Journal of Foot and Ankle Research (JFAR) was launched in July 2008 as the official research publication of the Society of Chiropodists and Podiatrists (UK) and the Australasian Podiatry Council, replacing both the British Journal of Podiatry and the Australasian Journal of Podiatric Medicine. This editorial celebrates the 10 year anniversary of the journal. Journal of Foot and Ankle Research (JFAR) was launched in July 2008 as the official research publication of the Society of Chiropodists and Podiatrists (UK) and the Australasian Podiatry Council, replacing both the British Journal of Podiatry and the Australasian Journal of Podiatric Medicine [JFAR was developed to meet the growing need for an international platform for the publication of research within the podiatry profession [JFAR has been published by BioMed Central (now BMC), one of the pioneers of scholarly open access. This editorial celebrates the journal’s 10-year anniversary by summarising the key achievements of the journal between 2008 and 2018.Medicine . JFAR waofession , and theofession . Since iJFAR, with authors from 38 different countries , the annual College of Podiatry conference , and the International Foot and Ankle Biomechanics Community (i-FAB) conference , and five article collections: the Diabetic Foot (2012), the Rheumatoid Foot (2013), the Paediatric Foot (2015) and the Science and Sociology of Footwear (2018).Since July 2008, 442 papers have been published in see Fig. . JFAR haJFAR papers  were foot, physiology, podiatry, gait, ankle, diabetes, shoes, biomechanics, foot orthoses and footwear. A word cloud representing the 150 most common words used in the titles of all 442 papers published in the journal is shown in Fig. According to the Scopus® database, the ten most common keywords used in the abstracts of JFAR receives between 100 and 150 papers each year, of which approximately 50 are accepted for publication. The acceptance rate is trending downwards and is currently 36%. The average time to a first editorial decision for reviewed manuscripts is 55 days, and the average time from submission to acceptance is 112 days (this includes the time taken to find peer reviewers and the time taken for authors to revise their manuscripts). Over the past 10 years, the time taken to find peer reviewers has increased. This reflects the growing global burden of peer review in the biomedical literature, which has been estimated at 63 million hours per year [per year .JFAR, we extracted the first 100 rejected papers from the editorial database, and searched PubMed and Google Scholar in April 2018 using the title, key words and author names of each paper. Of these papers, 39 could not be located in another journal. The remaining 61 papers were subsequently published in 45 different journals , the most common destination journals being The Foot (seven papers) and Journal of the American Podiatric Medical Association (six papers). The time period between rejection from JFAR and subsequent publication in another journal ranged from 0 to 58 months (median 16). These data provide evidence of a journal hierarchy amongst foot and ankle researchers, with papers eventually published in The Foot, Journal of the American Podiatric Medical Association, Diabetic Foot and Ankle, Foot and Ankle Online Journal, Foot and Ankle Specialist and Foot and Ankle Surgery first being submitted to JFAR. However, it is also likely that JFAR receives manuscripts rejected from other journals, particularly specialist biomechanics, sports medicine, orthopaedics, diabetes and rheumatology journals.To determine the fate of papers rejected from JFAR was formally accepted for IF tracking by Thomson Reuters  in November 2011, and received its first IF (1.333) in 2012 [JFAR has the 2nd highest 2-year IF (1.683) and 5-year IF (2.187), behind Foot and Ankle International. The 2-year and 5-year IFs for all foot and ankle journals are shown in Figs. There are several citation-based metrics to evaluate journal performance. By far the most widely used is the Impact Factor (IF), first developed in 1955 [ in 2012 . Since trst IF 1.33 in 201JFAR’s SJR (0.873) is second only to Foot and Ankle International  ranked in 2nd position behind Foot and Ankle International  has been developed by the technology company SCImago Lab . The SJRnal Fig. . Finallynal Fig. .Fig. 5SCJFAR has performed extremely well for a relatively young journal. However, JFAR’s position on citation metrics, as outlined in our 2012 editorial, remains that “rather than agonising over ubiquitous yet flawed journal performance metrics, we will continue to make editorial decisions based on the relevance and scientific quality of individual manuscripts” [These data clearly show that scripts” .JFAR website, the Scopus® database, and