Quantifying the Influence of Surface Texture and Shape on Structure from Motion 3D Reconstructions.

In general, optical methods for geometrical measurements are influenced by the surface properties of the examined object. In Structure from Motion (SfM), local variations in surface color or topography are necessary for detecting feature points for point-cloud triangulation. Thus, the level of contrast or texture is important for an accurate reconstruction. However, quantitative studies of the influence of surface texture on geometrical reconstruction are largely missing. This study tries to remedy that by investigating the influence of object texture levels on reconstruction accuracy using a set of reference artifacts. The artifacts are designed with well-defined surface geometries, and quantitative metrics are introduced to evaluate the lateral resolution, vertical geometric variation, and spatial-frequency information of the reconstructions. The influence of texture level is compared to variations in capturing range. For the SfM measurements, the ContextCapture software solution and a 50 Mpx DSLR camera are used. The findings are compared to results using calibrated optical microscopes. The results show that the proposed pipeline can be used for investigating the influence of texture on SfM reconstructions. The introduced metrics allow for a quantitative comparison of the reconstructions at varying texture levels and ranges. Both range and texture level are seen to affect the reconstructed geometries although in different ways. While an increase in range at a fixed focal length reduces the spatial resolution, an insufficient texture level causes an increased noise level and may introduce errors in the reconstruction. The artifacts are designed to be easily replicable, and by providing a step-by-step procedure of our testing and comparison methodology, we hope that other researchers will make use of the proposed testing pipeline.

Rough or Noisy? Metrics for Noise Estimation in SfM Reconstructions.

Structure from Motion (SfM) can produce highly detailed 3D reconstructions, but distinguishing real surface roughness from reconstruction noise and geometric inaccuracies has always been a difficult problem to solve. Existing SfM commercial solutions achieve noise removal by a combination of aggressive global smoothing and the reconstructed texture for smaller details, which is a subpar solution when the results are used for surface inspection. Other noise estimation and removal algorithms do not take advantage of all the additional data connected with SfM. We propose a number of geometrical and statistical metrics for noise assessment, based on both the reconstructed object and the capturing camera setup. We test the correlation of each of the metrics to the presence of noise on reconstructed surfaces and demonstrate that classical supervised learning methods, trained with these metrics can be used to distinguish between noise and roughness with an accuracy above 85%, with an additional 5-6% performance coming from the capturing setup metrics. Our proposed solution can easily be integrated into existing SfM workflows as it does not require more image data or additional sensors. Finally, as part of the testing we create an image dataset for SfM from a number of objects with varying shapes and sizes, which are available online together with ground truth annotations.

Globoids and Phytase: The Mineral Storage and Release System in Seeds.

Phytate and phytases in seeds are the subjects of numerous studies, dating back as far as the early 20th century. Most of these studies concern the anti-nutritional properties of phytate, and the prospect of alleviating the effects of phytate with phytase. As reasonable as this may be, it has led to a fragmentation of knowledge, which hampers the appreciation of the physiological system at hand. In this review, we integrate the existing knowledge on the chemistry and biosynthesis of phytate, the globoid cellular structure, and recent advances on plant phytases. We highlight that these components make up a system that serves to store and-in due time-release the seed's reserves of the mineral nutrients phosphorous, potassium, magnesium, and others, as well as inositol and protein. The central component of the system, the phytate anion, is inherently rich in phosphorous and inositol. The chemical properties of phytate enable it to sequester additional cationic nutrients. Compartmentalization and membrane transport processes regulate the buildup of phytate and its associated nutrients, resulting in globoid storage structures. We suggest, based on the current evidence, that the degradation of the globoid and the mobilization of the nutrients also depend on membrane transport processes, as well as the enzymatic action of phytase.

Lab-scale preparation and QC of phytase assay substrate from rice bran.

Phytases are involved in the phosphate acquisition and remobilization in plants, microbes and animals. They have become important technical enzymes in the feed industry and are used to make phosphate, present in animal feed as phytate, available for monogastric animal nutrition. Phytases may also be beneficial to human nutrition because phytate is known to interfere with the uptake of important micronutrients. Accordingly, phytases attract considerable research attention and phytate substrate lacking contaminants that interfere with commonly used phosphate-release assays is essential for this field of science. A procedure to prepare suitable sodium phytate from rice bran is presented. Extracted phytate is precipitated with barium hydroxide and re-dissolved in methanol after washing steps and sulphuric acid treatment. Remaining impurities are precipitated before the dissolved phytate is recovered as the sodium salt by addition of sodium hydroxide. In order to make the substrate widely available for research communities, the procedure relies solely on basic laboratory equipment and materials. Methods for quality control and monitoring of the purified sodium phytate or commercial alternatives are also presented.

