The RNA-binding protein PTBP1 is necessary for B cell selection in germinal centers.

Antibody affinity maturation occurs in germinal centers (GCs), where B cells cycle between the light zone (LZ) and the dark zone. In the LZ, GC B cells bearing immunoglobulins with the highest affinity for antigen receive positive selection signals from helper T cells, which promotes their rapid proliferation. Here we found that the RNA-binding protein PTBP1 was needed for the progression of GC B cells through late S phase of the cell cycle and for affinity maturation. PTBP1 was required for proper expression of the c-MYC-dependent gene program induced in GC B cells receiving T cell help and directly regulated the alternative splicing and abundance of transcripts that are increased during positive selection to promote proliferation

Repair of polychromatic radiation induced DNA damage in the archaeon Halobacterium salinarum NRC-1

Solar ultraviolet (UV) radiation has mutagenic and often lethal effects on all living organisms. However, there are extremophiles such as the halophilic model archaeon Halobacterium (Hbt.) salinarum NRC-1 that developed high resistance against this kind of stress, which is primarily due to efficient DNA repair systems. These systems include the light-dependent repair mechanism photoreactivation, which allows the direct reversal of pyrimidine dimer formation and the light-independent nucleotide-excision repair (NER) mechanism. Hbt. salinarum NRC-1 thrives in high-salt environments such as solar salterns or ancient halite. With regards to the recent discovery of liquid water in form of high-saline brines on Mars, investigations on the viability and adaptability of Hbt. salinarum NRC-1 to space- and Mars relevant parameters such as non-ionizing UV radiation becomes more interesting for astrobiological research. While it is already well known that these extremophiles are capable of repairing DNA damage after exposure to UV radiation, the main focus of this work lies in the investigation of whether Hbt. salinarum NRC-1 is also able to actively repair UV radiation induced DNA damage during irradiation. Enzymatic activity is generally reduced at lower temperatures. Therefore we first examined the survivability of Hbt. salinarum NRC-1 following exposure to simulated solar radiation at 4°C and 37°C. As a means of comparison, we determined the amount of general DNA damage induced by UV radiation using RAPD-PCR and qPCR. Furthermore, we analyzed the regulation of repair genes, such as the photolyase, during irradiation by qRT-PCR. Our results demonstrate that the survival of Hbt. salinarum NRC-1 is better when exposed to solar radiation at 37°C compared to 4°C. This correlates with less UV radiation induced DNA damage when irradiated at these temperatures. However, we did not observe an upregulation of the phr2 gene under these experimental conditions. To test the hypothesis that another protection mechanism is active at higher temperatures such as quenching of reactive oxygen species (ROS) by bacterioruberin, we analyzed the production of ROS during exposure. Nonetheless, this hypothesis could not be confirmed in these experiments, which is why further investigations are necessary to provide greater insight into how Hbt. salinarum NRC-1 manages to survive in its extreme environments and how they were able to adapt to hostile conditions. This would help understanding the basic conditions and limitations for the evolution and distribution of life

The RNA-binding protein PTBP1 is necessary for B cell selection in germinal centers.

Antibody affinity maturation occurs in germinal centers (GCs), where B cells cycle between the light zone (LZ) and the dark zone. In the LZ, GC B cells bearing immunoglobulins with the highest affinity for antigen receive positive selection signals from helper T cells, which promotes their rapid proliferation. Here we found that the RNA-binding protein PTBP1 was needed for the progression of GC B cells through late S phase of the cell cycle and for affinity maturation. PTBP1 was required for proper expression of the c-MYC-dependent gene program induced in GC B cells receiving T cell help and directly regulated the alternative splicing and abundance of transcripts that are increased during positive selection to promote proliferation

Resistance of the Archaeon Halococcus morrhuae and the Biofilm‐Forming Bacterium Halomonas muralis to Exposure to Low Earth Orbit for 534 Days

The halophilic archaeon Halococcus morrhuae and the biofilm‐forming bacterium Halomonas muralis were exposed to space conditions during the EXPOSE‐R2 mission. Evidence for both strains co‐existing on a mural in the castle Herberstein (Austria) has been found and here we tested the theory that the biofilm produced by Hlm. muralis may act as a protective layer for Hcc. morrhuae during exposure to extreme conditions. During Pre‐flight tests it was shown that Hcc. morrhuae is significantly more resistant to extreme conditions compared to Hlm. muralis. A mixture of both strains proved advantageous only for the survival of Hcc. morrhuae. Hcc. morrhuae was exposed independently and in combination with Hlm. muralis to space conditions outside of the International Space Station (ISS) for 534 days. Survival of Hcc. morrhuae was investigated by most probable number test and colony‐forming unit assay; damage inflicted to genomic DNA was evaluated by random amplified polymorphic DNA‐PCR and the integrity of the 16S rRNA by real‐time PCR. Exposure to extreme conditions on Earth as well as in outer space had a strong detrimental effect on the survival and genomic stability of Hcc. morrhuae; however, we were able to re‐cultivate Hcc. morrhuae from samples exposed outside of the ISS