Altmetric Attention Scores, respectively. The most accessed manuscript in the 10-year history of the journal is Bristow’s clinical guideline for the recognition of malignant melanoma [The impact of individual papers can be assessed in several ways: the number of accesses, the number of citations, and the number of mentions on social media. Table melanoma , the mosmelanoma , and themelanoma .Table 1TJFAR has published a total of 31 systematic reviews. These reviews have summarised the best available evidence for a wide range of topic areas, including the effectiveness of treatments such as foot orthoses [Another way to assess the relative importance of papers is by applying the hierarchy of evidence, which places systematic reviews above all other study designs, including randomised trials, non-randomised studies, observational studies, case series studies and case reports. In this context, it is pleasing to note that orthoses , stretchorthoses , dry neeorthoses , laser torthoses , prolothorthoses , extracoorthoses  and softorthoses . SystemaJFAR’s dedicated site received 264,565 page views, with an average of 19,214 views per month. The website was accessed by readers from most countries in the world, with the highest number of accesses from the USA , followed by the UK , Australia , India  and Canada (8218). See Fig. The BMC website attracts over 20 million visits each month. In 2017, JFAR has been an early adopter of innovations in academic publishing. Consistent with BMC’s ethos of transparency, we operate an open peer review process (where authors’ and reviewers’ identities are disclosed), and we publish all peer reviews on our website. The BMC platform also allows for non-traditional content to be uploaded to support manuscripts, including video files [As the first foot and ankle journal to fully embrace open access publishing, eo files  and downeo files .JFAR, we will explore all strategies for improving the reader experience while ensuring that the information provided is as accurate and unbiased as possible.Engaging readers, however, particularly time-poor clinicians, is an ongoing challenge for all scholarly journals. Relatively recent innovations to improve readability, engagement and translation include video abstracts  and infoProfessor Hylton Menz  and Professor Alan Borthwick, OBE  will step down from their roles at the end of July 2018. The new Editors-in-Chief will be Professor Keith Rome  and Professor Catherine Bowen , the new Deputy Editors will be Dr. Andrew Buldt  and Dr. Michelle Spruce  and the Associate Editors will be Mr Daniel Bonanno , Dr Cylie Williams  and Dr Anita Williams .JFAR’s success over the past 10 years: past and present editorial colleagues , past and present BMC journal development managers  and past and present Board of Management members . We would also like to thank our editorial board and peer reviewers for their tireless efforts in assessing the suitability of papers for publication.The authors would like to sincerely thank the following individuals for contributing to


The potential of the polyampholytic and polyelectrolytic starch compounds as excipients for drug controlled release was investigated using various tracers differing in terms of solubility and permeability. Ampholytic trimethylaminecarboxymethylstarch (TMACMS) simultaneously carrying trimethylaminehydroxypropyl (TMA) cationic groups and carboxymethyl (CM) anionic groups was obtained in one-step synthesis in aqueous media. Trimethylaminestarch (TMAS) and carboxymethylstarch (CMS) powders were also synthesized separately and then homogenized at equal proportions in liquid phase for co-processing by spray drying (SD) to obtain polyelectrolytic complexes TMAS-CMS (SD). Similarly, equal amounts of TMAS and CMS powders were dry mixed (DM) to obtain TMAS:CMS (DM). Monolithic tablets were obtained by direct compression of excipient/API mixes with 60% or 80% drug loads. The in vitro dissolution tests showed that ampholytic (TMACMS) and co-processed TMAS-CMS (SD) with selected tracers ), were able to control the release even at very high loading (80%). The presence of opposite charges located at adequate distances may impact the polymeric chain organisation, their self-assembling, and implicitly the control of drug release. In conclusion, irrespective of preparation procedure, ampholytic and polyelectrolytic starch materials exhibited similar behaviours. Electrostatic interactions generated polymeric matrices conferring good mechanical features of tablets even at high drug loading. Oral solid dosages  have always been among the most studied galenic forms in pharmaceutical development. The interest in modifying their release led to sustained investigation efforts aimed to develop new technologies, formulas, or