68Ga-PSMA-PET/CT in comparison with 18F-fluoride-PET/CT and whole-body MRI for the detection of bone metastases in patients with prostate cancer: a prospective diagnostic accuracy study.

OBJECTIVES: To determine the diagnostic accuracy of 68gallium prostate-specific membrane antigen (PSMA)-based positron emission tomography/computed tomography (PET/CT) in comparison with 18F-fluoride-based PET/CT (NaF-PET/CT) and whole-body magnetic resonance imaging (WB-MRI) for the detection of bone metastases in patients with prostate cancer. METHODS: Sixty patients with prostate cancer were included in the period May 2016 to June 2017. The participants underwent three scans (index tests) within 30 days: a NaF-PET/CT, a WB-MRI and a PSMA-PET/CT. Experienced specialists assessed the scans. In the absence of a histological reference standard, the final diagnosis was determined as a panel diagnosis. Measures of the diagnostic performances of the index tests were calculated from patient-based dichotomous outcomes (0 or ≥ 1 bone metastasis) and pairwise compared (McNemar test). For each index test, the agreement with the final diagnosis with regard to the number of bone metastases detected (0, 1-5, > 5) and the inter-reader agreement was calculated (kappa coefficients). RESULTS: Fifty-five patients constituted the final study population; 20 patients (36%) were classified as having bone metastatic disease as their final diagnosis. The patient-based diagnostic performances were (sensitivity, specificity, overall accuracy) PSMA-PET/CT (100%, 100%, 100%), NaF-PET/CT (95%, 97%, 96%) and WB-MRI (80%, 83%, 82%). The overall accuracy of PSMA-PET/CT was significantly more favourable compared to WB-MRI (p = 0.004), but not to NaF-PET/CT (p = 0.48). PSMA-PET/CT classified the number of bone metastases reliably compared to the final diagnosis (kappa coefficient 0.97) and with an "almost perfect" inter-reader agreement (kappa coefficient 0.93). CONCLUSIONS: The overall accuracy of PSMA-PET/CT was significantly more advantageous compared to WB-MRI, but not to NaF-PET/CT. KEY POINTS: • PSMA-PET/CT assessed the presence of bone metastases correctly in all 55 patients • PSMA-PET/CT was more advantageous compared to WB-MRI • No difference was found between PSMA-PET/CT and NaF-PET/CT.

Molecular Advances on Phytases in Barley and Wheat.

Phytases are pro-nutritional enzymes that hydrolyze phytate and make associated nutrients, such as phosphorous, iron, and zinc, bioavailable. Single-stomached animals and humans depend on phytase supplied through the diet or the action of phytase on the food before ingestion. As a result, phytases-or lack thereof-have a profound impact on agricultural ecosystems, resource management, animal health, and public health. Wheat, barley and their Triticeae relatives make exceptionally good natural sources of phytase. This review highlights advances in the understanding of the molecular basis of the phytase activity in wheat and barley, which has taken place over the past decade. It is shown how the phytase activity in the mature grains of wheat and barley can be ascribed to the PAPhy_a gene, which exists as a single gene in barley and in two or three homeologous copies in tetra- and hexaploid wheat, respectively. It is discussed how understanding the function and regulation of PAPhy_a may support the development of improved wheat and barley with even higher phytase activity.

Barley HvPAPhy_a as transgene provides high and stable phytase activities in mature barley straw and in grains.

