membranes select for D- ribose and deoxyribose sugars while the hybrid membrane uniquely selects for a reduced alphabet of L- facing amino acids. This repertoire includes alanine, the plausible first L- amino acid utilised. We conclude such compartments could provide stereochemical compound selection thereby demonstrating a solution to the chirality problem during the evolution of life

Bacteriostatic antibiotics promote CRISPR-Cas adaptive immunity by enabling increased spacer acquisition

This is the final version. Available on open access from Cell Press via the DOI in this recordData and code availability: Source data are available at Mendeley Data: https://doi.org/10.17632/gbdfwg325y.1 This paper does not report original code. Any additional information required to reanalyse the data reported in this paper is available from the lead contact upon request.Phages impose strong selection on bacteria to evolve resistance against viral predation. Bacteria can rapidly evolve phage resistance via receptor mutation or using their CRISPR-Cas adaptive immune systems. Acquisition of CRISPR immunity relies on the insertion of a phage-derived sequence into CRISPR arrays in the bacterial genome. Using Pseudomonas aeruginosa and its phage DMS3vir as a model, we demonstrate that conditions that reduce bacterial growth rates, such as exposure to bacteriostatic antibiotics (which inhibit cell growth without killing), promote the evolution of CRISPR immunity. We demonstrate that this is due to slower phage development under these conditions, which provides more time for cells to acquire phage-derived sequences and mount an immune response. Our data reveal that the speed of phage development is a key determinant of the evolution of CRISPR immunity and suggest that use of bacteriostatic antibiotics can trigger elevated levels of CRISPR immunity in human-associated and natural environments.European Union Horizon 2020Natural Environment Research Council (NERC)Ministry of Science and Higher Education of the Russian FederationNational Institutes of Health (NIH)Russian Science Foundatio

Heterologous Protein Expression Favors the Formation of Protein Aggregates in Persister and Viable but Nonculturable Bacteria

This is the final version. Available from the American Chemical Society via the DOI in this record. Environmental and intracellular stresses can perturb protein homeostasis and trigger the formation and accumulation of protein aggregates. It has been recently suggested that the level of protein aggregates accumulated in bacteria correlates with the frequency of persister and viable but nonculturable cells that transiently survive treatment with multiple antibiotics. However, these findings have often been obtained employing fluorescent reporter strains. This enforced heterologous protein expression facilitates the visualization of protein aggregates but could also trigger the formation and accumulation of protein aggregates. Using microfluidics-based single-cell microscopy and a library of green fluorescent protein reporter strains, we show that heterologous protein expression favors the formation of protein aggregates. We found that persister and viable but nonculturable bacteria surviving treatment with antibiotics are more likely to contain protein aggregates and downregulate the expression of heterologous proteins. Our data also suggest that such aggregates are more basic with respect to the rest of the cell. These findings provide evidence for a strong link between heterologous protein expression, protein aggregation, intracellular pH, and phenotypic survival to antibiotics, suggesting that antibiotic treatments against persister and viable but nonculturable cells could be developed by modulating protein aggregation and pH regulation.The Royal SocietyMarie Skłodowska‐CurieBiotechnology and Biological Sciences Research Council (BBSRC)Medical Research Council (MRC)The Gordon and Betty Moore FoundationMedical Research Council (MRC)Engineering and Physical Sciences Research Council (EPSRC)University of ExeterDST

Over 200,000 kilometers of free-flowing river habitat in Europe is altered due to impoundments

European rivers are disconnected by more than one million man-made barriers that physically limit aquatic species migration and contribute to modification of freshwater habitats. Here, a Conceptual Habitat Alteration Model for Ponding is developed to aid in evaluating the effects of impoundments on fish habitats. Fish communities present in rivers with low human impact and their broad environmental settings enable classification of European rivers into 15 macrohabitat types. These classifications, together with the estimated fish sensitivity to alteration of their habitat are used for assessing the impacts of six main barrier types (dams, weirs, sluices, culverts, fords, and ramps). Our results indicate that over 200,000 km or 10% of previously free-flowing river habitat has been altered due to impoundments. Although they appear less frequently, dams, weirs and sluices cause much more habitat alteration than the other types. Their impact is regionally diverse, which is a function of barrier height, type and density, as well as biogeographical location. This work allows us to foresee what potential environmental gain or loss can be expected with planned barrier management actions in rivers, and to prioritize management actions

Detection and localization of early- and late-stage cancers using platelet RNA

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening

Global survival trends for brain tumors, by histology: analysis of individual records for 556,237 adults diagnosed in 59 countries during 2000–2014 (CONCORD-3)