devices to control the drug release. The expectations and, in a large measure, the achievements of drug delivery systems (DDS) were to optimize the treatments by administering precise doses (avoiding under/overdose) , targeti®) of active pharmaceutical ingredient (API) [®) [Starch is one of the most studied biopolymers known for its biocompatibility, biodegradability, and abundant sources as well as for the different possibilities of modification  offered by its hydroxyl groups (–OH) . Starch nt (API)  and, at API) [®) . DespiteAPI) [®) .Starch excipients functionalized by substitution of -OH as starch acetate (SAc), aminoethyl starch (AES) or carboxymethyl starch (CMS) excipients have different features depending on their chemical nature ,16. The Generally, the starch derivatives can be synthesized either in organic or inorganic media. The drying step can be carried out by precipitation (methanol/acetone), lyophilization, or spray drying. A correlation between the DS, the drying method, and the physicochemical properties of the CMS was previously shown . The CMSIn the present study, a new form of ampholytic starch was investigated. This new derivative carries quaternary amine and carboxymethyl groups. It was synthesized by simultaneous starch treatment with glycidyltrimethylammonium chloride and sodium chloroacetate to obtain trimethylaminecarboxymethylstarch (TMACMS). Separately, starch derivatives carrying only cationic groups: trimethylaminestarch (TMAS) or anionic groups: carboxymethylstarch (CMS) were also synthesized. For a better understanding of mechanisms governing the drug release from these new types of starch derivatives, the impact of the physical processing on the release of selected active molecules was also explored. Thus, the anionic and the cationic starch derivatives were mixed by two different methods to obtain polyelectrolytes: 1) co-processing by spray drying (SD) of the aqueous mixtures of TMAS and CMS to obtain polyelectrolyte complexes abbreviated as TMA-CMS (SD) or 2) by dry mixture (DM) of powders of each compound at room temperature, abbreviated as TMA-CMS (DM). All derivatives were structurally characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (DRX), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), as well as by micromeritic studies. All new products were used as excipients for monolithic tablets with model active molecules having different solubilities and ionic charges.High amylose starch (Hylon VII) was supplied by National Starch/ Ingredion . Mesalamine  was obtained from PharmaZell . Naproxen and atenolol were purchased from Sigma-Aldrich . Sodium monochloroacetate (SMCA) was from Sigma-Aldrich . Glycidyltrimethylammonium chloride (GTMAC) and acetaminophen were from Sigma-Aldrich .− (CMS) with negative overall charges or carrying quaternary amine groups –N+(CH3)3 (TMAS) with positive overall charges. The polyelectrolytic complexes were produced by i) co-processing by spray drying (SD), ii) homogenization of powders by direct physical mixing (dry mixed (DM)), iii) the third product was: TMACMS, an ampholytic starch carrying carboxylic groups (CM) and quaternary amine groups (TMA) on the same starch backbone synthesized in an one-step chemical process by adding simultaneously SMCA and GTMAC to the gelatinized starch. To synthesize polyelectrolytic complexes, CMS and TMAS were prepared separately using almost the same steps as in previous described by Sakeer et al. [v/v) and washed by decantation with the same solution until the preparation had a conductivity below 100 μS/cm. The slurry was then washed by filtration with pure acetone for final drying under vacuum. The obtained CMS and TMAS powders were left overnight at room temperature and then sieved to retain particles smaller 300 µm. Ampholytic starch TMACMS was prepared by the chemical process as previously described by Sakeer et al. [v/v) and washed by decantation with the same solution until the preparation had a conductivity lower than 100 μS/cm. The slurry was then washed by filtration with pure acetone for final drying under vacuum. The powder was left overnight at room temperature and only particles smaller than 300 µm were retained after sieving. The polyelectrolyte TMAS-CMS (SD) was obtained separately: 10 g of CMS were completely dissolved in 1 L distilled water (solution 1). Separately, 10 g of TMAS were completely dissolved in 1L distilled water (solution 2). Solutions 1 and 2 were mixed and spray drayed  at 200 °C. The obtained TMAS-CMS (SD) powder was left overnight in an oven at 40 °C to eliminate all humidity. The polyelectrolyte blend TMAS:CMS (DM) was obtained by direct mixing of powders (50:50 w/w) for homogenization.The aim of synthesis was to obtain three excipients based on modified