The phytase purple acid phosphatase (HvPAPhy_a) expressed during barley seed development was evaluated as transgene for overexpression in barley. The phytase was expressed constitutively driven by the cauliflower mosaic virus 35S-promoter, and the phytase activity was measured in the mature grains, the green leaves and in the dry mature vegetative plant parts left after harvest of the grains. The T2 -generation of HvPAPhy_a transformed barley showed phytase activity increases up to 19-fold (29 000 phytase units (FTU) per kg in mature grains). Moreover, also in green leaves and mature dry straw, phytase activities were increased significantly by 110-fold (52 000 FTU/kg) and 57-fold (51 000 FTU/kg), respectively. The HvPAPhy_a-transformed barley plants with high phytase activities possess triple potential utilities for the improvement of phosphate bioavailability. First of all, the utilization of the mature grains as feed to increase the release of bio-available phosphate and minerals bound to the phytate of the grains; secondly, the utilization of the powdered straw either directly or phytase extracted hereof as a supplement to high phytate feed or food; and finally, the use of the stubble to be ploughed into the soil for mobilizing phytate-bound phosphate for plant growth.

Optimized barley phytase gene expression by focused FIND-IT screening for mutations in cis-acting regulatory elements.

Introduction: Induced modification of plant gene expression is of both fundamental and applied importance. Cis-acting regulatory elements (CREs) are major determinants of the spatiotemporal strength of gene expression. Yet, there are few examples where induced genetic variation in predetermined CREs has been exploited to improve or investigate crop plants. Methods: The digital PCR based FIND-IT technology was applied to discover barley mutants with CRE variants in the promoter of the nutritional important barley grain phytase (PAPhy_a) gene. Results and discussion: Mutants with higher or lower gene expression and ultimately higher or lower mature grain phytase activity (MGPA), respectively, were discovered. Field trials and inositol phosphate profiling during germination showed that PAPhy_a does not influence agronomic performance under the trial conditions but it does shorten the lag time of phosphate mobilization during germination. Higher endogenous MGPA is an improvement of grain quality for feed use as it improves the phosphate bioavailability for monogastric animals. Moreover, as the targeted CRE motifs of the PAPhy_a promoter are shared with a range of seed expressed genes like key cereal and legume storage genes, the current results demonstrates a concept for modulating individual gene expression levels of a range of seed genes.

High mature grain phytase activity in the Triticeae has evolved by duplication followed by neofunctionalization of the purple acid phosphatase phytase (PAPhy) gene.

The phytase activity in food and feedstuffs is an important nutritional parameter. Members of the Triticeae tribe accumulate purple acid phosphatase phytases (PAPhy) during grain filling. This accumulation elevates mature grain phytase activities (MGPA) up to levels between ~650 FTU/kg for barley and 6000 FTU/kg for rye. This is notably more than other cereals. For instance, rice, maize, and oat have MGPAs below 100 FTU/kg. The cloning and characterization of the PAPhy gene complement from wheat, barley, rye, einkorn, and Aegilops tauschii is reported here. The Triticeae PAPhy genes generally consist of a set of paralogues, PAPhy_a and PAPhy_b, and have been mapped to Triticeae chromosomes 5 and 3, respectively. The promoters share a conserved core but the PAPhy_a promoter have acquired a novel cis-acting regulatory element for expression during grain filling while the PAPhy_b promoter has maintained the archaic function and drives expression during germination. Brachypodium is the only sequenced Poaceae sharing the PAPhy duplication. As for the Triticeae, the duplication is reflected in a high MGPA of ~4200 FTU/kg in Brachypodium. The sequence conservation of the paralogous loci on Brachypodium chromosomes 1 and 2 does not extend beyond the PAPhy gene. The results indicate that a single-gene segmental duplication may have enabled the evolution of high MGPA by creating functional redundancy of the parent PAPhy gene. This implies that similar MGPA levels may be out of reach in breeding programs for some Poaceae, e.g. maize and rice, whereas Triticeae breeders should focus on PAPhy_a.

Cisgenic barley with improved phytase activity.

The cisgenesis concept implies that plants are transformed only with their own genetic materials or genetic materials from closely related species capable of sexual hybridization. Furthermore, foreign sequences such as selection genes and vector-backbone sequences should be absent. We used a barley phytase gene (HvPAPhy_a) expressed during grain filling to evaluate the cisgenesis concept in barley. The marker gene elimination method was used to obtain marker-free plant lines. Here, the gene of interest and the selection gene are flanked by their own T-DNA borders to allow unlinked integration of the two genes. We analysed the transformants for co-transformation efficiency, increased phytase activities in the grain, integration of the kanamycin resistance gene of the vector-backbone and segregation between the HvPAPhy_a insert and the hygromycin resistance gene. The frequencies of the four parameters imply that it should be possible to select 11 potentially cisgenic T(1) -lines out of the 72 T(0) -lines obtained, indicating that the generation of cisgenic barley is possible at reasonable frequencies with present methods. We selected two potential cisgenic lines with a single extra copy of the HvPAPhy_a insert for further analysis. Seeds from plants homozygous for the insert showed 2.6- and 2.8-fold increases in phytase activities and the activity levels were stable over the three generations analysed. In one of the selected lines, the flanking sequences from both the left and right T-DNA borders were analysed. These sequences confirmed the absence of truncated vector-backbone sequences linked to the borders. The described line should therefore be classified as cisgenic.