Background: Survival is a key metric of the effectiveness of a health system in managing cancer. We set out to provide a comprehensive examination of worldwide variation and trends in survival from brain tumors in adults, by histology. Methods: We analyzed individual data for adults (15–99 years) diagnosed with a brain tumor (ICD-O-3 topography code C71) during 2000–2014, regardless of tumor behavior. Data underwent a 3-phase quality control as part of CONCORD-3. We estimated net survival for 11 histology groups, using the unbiased nonparametric Pohar Perme estimator. Results: The study included 556,237 adults. In 2010–2014, the global range in age-standardized 5-year net survival for the most common sub-types was broad: in the range 20%–38% for diffuse and anaplastic astrocytoma, from 4% to 17% for glioblastoma, and between 32% and 69% for oligodendroglioma. For patients with glioblastoma, the largest gains in survival occurred between 2000–2004 and 2005–2009. These improvements were more noticeable among adults diagnosed aged 40–70 years than among younger adults. Conclusions: To the best of our knowledge, this study provides the largest account to date of global trends in population-based survival for brain tumors by histology in adults. We have highlighted remarkable gains in 5-year survival from glioblastoma since 2005, providing large-scale empirical evidence on the uptake of chemoradiation at population level. Worldwide, survival improvements have been extensive, but some countries still lag behind. Our findings may help clinicians involved in national and international tumor pathway boards to promote initiatives aimed at more extensive implementation of clinical guidelines

Worldwide trends in population-based survival for children, adolescents, and young adults diagnosed with leukaemia, by subtype, during 2000–14 (CONCORD-3) : analysis of individual data from 258 cancer registries in 61 countries

Background Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0–14 years) and adults (aged 15–99 years) diagnosed with a haematological malignancy during 2000–14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0–24 years). Methods We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0–14 years), adolescents (15–19 years), and young adults (20–24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. Findings 164563 young people were included in this analysis: 121328 (73·7%) children, 22963 (14·0%) adolescents, and 20272 (12·3%) young adults. In 2010–14, the most common subtypes were lymphoid leukaemia (28205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010–14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000–14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. Interpretation This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group.peer-reviewe

Concentration of biogenic compounds in sewage sludge and reject waters produced in the municipal wastewater treatment plants (Łomazy and Sławatycze)

Osady ściekowe wytwarzane w gminnych oczyszczalniach ścieków charakteryzują się wysoką wilgotnością, a ich jakość zależy od typu oczyszczalni. W ramach przeprowadzonych badań analizowano skład chemiczny nieustabilizowanych osadów i wód odciekowych powstających w dwóch wiejskich oczyszczalniach ścieków o przepustowości 300 m3/dobę, różniących się typem reaktora biochemicznego. Niezależnie od typu oczyszczalni, stężenie węgla organicznego, azotu organicznego i fosforu ogólnego w suchej masie osadów było na podobnym poziomie. Odnotowano statystycznie istotne różnice w kwasowości osadów oraz w zawartości suchej masy w osadach. Także w wodach odciekowych powstających z osadów ściekowych odnotowano statystycznie istotne różnice w stężeniach azotanów i fosforanów. Ustalono, że azot w nieustabilizowanych osadach ściekowych występuje głównie w formie organicznej. Wysoka wilgotność osadów ściekowych, ich kwaśny odczyn oraz wysokie stężenie azotu w wodach odciekowych w formie nieorganicznych połączeń wymagają bezpiecznej, z punktu widzenia ochrony środowiska, gospodarki osadami. Wyniki analizy statystycznej badanych próbek osadów pozwoliły na ocenę stabilności pracy oczyszczalni.Sewage sludge produced in municipal wastewater treatment plants is characterized by high moisture, while its quality depends on the type of treatment plant. Municipal sewage sludge is considered to be a waste and a strong emphasis is put on managing waste in a way not posing a threat to the environment. In this study, chemical composition of unsettled sludge and reject waters produced in two municipal wastewater treatment plants, both operating at a throughput of up to 300 m3/day, was analysed. The two plants, treating only municipal sewage, differed in the type of biochemical reactor. They are located in the area of Lublin voivodeship. Research showed that the sludge from both plants had an acidic reaction and contained more than 90% of water. Depending on the plant where the sludge was produced, the samples differed in pH values and the level of hydration. The concentration of organic matter, organic nitrogen and total phosphorus in the dry weight were alike in the samples taken from the two plants. On a dry weight basis, sewage sludge contained on average about 80% organic matter, more than 5% nitrogen and about 2% phosphorus. On the basis of calculated C/N ratio of the dry weight it was established that using the studied wastewater sludge in agriculture would be the most sustainable method of its management. The reject waters samples collected from the two wastewater treatment plants varied in the concentrations of ammonium, nitrate and phosphorus ions. Ammonium ions concentrations were the highest in the reject waters. The differences in nitrate and phosphorus concentrations noted in the samples collected from the two plants were statistically significant. All the aspects such as high moisture of sewage sludge, its acidic reaction and high nitrogen concentration in reject waters occurring in the form of inorganic compounds require appropriate methods of waste management safe for the environment. The results of the statistical analysis of the studied sludge samples allowed for the assessment of the reliability of the two wastewater treatment plants