starch: two polyelectrolyte starch derivatives carrying carboxylic groups –COOr et al. , slightlr et al. . Brieflycoo-) of CMS was determined by back titration. An amount of 200 mg of polymer was solubilized in 20 mL of NaOH (0.05 M) and the excess of NaOH (unreacted with carboxylic groups) was titrated by HCl (0.05 M). Color change of the indicator phenolphthalein was determined as the equivalence point. Twenty milliliters of NaOH (0.05 M) were also titrated and used as blank. All the titrations were done in triplicate. The DScoo- was obtained by calculating the amount of carboxylic groups as follows:bV and sV are the volumes (L) of HCl (0.05 M) for titration of blank and samples respectively; HClC is the concentration of HCl (mol/L); 162 (g/mol) molecular weight of one glucose unit; 58 (g/mol) is the increase in the weight of one glucose unit after substitution of hydroxyl groups by carboxymethyl group, and m (g): mass of dry powders. The degree of substitution of hydroxyl group by trimethyl amine group (DS N+(CH3)3) of TMAS and TMACMS were calculated by elemental analysis. Results were given by percentage of molecular mass for each element.The degree of substitution at level of –OH by carboxymethyl groups .FTIR spectra of Hylon VII, CMS, TMAS, and polyelectrolytic starch powders were recorded by a Thermo Scientific, Nicolet 6700/Smart iTR  using a diamond crystal with 64 scans/min at 4 cmThe polymorphism of powders was evaluated by X-ray diffractometry using a Bruker, D8 Advance  device. A copper cathode (Cu Kα) was used in reflectance mode with a scanning rate of 0.05°/min. All patterns were analyzed through a 2θ range of 5°–50°. EVA software was used for X-ray diffraction spectra treatments.w/v) in nonopure water. The analysis of particle surface charges was carried out at 25 °C using 1 mL of suspension. Measurements were done in triplicates.The zeta potential of polymers was measured by ZetaPlus/Bl-PALS . Polymers were dissolved (0.01% w/v) at room temperature. All measurements were done in triplicates.A Cole-Parmer PC200S pH/mV/Cond  was used to measure the pH of sample suspension (polymer: nanopure water 2.5% The morphology of powders of native starch (Hylon VII) and of starch derivatives was investigated using a Hitachi (S-4300SE/N) scanning electron microscopy with variable pressure . Powder samples were put on a support covered by a double-sided carbon tape and sputter-coated with gold. The magnification was 100× and 1000× for all samples using.The weight loss depending on the variation of temperature was measured by a Q500 TGA Thermogravimeter  between 30 and 700 °C at 10 °C/min in a nitrogen atmosphere at 100 mL/min, using a small amount of powder filed on a platinum crucible. The analysis was carried out until the complete disappearance of the samples. “TRIOS” software was used for treatment of results.θ) was determined using the fixed funnel method [h stands for height; and r for ray.Micrometric tests are used to study physicochemical properties of the obtained powders; they have been carried out according to USP recommendations using a Tap Density Tester . The powder’s characteristics were studied using <1174> USP method  and the l method  and calcr” is the ray of the base and “h” is the height of the cone (2 cm). Compressibility index (CI) and Hausner’s factor (HF) values were obtained according to the ˂616˃ USP [tab) and bulk density (ρbulk). Briefly, a known mass of powder is placed in a graduated cylinder, the corresponding volume (mL) is noted. The ratio mass (g) volume (mL) is called bulk density which represents the density of a powder including the spaces between the particles. Tapped density was obtained by tapping the same cylinder using Tap Density Tester  until there was a new volume of powder (elimination of space between the particles). Tapped density was represented by ratio mass (g):volume (mL). CI and HF were calculated as follows:The powder was poured into a funnel fixed 2 cm from a flat surface. The passage of the powder formed a cone. “616˃ USP  by measu2) using flat-faced punches with 12.9 mm diameter  to obtain monolithic round tablets. For in vitro dissolution assays, the same excipients were used to prepare 12.9 mm diameter monolithic tablets with two different loadings. For acetaminophen or naproxen, 500 mg of API powders were homogenized with 333 mg or 125 mg of powdered polymers to obtain respectively 60% and 80% API loaded tablets. For mesalamine, 400 mg of API were homogenously mixed with 267 mg or 100 mg of polymers to obtain respectively 60% and 80% API loaded tablets. For atenolol, 9 mm flat-faced punch was used because of the small amount of powder: 200 mg of API powders were homogenized with 133 mg or 50 mg of powdered polymers to obtain respectively 60% and 80% atenolol