Cloning and characterization of purple acid phosphatase phytases from wheat, barley, maize, and rice.

Barley (Hordeum vulgare) and wheat (Triticum aestivum) possess significant phytase activity in the mature grains. Maize (Zea mays) and rice (Oryza sativa) possess little or virtually no preformed phytase activity in the mature grain and depend fully on de novo synthesis during germination. Here, it is demonstrated that wheat, barley, maize, and rice all possess purple acid phosphatase (PAP) genes that, expressed in Pichia pastoris, give fully functional phytases (PAPhys) with very similar enzyme kinetics. Preformed wheat PAPhy was localized to the protein crystalloid of the aleurone vacuole. Phylogenetic analyses indicated that PAPhys possess four conserved domains unique to the PAPhys. In barley and wheat, the PAPhy genes can be grouped as PAPhy_a or PAPhy_b isogenes (barley, HvPAPhy_a, HvPAPhy_b1, and HvPAPhy_b2; wheat, TaPAPhy_a1, TaPAPhy_a2, TaPAPhy_b1, and TaPAPhy_b2). In rice and maize, only the b type (OsPAPhy_b and ZmPAPhy_b, respectively) were identified. HvPAPhy_a and HvPAPhy_b1/b2 share 86% and TaPAPhya1/a2 and TaPAPhyb1/b2 share up to 90% (TaPAPhy_a2 and TaPAPhy_b2) identical amino acid sequences. despite of this, PAPhy_a and PAPhy_b isogenes are differentially expressed during grain development and germination. In wheat, it was demonstrated that a and b isogene expression is driven by different promoters (approximately 31% identity). TaPAPhy_a/b promoter reporter gene expression in transgenic grains and peptide mapping of TaPAPhy purified from wheat bran and germinating grains confirmed that the PAPhy_a isogene set present in wheat/barley but not in rice/maize is the origin of high phytase activity in mature grains.

Genome Editing-accelerated Re-Domestication (GEaReD) - A new major direction in plant breeding.

BACKGROUND: The effects of climate change, soil depletion, a growing world population putting pressure on food safety and security are major challenges for agriculture in the 21st century. The breeding success of the green revolution has decelerated and current programs can only offset the yield affecting factors. PURPOSE AND SCOPE: New approaches are urgently needed and "Genome Editing-accelerated Re-Domestication" (GEaReD) is proposed as a major new direction in plant breeding. By combining the upcoming technologies for phenotyping, omics, and artificial intelligence with the promising new CRISPR-toolkits, this approach is closer than ever. SUMMARY AND CONCLUSION: Wild relatives of current crops are often adapted to harsh environments and have a high genetic diversity. Redomestication of wild barley or teosinte could generate new cultivars adapted to environmental changes. De novo domestication of perennial relatives such as Hordeum bulbosum could counter soil depletion and increase soil carbon. Recent research already proved the principle of redomestication in tomato and rice and therefore laid the foundation for GEaReD.

New Hope for Genome Editing in Cultivated Grasses: CRISPR Variants and Application.

With the advent of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated protein (Cas) mediated genome editing, crop improvement has progressed significantly in recent years. In this genome editing tool, CRISPR-associated Cas nucleases are restricted to their target of DNA by their preferred protospacer adjacent motifs (PAMs). A number of CRISPR-Cas variants have been developed e.g. CRISPR-Cas9, -Cas12a and -Cas12b, with different PAM requirements. In this mini-review, we briefly explain the components of the CRISPR-based genome editing tool for crop improvement. Moreover, we intend to highlight the information on the latest development and breakthrough in CRISPR technology, with a focus on a comparison of major variants (CRISPR-Cas9, -Cas12a, and -Cas12b) to the newly developed CRISPR-SpRY that have nearly PAM-less genome editing ability. Additionally, we briefly explain the application of CRISPR technology in the improvement of cultivated grasses with regard to biotic and abiotic stress tolerance as well as improving the quality and yield.

