Give CRISPR a chance : the GeneSprout Initiative

Did you know that a group of early-career researchers launched an initiative enabling open dialog on new plant breeding techniques, such as genome editing? We developed a wide-ranging initiative that aims to facilitate public engagement and provide a platform for young plant scientists to encourage participation in science communication

Conceptual design of the early implementation of the NEutron Detector Array (NEDA) with AGATA

The NEutron Detector Array (NEDA) project aims at the construction of a new high-efficiency compact neutron detector array to be coupled with large (Formula presented.) -ray arrays such as AGATA. The application of NEDA ranges from its use as selective neutron multiplicity filter for fusion-evaporation reaction to a large solid angle neutron tagging device. In the present work, possible configurations for the NEDA coupled with the Neutron Wall for the early implementation with AGATA has been simulated, using Monte Carlo techniques, in order to evaluate their performance figures. The goal of this early NEDA implementation is to improve, with respect to previous instruments, efficiency and capability to select multiplicity for fusion-evaporation reaction channels in which 1, 2 or 3 neutrons are emitted. Each NEDA detector unit has the shape of a regular hexagonal prism with a volume of about 3.23l and it is filled with the EJ301 liquid scintillator, that presents good neutron- (Formula presented.) discrimination properties. The simulations have been performed using a fusion-evaporation event generator that has been validated with a set of experimental data obtained in the 58Ni + 56Fe reaction measured with the Neutron Wall detector array

Conceptual Design of a Novel Small-Scale CO2 Compressor: Based on Gas Bearing Technology

In conventional compressor technology, high pressure ratios are often achieved by multiple, successive compression stages. This is done to avoid high temperatures due to the adiabatic nature of most compression processes which deteriorates the working of oil lubrication. The aim of this work is to reduce a conventional four-stage system to only two stages as this may improve the size and expenses of the system. This goal combined with a long desired lifetime, makes that a compressor is developed that operates based on gas bearing technology.The design is focused on two main subjects. Firstly, the load capacity of the gas bearings is significantly lower than oil lubricated bearings due to the reduced viscosity. To avoid mechanical contact and wear of the components this has been thoroughly analysed using finite element methods. The oscillating nature of the loads in the system enhances the squeeze effect from the Reynolds equation. Secondly, the sealing function of gas bearings opposing internal leakage is evaluated carefully to obtain a desired efficiency. Based on these simulations, the mechanical design of the compressor is optimized to improve the manufacturing of the compressor components

Identification and Expression Analysis of the Genes Involved in the Raffinose Family Oligosaccharides Pathway of Phaseolus vulgaris and Glycine max

Raffinose family oligosaccharides (RFO) play an important role in plants but are also considered to be antinutritional factors. A profound understanding of the galactinol and RFO biosynthetic gene families and the expression patterns of the individual genes is a prerequisite for the sustainable reduction of the RFO content in the seeds, without compromising normal plant development and functioning. In this paper, an overview of the annotation and genetic structure of all galactinol- and RFO biosynthesis genes is given for soybean and common bean. In common bean, three galactinol synthase genes, two raffinose synthase genes and one stachyose synthase gene were identified for the first time. To discover the expression patterns of these genes in different tissues, two expression atlases have been created through re-analysis of publicly available RNA-seq data. De novo expression analysis through an RNA-seq study during seed development of three varieties of common bean gave more insight into the expression patterns of these genes during the seed development. The results of the expression analysis suggest that different classes of galactinol- and RFO synthase genes have tissue-specific expression patterns in soybean and common bean. With the obtained knowledge, important galactinol- and RFO synthase genes that specifically play a key role in the accumulation of RFOs in the seeds are identified. These candidate genes may play a pivotal role in reducing the RFO content in the seeds of important legumes which could improve the nutritional quality of these beans and would solve the discomforts associated with their consumption

Transcriptome-Guided Identification of Pectin Methyl-Esterase-Related Enzymes and Novel Molecular Processes Effectuating the Hard-to-Cook Defect in Common Bean (Phaseolus vulgaris L.)