loaded tablets. For all APIs, equal amounts of TMAS and CMS powders were dry mixed (DM) to obtain TMAS:CMS (DM).To determine swelling, fluid uptake, and erosion, drug-free tablets (placebos) were prepared. CMS, TMAS, and polyelectrolytic or ampholytic starch powders were directly compressed (2.5 T/cmW1) and their diameter and thickness were measured. Then they were immersed in 40 mL of SGF (pH 1.2) and submitted to rotation at 50 rpm  for 2 h. The tablets were then transferred in 40 mL SIF (pH 6.8) and submitted to rotation at 50 rpm. After every 2 h, tablets were withdrawn and weighed at time t (Wt), diameters and thickness were also measured. Finally, tablets were placed in an oven at 40 °C for 48 h to obtain completely dry tablets (Wf).W1 is the weight of the dry tablets; Wt the weight of the tablets at time t; and Wf the final weight of the tablets.Drug-free tablets have been used to investigate the behavior of starch compounds in simulated biological fluids: simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). First, dry tablets were weighed  were immersed in 500 mL SGF at 100 rpm for 2 h and then transferred in 900 mL SIF at 50 rpm. At a predetermined sampling interval, volumes of 3 mL were withdrawn and filtered before a spectrophotometric reading in SGF at λ300nm and in SIF at λ330nm. Naproxen and atenolol tablets (60% and 80% loading) were immersed in 900 mL SGF at 50 rpm for 2 h and then transferred in 900 mL SIF at 50 rpm. At a predetermined sampling interval, volumes of 3 mL were withdrawn and filtered before spectrophotometric reading in SGF at λ224nm for naproxen and λ225nm for atenolol, and in SIF at λ232 nm for naproxen and λ225nm for atenolol. For each analysis, withdrawn volumes were immediately replaced. After each sampling, an equivalent volume (3mL) of dissolution medium was added to the dissolution cell. Standard curves of each drug were used to determine the concentrations of released drugs.In vitro drug release tests have been done following USP requirements for all active agents using a Distek dissolution system 2100A  as USP paddle apparatus II. Acetaminophen tablets (60% and 80% loading) were immersed in 900 mL SGF at 50 rpm for 2 h and then transferred in 900 mL SIF at 50 rpm. At a predetermined sampling interval (1 h), volumes of 3 mL were withdrawn and filtered before spectrophotometric reading at λcoo-) or with cationic groups (DSN+(CH3)3) per glucose unit, was determined by back titration and elemental analysis. The DScoo- was 0.113 for CMS and 0.097 for TMACMS. The DSN+(CH3)3 was 0.195 for TMAS and 0.160 for TMACMS. Solutions of 2.5% in distilled water were prepared for the measurement of pH, the results obtained were: 6.70 for CMS, 7.01 for TMAS, 7.24 for TMACMS, 6.76 for TMAS-CMS (SD), and 7.11 for TMAS:CMS (DM). The zeta potential (ζ) for CMS was ζ = −36.44 mV and for TMAS was ζ = +30.20 mV. The bifunctional starch TMACMS had ζ = +17.26 mV. The zeta potential of TMAS-CMS (SD) and of TMAS:CMS (DM) was -26.28 mV and −32.42 mV respectively.The degree of substitution (DS), which represents the average number of hydroxyl groups substituted with anionic functional groups  at three magnifications and some significant differences were observed . The natθ), which are directly related to flowability of powders. These parameters are dependent on the size, shape, and rugosity of the grain surface [Considering that the new derivatives are proposed as excipients for monolithic tablets, it was useful to evaluate micromeritic properties : Hausner surface . The ang2. The tablets were immersed in 40 mL of SGF for 2 h and then transferred to 40 mL of SIF for 2 h  and for 4 h . The results are shown in Placebo tablets were prepared by direct compression of TMAS, CMS, TMACMS, TMAS-CMS (SD), and TMAS:CMS (DM) powders at 2.5 T/cmAfter transfer to SIF, the swelling continued, unaffected by pH change, and the tablet had burst after a massive fluid uptake (+482.5% after 4 h and +631.6% after 6 h). The TMACMS had a fluid uptake of 275.4% after 2 h in SGF with an increase of diameter of +23.1% and of thickness +34.6%, swelling and minor erosion (−8.3%). The ampholytic starch TMACMS showed a good stability of weight and shape 6 h after transfer to SIF, with a moderate increase of diameter (+41.3%), thickness (+39.6%), and with a limited erosion (−20.1%) reflecting an independent pH behavior . TMAS-CMAbsorption of fluids was proportional to changes in diameter for TMAS-CMS (SD) tablets with +198.2% practically stable for 6 h and an erosion of −21.3% after 6 h. TMAS:CMS (DM) showed a gain of weight 307%, of diameter (+24.9%) and of thickness (+46.4%) after 2 h in SGF. After 6 h in SIF, stability of shapes was observed  with a fIn order to study the release profiles afforded by the new polyelectrolyte