Barley Nepenthesin-Like Aspartic Protease HvNEP-1 Degrades Fusarium Phytase, Impairs Toxin Production, and Suppresses the Fungal Growth.

Nepenthesins are categorized under the subfamily of the nepenthesin-like plant aspartic proteases (PAPs) that form a distinct group of atypical PAPs. This study describes the effect of nepenthesin 1 (HvNEP-1) protease from barley (Hordeum vulgare L.) on fungal histidine acid phosphatase (HAP) phytase activity. Signal peptide lacking HvNEP-1 was expressed in Pichia pastoris and biochemically characterized. Recombinant HvNEP-1 (rHvNEP-1) strongly inhibited the activity of Aspergillus and Fusarium phytases, which are enzymes that release inorganic phosphorous from phytic acid. Moreover, rHvNEP-1 suppressed in vitro fungal growth and strongly reduced the production of mycotoxin, 15-acetyldeoxynivalenol (15-ADON), from Fusarium graminearum. The quantitative PCR analysis of trichothecene biosynthesis genes (TRI) confirmed that rHvNEP-1 strongly repressed the expression of TRI4, TRI5, TRI6, and TRI12 in F. graminearum. The co-incubation of rHvNEP-1 with recombinant F. graminearum (rFgPHY1) and Fusarium culmorum (FcPHY1) phytases induced substantial degradation of both Fusarium phytases, indicating that HvNEP-1-mediated proteolysis of the fungal phytases contributes to the HvNEP-1-based suppression of Fusarium.

The Value of 68Ga-PSMA PET/CT Following Equivocal 18F-NaF PET/CT in Prostate Cancer Patients.

BACKGROUND: Inconclusive bone scans are a challenge but there is no consensus about follow-up imaging. We evaluated the use of 68gallium-labelled prostate-specific membrane antigen (68Ga-PSMA) PET/CT if 18F-sodium fluoride (18F-NaF) PET/CT was inconclusive. METHODS: This retrospective study included patients with no previously known bone metastases who had one or more equivocal bone lesions on 18F-NaF PET/CT and underwent additional 68Ga-PSMA PET/CT. The bone lesions were deemed as true metastases or not based on follow-up by surveying supplemental imaging modalities and hospital records. A subgroup of patients with "most valid follow-up" was created, which included patients with unmeasurable PSA after prostatectomy or subsequent imaging (additional 18F-NaF PET/CT, 68Ga-PSMA PET/CT, CT, or MRI). RESULTS: Of the 2918 patients referred for 18F-NaF PET/CT from the department of urology in the inclusion period, 51 (1.7%) were inconclusive regarding bone metastases and underwent additional 68Ga-PSMA PET/CT. Thirteen of these patients (25%) were ultimately diagnosed with bone metastases. Patient-based sensitivity, specificity, and accuracy of additional 68Ga-PSMA PET/CT were 100%, 95%, and 96%, respectively. In patients with "most valid follow-up", the same parameters were 100%, 93%, and 94%, respectively. CONCLUSION: 68Ga-PSMA PET/CT is an excellent complementary modality in when 18F-NaF PET/CT is equivocal.

A novel wheat q' allele identified by forward genetic in silico TILLING.

The major wheat domestication allele Q (encoding an APETALA2 like transcription factor) is responsible for the free threshing and square-headed spikes of modern wheat. Wild type q and null q' alleles cause a reversal to the speltoid phenotype. Q pleiotropically affects additional yield and quality traits so genetic variation in Q and its interaction partners remain important for crop improvement. Here we report the discovery of a novel q' allele that contribute to the molecular characterization of Q. This induced mutation cause an Ala→Thr substitution at a highly conserved position in the first of two APETALA2 like domains of the Q protein. The mutation correlates with a speltoid phenotype as expected for a loss of Q function. Thus, it is demonstrated that the first APETALA2 like domain is essential for Q function. The phenotype was discovered in a mutant from an in silico TILLING population and the causative mutation could be identified in the existing sequence data. This report therefore provides an example of a forward genetic application of in silico TILLING.

Horizontal Stacking of PAPhy_a Cisgenes in Barley Is a Potent Strategy for Increasing Mature Grain Phytase Activity.