Targeting the Hedgehog pathway in combination with X-ray or carbon ion radiation decreases migration of MCF-7 breast cancer cells

The use of carbon ion therapy for cancer treatment is becoming more widespread due to the advantages of carbon ions compared with X‑rays. Breast cancer patients may benefit from these advantages, as the surrounding healthy tissues receive a lower dose, and the increased biological effectiveness of carbon ions can better control radioresistant cancer cells. Accumulating evidence indicates that the Hedgehog (Hh) pathway is linked to the development and progression of breast cancer, as well as to resistance to X‑irradiation and the migratory capacity of cancer cells. Hence, there is an increasing interest in targeting the Hh pathway in combination with radiotherapy. Several studies have already investigated this treatment strategy with conventional radiotherapy. However, to the best of our knowledge, the combination of Hh inhibitors with particle therapy has not yet been explored. The aim of the present study was to investigate the potential of the Hh inhibitor GANT61 as an effective modulator of radiosensitivity and migration potential in MCF‑7 breast cancer cells, and compare potential differences between carbon ion irradiation and X‑ray exposure. Although Hh targeting was not able to radiosensitise cells to any radiation type used, the combination of GANT61 with X‑rays or carbon ions (energy: 95 MeV/n; linear energy transfer: 73 keV/µm) was more effective in decreasing MCF‑7 cell migration compared with either radiation type alone. Gene expression of the Hh pathway was affected to different degrees in response to X‑ray and carbon ion irradiation, as well as in response to the combination of GANT61 with irradiation. In conclusion, combining Hh inhibition with radiation (X‑rays or carbon ions) more effectively decreased breast cancer cell migration compared with radiation treatment alone.status: publishe

Sphagnum farming in a eutrophic world: The importance of optimal nutrient stoichiometry

Large areas of peatlands have worldwide been drained to facilitate agriculture, which has adverse effects on the environment and the global climate. Agriculture on rewetted peatlands (paludiculture) provides a sustainable alternative to drainage-based agriculture. One form of paludiculture is the cultivation of Sphagnum moss, which can be used as a raw material for horticultural growing media. Under natural conditions, most Sphagnum mosses eligible for paludiculture typically predominate only in nutrient-poor wetland habitats. It is unknown, however, how the prevailing high nutrient levels in rewetted agricultural peatlands interfere with optimal Sphagnum production. We therefore studied the effect of enriched nutrient conditions remaining even after top soil removal and further caused by external supply of nutrient-rich irrigation water and (generally) high inputs of atmospheric nitrogen (N) to habitat biogeochemistry, biomass production and nutrient stoichiometry of introduced Sphagnum palustre and S. papillosum in a rewetted peatland, which was formerly in intensive agricultural use. Airborne N was responsible for the major supply of N. Phosphorus (P) and potassium (K) were mainly supplied by irrigation water. The prevailing high nutrient levels (P and K) are a result of nutrient-rich irrigation water from the surroundings. Peat porewater (10 cm below peatmoss surface) CO2 concentrations were high, bicarbonate concentrations low, and the pH was around 4.2. Provided that moisture supply is sufficient and dominance of fast-growing, larger graminoids suppressed (in order to avoid outshading of Sphagnum mosses), strikingly very high biomass yields of 6.7 and 6.5 t DW ha(-1) yr(-1) (S, palustre and S. papillosum [including S. fallax biomass], respectively) were obtained despite high N supply and biomass N concentrations. Despite high P and K supply and uptake, N:P and N:K ratios in the Sphagnum capitula were still low. Sphagnum mosses achieved high nutrient sequestration rates of 34 kg N, 17 kg K and 4 kg P ha(-1) yr(-1) from May 2013 to May 2014, which shows that the site acted as an active nutrient sink. Nutrient management still needs further improvement to reduce the competitive advantage of fast growing peatmoss species (cf. S. fallax) at the expense of slower growing but preferred peatmosses as horticultural substrate (S. palustre and S. papillosum) to optimize the quality of biomass yields. In conclusion, Sphagnum farming is well able to thrive under high N input provided that there is a simultaneous high input of P and K from irrigation water, which facilitates high production rates. Due to the lack of suitable, nutrient poor sites, it seems to be useful to remove the topsoil (mainly P removal) prior to start growing Sphagnum mosses. In addition, bicarbonate concentrations have to stay sufficientlylow to ensure a low pH, CO2 supply from the peat soil should be sufficiently high to prevent C limitation, and graminoids should be mown regularly. (C) 2016 Elsevier B.V. All rights reserved