excipients, four APIs (tracers) were selected (one for each BCS class) according to their physicochemical properties. Acetaminophen (class I BCS) has a low sensitivity to the ionic strengths of the medium and pH variations (same solubility in SGF and SIF: 20.3 mg / mL) ,35. MesaThe dissolution profiles of tablets with 60% acetaminophen loading showed that TMACMS, TMAS-CMS (SD), and TMAS:CMS (DM) prolong API release up to 24h with 91%, 82%, and 80% release respectively . HoweverIn order to explore the limits of the novel polymeric excipients and to understand the interactions between polymer–polymer and possibly between API and polymeric excipients, dissolution tests were carried out under the same conditions using highly loaded tablets (80% API and 20% excipient). The release profiles are shown in coo-) and (DSN+(CH3)3), pH, and Zeta potential (ζ) were determined. The pH values were close to neutral for all of derivatives. Zeta potential values were in line with the theoretical expectations for CMS due to the presence of a negatively charged CM groups, for TMAS due to the presence of a positively charged TMA groups and for the bifunctional starch TMACMS probably due to the presence of the two types of groups CM and TMA. On the other hand, unexpected negative ζ values observed with TMAS-CMS (SD) and of TMAS:CMS (DM) respectively, could be due to a reorganization of the chains with the orientation of the –COO− polar groups towards the surface contact with the liquid medium [The degree of substitution (DSd medium .−1 attributed to stretching vibration of carboxylic –COO− groups [−1 and the shoulder at 1476 cm−1 could be ascribed to the vibration of methyl groups carried by nitrogen –N+(CH3)3 [−1 and 2980 cm−1 correspond to –OH and –CH stretching vibrations, whereas bands at 1089 and 1000 cm−1 were attributed to –CH2–O–CH2 stretching vibration [−1 and at 1415 cm−1 may confirm a successful synthesis of ampholytic starch. The DS variations would explain the observed difference in bands intensities [The FTIR of CMS  is chara− groups ,38. For N+(CH3)3 ,40. ThisN+(CH3)3 . For natibration . For TMAensities ,43.The X-ray diffraction showed that the native starch has a more organized semi-crystalline structure than its derivatives. The presence of double helix (B-type), shown by specific peaks at 17.09°, 22.13°, 23.52°, and 24.08°, corresponds to the crystalline fraction of native starch . The losThe first loss of mass observed on all samples  was due The morphology of native starch is probably related to the structural stability offered by hydrogen bridges and crystal regions (B-type) . The simFor the angle of repose, a value of less than 30° indicates a good flow while an angle greater than 56° indicates a bad flow. The HF values lower than 1.2 indicate a good flow of powders but a poor cohesion and compressibility, whereas a HF greater than 1.2 indicates a poor flow and a good cohesion and compressibility ,49. The The three derivatives with ampholytic features TMAS-CMS (DM), TMA-CMS (SD), and TMACMS exhibited different swelling behavior: TMAS:CMS (DM) shows a faster fluid uptake and a greater swelling compared to TMA-CMS (SD) and TMACMS. Furthermore, the thickness of the TMAS:CMS (DM) tablet decreases after transfer from SGF to SIF due to faster hydration. The TMA-CMS (SD) placebo tablets show a stable profile (swelling and erosion) especially in SIF, while TMACMS shows a slight change in size due fluid uptake.−, –N+(CH3)3) in an aqueous medium than in the dry phase [The dissolution tests performed with placebo tablets showed that TMACMS, TMAS-CMS (SD), and TMAS:CMS (DM) provided longer tablet integrity, for at least 6 h (2 h SGF + 4 h SIF) compared to CMS and TMAS excipients. In SGF, rapid swelling was found due to protonation of carboxyl groups. Once in SIF, TMACMS and TMAS-CMS (SD) display a better stability than TMAS, CMS, and TMAS:CMS (DM); this could be explained by a stronger electrostatic interaction between cationic and anionic starch derivatives  starch polymeric excipients showed the best release profiles, even at very high loading. These excipients would be of interest for sustained release systems, especially for high daily dosages of drugs. Simultaneous presence of opposite charges would provide better polymer stability and slow down tablet hydration. Electrostatic interactions strongly impact the microcrystalline organization, in addition to the hydrogen bridges, enhancing their stability. In some particular cases, polymer–drug interactions would influence release patterns. Further investigations concerning the degree of substitution, the ratio of cationic/anionic charges, and also intra- and inter-molecular interactions, would provide greater clarity in stabilization mechanism of starch compounds.