The hard-to-cook defect in common beans is dictated by the ability to achieve cell separation during cooking. Hydrolysis of pectin methyl-esters by the pectin methyl-esterase (PME) enzyme influences cell separation. However, the contributions of the PME enzyme and the cell wall to the hard-to-cook defect have not been studied using molecular tools. We compared relevant molecular processes in fast- and slow-cooking bean varieties to understand the mechanisms underpinning the hard-to-cook defect. A PME spectrophotometric assay showed minor differences in enzyme activity between varieties. Meanwhile, a PME HMMER search in the P. vulgaris genome unveiled 113 genes encoding PMEs and PME inhibitors (PMEIs). Through RNA sequencing, we compared the gene expression of the PME-related genes in both varieties during seed development. A PME (Phvul010g080300) and PMEI gene (Phvul005g007600) showed the highest expression in the fast- and slow-cooking beans, respectively. We further identified 2132 differentially expressed genes (DEGs). Genes encoding cell-wall-related enzymes, mainly glycosylphosphatidylinositol mannosyltransferase, xyloglucan O-acetyltransferase, pectinesterase, and callose synthase, ranked among the top DEGs, indicating novel relations to the hard-to-cook defect. Gene ontology mapping revealed hydrolase activity and protein phosphorylation as functional categories with the most abundant upregulated DEGs in the slow-cooking bean. Additionally, the cell periphery contained 8% of the DEGs upregulated in the slow-cooking bean. This study provides new insights into the role of pectin methyl-esterase-related genes and novel cell wall processes in the occurrence of the hard-to-cook defect

PD-L1 blockade engages tumor-infiltrating lymphocytes to co-express targetable activating and inhibitory receptors

Background: The clinical benefit of immunotherapeutic approaches against cancer has been well established although complete responses are only observed in a minority of patients. Combination immunotherapy offers an attractive avenue to develop more effective cancer therapies by improving the efficacy and duration of the tumor-specific T-cell response. Here, we aimed at deciphering the mechanisms governing the response to PD-1/PD-L1 checkpoint blockade to support the rational design of combination immunotherapy. Methods: Mice bearing subcutaneous MC-38 tumors were treated with blocking PD-L1 antibodies. To establish high-dimensional immune signatures of immunotherapy-specific responses, the tumor microenvironment was analyzed by CyTOF mass cytometry using 38 cellular markers. Findings were further examined and validated by flow cytometry and by functional in vivo experiments. Immune profiling was extended to the tumor microenvironment of colorectal cancer patients. Results: PD-L1 blockade induced selectively the expansion of tumor-infiltrating CD4+ and CD8+ T-cell subsets, co-expressing both activating (ICOS) and inhibitory (LAG-3, PD-1) molecules. By therapeutically co-targeting these molecules on the TAI cell subsets in vivo by agonistic and antagonist antibodies, we were able to enhance PD-L1 blockade therapy as evidenced by an increased number of TAI cells within the tumor micro-environment and improved tumor protection. Moreover, TAI cells were also found in the tumor-microenvironment of colorectal cancer patients. Conclusions: This study shows the presence of T cell subsets in the tumor micro-environment expressing both activating and inhibitory receptors. These TAI cells can be targeted by combined immunotherapy leading to improved survival.</p

PD-L1 blockade engages tumor-infiltrating lymphocytes to co-express targetable activating and inhibitory receptors

Background: The clinical benefit of immunotherapeutic approaches against cancer has been well established although complete responses are only observed in a minority of patients. Combination immunotherapy offers an attractive avenue to develop more effective cancer therapies by improving the efficacy and duration of the tumor-specific T-cell response. Here, we aimed at deciphering the mechanisms governing the response to PD-1/PD-L1 checkpoint blockade to support the rational design of combination immunotherapy. Methods: Mice bearing subcutaneous MC-38 tumors were treated with blocking PD-L1 antibodies. To establish high-dimensional immune signatures of immunotherapy-specific responses, the tumor microenvironment was analyzed by CyTOF mass cytometry using 38 cellular markers. Findings were further examined and validated by flow cytometry and by functional in vivo experiments. Immune profiling was extended to the tumor microenvironment of colorectal cancer patients. Results: PD-L1 blockade induced selectively the expansion of tumor-infiltrating CD4+ and CD8+ T-cell subsets, co-expressing both activating (ICOS) and inhibitory (LAG-3, PD-1) molecules. By therapeutically co-targeting these molecules on the TAI cell subsets in vivo by agonistic and antagonist antibodies, we were able to enhance PD-L1 blockade therapy as evidenced by an increased number of TAI cells within the tumor micro-environment and improved tumor protection. Moreover, TAI cells were also found in the tumor-microenvironment of colorectal cancer patients. Conclusions: This study shows the presence of T cell subsets in the tumor micro-environment expressing both activating and inhibitory receptors. These TAI cells can be targeted by combined immunotherapy leading to improved survival.Comp Graphics & Visualisatio