Nutrient dynamics of Sphagnum farming on rewetted bog grassland in NW Germany

The agricultural use of drained peatlands leads to huge emissions of greenhouse gases and nutrients. A land-use alternative that allows rewetting of drained peatland while maintaining agricultural production is the cultivation of Sphagnum biomass as a renewable substitute for fossil peat in horticultural growing media (Sphagnum farming). We studied Sphagnum productivity and nutrient dynamics during two years in two Sphagnum farming sites in NW Germany, which were established on drained bog grassland by sod removal, rewetting, and the introduction of Sphagnum fragments in 2011 and 2016, respectively. We found a considerable and homogeneous production of Sphagnum biomass (>3.6 ton DW ha‐−1 yr−1), attributable to the high nutrient levels, low alkalinity, and even distribution of the irrigation water. The ammonium legacy from former drainage-based agriculture rapidly declined after rewetting, while nutrient mobilization was negligible. CH4 concentrations in the rewetted soil quickly decreased to very low levels. The Sphagnum biomass sequestered high loads of nutrients (46.0 and 47.4 kg N, 3.9 and 4.9 kg P, and 9.8 and 16.1 kg K ha−1 yr−1 in the 7.5 y and 2.5 y old sites, respectively), preventing off-site eutrophication. We conclude that Sphagnum farming as an alternative for drainage-based peatland agriculture may contribute effectively to tackling environmental challenges such as local and regional downstream pollution and global climate change

A naturally occurring polyacetylene isolated from carrots promotes health and delays signatures of aging

To ameliorate or even prevent signatures of aging in ultimately humans, we here report the identification of a previously undescribed polyacetylene contained in the root of carrots (Daucus carota), hereafter named isofalcarintriol, which we reveal as potent promoter of longevity in the nematode C. elegans. We assign the absolute configuration of the compound as (3 S,8 R,9 R,E)-heptadeca-10-en-4,6-diyne-3,8,9-triol, and develop a modular asymmetric synthesis route for all E-isofalcarintriol stereoisomers. At the molecular level, isofalcarintriol affects cellular respiration in mammalian cells, C. elegans, and mice, and interacts with the α-subunit of the mitochondrial ATP synthase to promote mitochondrial biogenesis. Phenotypically, this also results in decreased mammalian cancer cell growth, as well as improved motility and stress resistance in C. elegans, paralleled by reduced protein accumulation in nematodal models of neurodegeneration. In addition, isofalcarintriol supplementation to both wild-type C57BL/6NRj mice on high-fat diet, and aged mice on chow diet results in improved glucose metabolism, increased exercise endurance, and attenuated parameters of frailty at an advanced age. Given these diverse effects on health parameters in both nematodes and mice, isofalcarintriol might become a promising mitohormesis-inducing compound to delay, ameliorate, or prevent aging-associated diseases in humans.ISSN:2041-172

Nutrient dynamics of Sphagnum farming on rewetted bog grassland in NW Germany

The agricultural use of drained peatlands leads to huge emissions of greenhouse gases and nutrients. A land-use alternative that allows rewetting of drained peatland while maintaining agricultural production is the cultivation of Sphagnum biomass as a renewable substitute for fossil peat in horticultural growing media (Sphagnum farming). We studied Sphagnum productivity and nutrient dynamics during two years in two Sphagnum farming sites in NW Germany, which were established on drained bog grassland by sod removal, rewetting, and the introduction of Sphagnum fragments in 2011 and 2016, respectively. We found a considerable and homogeneous production of Sphagnum biomass (>3.6 ton DW ha‐−1 yr−1), attributable to the high nutrient levels, low alkalinity, and even distribution of the irrigation water. The ammonium legacy from former drainage-based agriculture rapidly declined after rewetting, while nutrient mobilization was negligible. CH4 concentrations in the rewetted soil quickly decreased to very low levels. The Sphagnum biomass sequestered high loads of nutrients (46.0 and 47.4 kg N, 3.9 and 4.9 kg P, and 9.8 and 16.1 kg K ha−1 yr−1 in the 7.5 y and 2.5 y old sites, respectively), preventing off-site eutrophication. We conclude that Sphagnum farming as an alternative for drainage-based peatland agriculture may contribute effectively to tackling environmental challenges such as local and regional downstream pollution and global climate change

Nutrient dynamics of Sphagnum farming on rewetted bog grassland in NW Germany

The agricultural use of drained peatlands leads to huge emissions of greenhouse gases and nutrients. A land-use alternative that allows rewetting of drained peatland while maintaining agricultural production is the cultivation of Sphagnum biomass as a renewable substitute for fossil peat in horticultural growing media (Sphagnum farming). We studied Sphagnum productivity and nutrient dynamics during two years in two Sphagnum farming sites in NW Germany, which were established on drained bog grassland by sod removal, rewetting, and the introduction of Sphagnum fragments in 2011 and 2016, respectively. We found a considerable and homogeneous production of Sphagnum biomass (>3.6 ton DW ha- −1 yr−1), attributable to the high nutrient levels, low alkalinity, and even distribution of the irrigation water. The ammonium legacy from former drainage-based agriculture rapidly declined after rewetting, while nutrient mobilization was negligible. CH4 concentrations in the rewetted soil quickly decreased to very low levels. The Sphagnum biomass sequestered high loads of nutrients (46.0 and 47.4 kg N, 3.9 and 4.9 kg P, and 9.8 and 16.1 kg K ha− 1 yr− 1 in the 7.5 y and 2.5 y old sites, respectively), preventing off-site eutrophication. We conclude that Sphagnum farming as an alternative for drainage-based peatland agriculture may contribute effectively to tackling environmental challenges such as local and regional downstream pollution and global climate change