A reformatted journal demands a new Editor-in-Chief. Over the last year, thepaper-printed Journal of the Belgian Society of Radiology has gone through aradical and successful transformation into a fully electronic open medium on anadvanced IT platform. The time has thus become right for me to step down asEditor-in-Chief A reformatted journal demands a new Editor-in-Chief. Over the last year, thepaper-printed Journal of the Belgian Society of Radiology has gone through a radical andsuccessful transformation into a fully electronic open medium on an advanced ITplatform. The time has thus become right for me to step down as Editor-in-ChiefLast November, during the annual Symposium of the Belgian Society of Radiology, President Geert Villeirs appointed Dr Alain Nchimi as the new Editor-in-Chief. Dr Nchimi has earned his Medical Degree and completed a Master Degree in Medical Imaging at the University of Liège. In 2015 he obtained a PhD from the same University. He acquired a diversified professional experience successively in paediatric radiology and nuclear medicine at Great Ormond Street Hospital in London and at the Centre Hospitalier Chrétien in Liège in body imaging and paediatric radiology in the Medical Imaging Department as a consultant, and finally as the Head of the Cardio-Vascular and Thoracic Imaging Department in the Medical Imaging Department of the University Hospital of Liège. He became an Associated Professor of Medical Imaging in 2015. Currently he is a Body Imaging and Paediatric Radiologist in the Medical Imaging Department of the Hospital Center in Luxembourg. He is a member of the Belgian Society of Radiology chairing the Section of Cardio-Vascular Imaging, the European Society of Radiology, the European Societies of Thoracic Imaging and of Cardiac Imaging, as well as the European Association of Cardio-Vascular Imaging and the European Society of Cardiology. Dr Nchimi has published numerous book chapters and peer-reviewed research papers in national and prominent international journals such as Radiology, AJR, British Journal of Radiology, and European Radiology. He has served as a reviewer in at least nine radiological and clinical journals among which are JBR-BTR, European Radiology, AJR, Circulation, and the The International Journal of Cardio-Vascular Imaging. Dr Alain Nchimi’s exemplary experience in clinical research and academic radiology qualifies him highly for the position he has been newly appointed for.The Journal of the Belgian Society of Radiology (JBSR) is the follower of a more than 100-year-old national radiological journal founded in 1905. Over the years the journal has changed its title, its format, the language used, and authorship [1]. The original title in French, Journal Belge de Radiologie (J.belg.radiol), continued until 1976. Subsequently, it became bilingual ) and later the acronym JBR-BTR was used until June 2015.In 1995 the content of the journal was restricted to diagnostic and interventional radiology, related sciences and continuing education. The journal then started publishing in English and, over the last couple of decades; the authorship grew to become more international. During its long existence the journal was constantly supported as the organ of the Belgian Society of Radiology by the board and its subscribers, mostly the members of the society. The number of non-members subscribing, often through international libraries, remained stable and contributed to the diffusion of the journal among others at the Harvard Medical School and the Chinese University of Shanghai. During the last thirty years indirect sponsoring by radiological firms increased in importance, particularly under the action of the last two editorial managers, Daniel Meire and Patrick Seynaeve.The swift implementation of the decision of the Board to move to the electronic-only edition of the journal was more complicated than expected, the devil lying in many details. However, thanks to the outstanding efficiency of the editorial team, in particular the Associate Editor Piet Vanhoenacker and the Ubiquity Press Editorial Manager Sam Hall, as well as with the support of the president of the Board and of the Scientific Committee, publication of the JBSR on the dedicated website was only slightly delayed. Issue two is more delayed due to the backlog of manuscripts to be edited after the closure of the Brussels editorial office last September – a temporary collateral damage.Looking ahead, the future of the JBSR is in great hands for the best development with the advanced Ubiquity Press platform.Personally I am very proud of what has been accomplished together with the editorial team during the last 40 years. In particular Mrs Jocelyne Burion, who was in charge of the processing and editing of the manuscripts, has been of immense help.I am confident about the bright future of the JBSR and look forward to its future development.Jacques PringotEmeritus Editor-in-Chief