Mature grain phytase activity (MGPA) in the Triticea tribe cereals has evolved through gene duplications and neo-functionalization of the purple acid phosphatase phytase gene (PAPhy) in a common ancestor. Increased gene copy number of the PAPhy_a gene expressed during seed development has augmented the MGPA in cereals like rye and wheat. PAPhy_a phytase is highly stable and a potent enzyme in feed. However, barley only contains one HvPAPhy_a gene and the MGPA levels needs to be increased to substitute for the addition of microbial phytases to the feed. A substantial increase in MGPA for cisgenic barley was achieved with one extra homozygous HvPAPhy_a insert when the plants were grown in the greenhouse. In the current study, the stability of increased MGPA was confirmed in open field grown cisgenic barley. Furthermore, the gene dose response of phytase cisgenes from three different cisgenic barley plants were horizontally stacked. Cisgenic barley with 0, 1, 2, 3, 4, and 6 extra HvPAPhy_a inserts demonstrated a perfect positive linear correlation with the level of MGPA. The current study provides new insight into the potential of stacking of cisgenes in crops and suggests cisgene stacking as a versatile strategy for crop improvement.

A novel family of plant DNA-binding proteins containing both HMG-box and AT-rich interaction domains.

The A/T-rich interaction domain (ARID) and the HMG-box domain represent DNA-interaction modules that are found in sequence-specific as well as nonsequence-specific DNA-binding proteins. Both domains are found in a variety of DNA-interacting proteins in a wide range of eukaryotic organisms. Proteins that contain both an ARID and an HMG-box domain, here termed ARID-HMG proteins, appear to be specific for plants. This protein family is conserved in higher plants (both mono- and dicot plants) as well as lower plants such as the moss Physcomitrella. Since ARID-HMG proteins have not been studied experimentally, we have examined here two family members from Arabidopsis. The genes encoding ARID-HMG1 and ARID-HMG2 are widely expressed in Arabidopsis but at different levels. Subcellular localization experiments studying ARID-HMG1 and ARID-HMG2 fused to GFP by fluorescence microscopy show that both proteins localize primarily to cell nuclei. Analyses of the DNA-binding properties using electrophoretic mobility shift assays revealed that mediated by the HMG-box domain, ARID-HMG1 binds structure specifically to DNA minicircles. Mediated by the ARID, the protein binds preferentially to A/T-rich DNA, when compared with G/C-rich DNA. Therefore, both DNA-binding domains contribute to the DNA interactions of ARID-HMG1. Accordingly, the protein combines DNA-binding properties characteristic of ARID and HMG-box proteins.

Superior Growth Rates in Broilers Fed Wheat with Low In Vitro Feed-Xylanase Inhibition.

Grain-batch variation in xylanase-inhibitor levels may account for variations in the efficacy of feed xylanase supplementation. This would make inhibition an important quality parameter in the routine analysis of feedstuffs. Two analytical procedures for testing feedstuffs against specific xylanases were researched: the high-throughput viscosity-pressure assay (ViPr) and the extraction-free remazol-brilliant-blue-beechwood-xylan (RBBX) assay. Thirty-two wheat cultivars were analyzed for inhibition of a commercial xylanase, Ronozyme WX. Four cultivars were selected for a feeding experiment in which the growth of 1440 broilers from ages 7-33 days was monitored. The treatments resulted up to 7 % difference (day 14) in broiler weight . The cultivar choice had an effect throughout the experiment ( p < 0.05). The performance ranking of the treatments corresponded better to xylanase inhibition than to crude-protein content or nonstarch-polysaccharide content. Wheat-grain xylanase-inhibitor content is therefore a highly relevant quality parameter when broiler diets are supplemented with feed xylanase.

The innovative development in interferon beta treatments of relapsing-remitting multiple sclerosis.

The introduction of interferon beta therapies more than 20 years ago marked a milestone in the treatment of relapsing-remitting multiple sclerosis (RRMS) with a significant impact on the approach to modern multiple sclerosis (MS) care. Key learnings and perspectives from the early days of disease modifying therapies in MS have improved the knowledge base of MS, need for treatment, and patient care. The continuous development of interferons over the past two decades outlines a journey with increased understanding of the pharmacodynamics and pharmacokinetic mechanisms of interferons, leading to innovative formulations with an improved benefit/risk profile.