Intercostal nerve implants transduced with an adenoviral vector encoding neurotrophin-3 promote regrowth of injured rat corticospinal tract fibers and improve hindlimb function

Following injury to central nervous tissues, damaged neurons are unable to regenerate their axons spontaneously. Implantation of peripheral nerves into the CNS, however, does result in axonal regeneration into these transplants and is one of the most powerful strategies to promote CNS regeneration. In the present study implantation of peripheral nerve bridges following dorsal hemisection is combined with ex vivo gene transfer with adenoviral vectors encoding neurotrophin-3 (Ad-NT-3) to examine whether this would stimulate regeneration of one of the long descending tracts of the spinal cord, the corticospinal tract (CST), into and beyond the peripheral nerve implant. We chose to use an adenoviral vector encoding NT-3 because CST axons are sensitive to this neurotrophin and Schwann cells in peripheral nerve implants do not express this neurotrophin. At 16 weeks postimplantation of Ad-NT-3-transduced intercostal nerves, approximately three- to fourfold more of the anterogradely traced corticospinal tract fibers had regrown their axons through gray matter below the lesion site when compared to control animals. Regrowth of CST fibers occurred over more than 8 mm distal to the lesion site. No regenerating CST fibers were, however, observed into the transduced peripheral implant. Animals with a peripheral nerve transduced with Ad-NT-3 also exhibited improved function of the hindlimbs when compared to control animals treated with an adenoviral vector encoding LacZ. Thus, transient overexpression of NT-3 in peripheral nerve tissue bridges is apparently sufficient to stimulate regrowth of CST fibers and to promote recovery of hindlimb function, but does not result in regeneration of CST fibers into such transplants. Taken together, combining an established neuro- transplantation approach with viral vector-gene transfer promotes the regrowth of injured CST fibers through gray matter and improves the recovery of hindlimb function. (C) 2000 Academic Press

Hysteroscopy before in-vitro fertilisation (inSIGHT) : A multicentre, randomised controlled trial

BACKGROUND: Hysteroscopy is often done in infertile women starting in-vitro fertilisation (IVF) to improve their chance of having a baby. However, no data are available from randomised controlled trials to support this practice. We aimed to assess whether routine hysteroscopy before the first IVF treatment cycle increases the rate of livebirths. METHODS: We did a pragmatic, multicentre, randomised controlled trial in seven university hospitals and 15 large general hospitals in the Netherlands. Women with a normal transvaginal ultrasound of the uterine cavity and no previous hysteroscopy who were scheduled for their first IVF treatment were randomly assigned (1:1) to either hysteroscopy with treatment of detected intracavitary abnormalities before starting IVF (hysteroscopy group) or immediate start of the IVF treatment (immediate IVF group). Randomisation was done with web-based concealed allocation and was stratified by centre with variable block sizes. Participants, doctors, and outcome assessors were not masked to the assigned group. The primary outcome was ongoing pregnancy (detection of a fetal heartbeat at >12 weeks of gestation) within 18 months of randomisation and resulting in livebirth. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01242852. FINDINGS: Between May 25, 2011, and Aug 27, 2013, we randomly assigned 750 women to receive either hysteroscopy (n=373) or immediate IVF (n=377). 209 (57%) of 369 women eligible for assessment in the hysteroscopy group and 200 (54%) of 373 in the immediate IVF group had a livebirth from a pregnancy during the trial period (relative risk 1·06, 95% CI 0·93-1·20; p=0·41). One (<1%) woman in the hysteroscopy group developed endometritis after hysteroscopy. INTERPRETATION: Routine hysteroscopy does not improve livebirth rates in infertile women with a normal transvaginal ultrasound of the uterine cavity scheduled for a first IVF treatment. Women with a normal transvaginal ultrasound should not be offered routine hysteroscopy. FUNDING: The Dutch Organisation for Health Research and Development (ZonMW)