We also assigned so far unreported non-reducing end groups and assessed starch chain length, crystallinity and amylose content. Starch was then characterized in situ, i.e., by 13C solid-state NMR of intact microalgal cells. Our in-cell methodology also enabled the identification of the effect of nitrogen starvation on starch metabolism. This work shows how solid-state NMR can enable the identification of starch structure, chemical modifications and biosynthesis in situ in intact microorganisms, eliminating time consuming and potentially altering purification steps.Starch is the most abundant energy storage molecule in plants and is an essential part of the human diet. This glucose polymer is composed of amorphous and crystalline domains in different forms (A and B types) with specific physicochemical properties that determine its bioavailability for an organism, as well as its value in the food industry. Using two-dimensional (2D) high resolution solid-state nuclear magnetic resonance (SS-NMR) on  Starch is, with cellulose, the most abundant carbohydrate that is found in nature. Composed of a polymer of glucose in semicrystalline granules, it is the major form of energy storage for plants . It is ad-glucan linkages) and linear amylose  [1 space group [In the Plantae, starch is stored in grains, structured on different scales, as illustrated in linkage) , the mailinkage) ,9, whilece group , forming13C chemical shifts. In particular, the multiplicity of the C1 carbon is used to distinguish the two starch crystalline forms [2 to C5 resonances, however, are poorly resolved on 1D spectra, and 2D SS-NMR has not yet been used to unambiguously characterize A-type starch, amorphous- and amylopectin-rich starches. To the best of our knowledge, only pure synthetic amylose has been described by 2D 13C NMR and proved to be in the B-type form [One of the limitations of the starch industry is the difficulty to control the final product quality. Today, native starch and its derivatives are most frequently characterized by powder X-ray diffraction ,11, oftene forms ,15,16. Type form .Chlamydomonas reinhardtii—A photosynthetic model organism with well-known metabolism [13C labelling. This microorganism produces starch of the A-type after purification [C. reinhardtii cells, and to identify the type of starch in the storage grains, as well as the level of crystallinity. This work demonstrates how 2D 13C SS-NMR methodology can prove invaluable for the functional in vivo study of starch in its native environment: the cytosol.In this work, we used the microalga tabolism ,19,20, ntabolism ,22—for sfication ,23. Usin13C assignment of pure A, B and amorphous starches. The A and B forms can respectively be obtained with sufficient high crystallinity using amylopectin-rich and native retrograded starches.To characterize starch in situ, we first needed to establish a complete unambiguous st 2-1 amylopectin-rich C. reinhardtii strain. This strain produces starch with the highest crystallinity—about 71% according to our SS-NMR results  as described by Paris et al. [The A form was prepared using starch from the ults see . The shoults see  are typiy SS-NMR . Finallys et al. . The amos et al. ,26.1, C4 and C6 carbons are readily resolved on the 1D spectra of types A, B and amorphous starch, carbons 2 to 5 cannot be distinguished. Gidley and Bociek [1′ peak  have been explained as resulting from the different space groups adopted by A and B forms [As shown in d Bociek  demonstr[1′ peak C. The C1 B forms . These s13C labelled material, including whole cells. As we showed in a previous piece of work, microalgae can easily be fully 13C labelled using NaH13CO3 [A major improvement in resolution can be obtained using 2D methods on NaH13CO3 . A higheNaH13CO3 ,30. ThisNaH13CO3 ,32. MoreNaH13CO3 . Here, wNaH13CO3 ,34.C. reinhardtii native starch (B-form) and dry amylose (amorphous) are shown in The 2D INADEQUATE spectra of amylopectin (A-form), retrograded 1 and C4 carbons [1 value ranges from 99.3 to 101.8 ppm in A-type starch, from 100.1 to 100.9 ppm in B-type and is equal to 103.0 ppm in amorphous starch. The difference in splitting of the C1 peak between A- and B-types is confirmed and extends to the C2 carbons for B-type starch, although this difference is lost in the following carbons, except for the C5 carbon of the B-form. Although chemical shift differences are small, a clear splitting is seen for C5 in the C5–C4 and C6–C5 correlation in the B-form spectrum, which is not present in the A-form ; however, a large 3.9 ppm difference is observed when starch becomes amorphous. Similarly, the difference between C3 chemical shifts in both crystalline forms is minor , however these can clearly be distinguished from the amorphous chemical shift (75.3 ppm). Overall, differences in chemical shifts between A and B forms are small, indicating that the torsion angles and magnetic environment are very similar. The structures are thus locally equivalent and the notable differences that we detected for the C1 resonances, and which we showed to partially extend to other carbons, result from differences on a longer scale, such as the symmetry of the crystal lattice.As seen on the 1D spectrum and as previously reported, the greatest chemical shift differences between starch forms are observed for the C carbons . The C1 e A-form . The cha5 carbon). These resonances cannot arise from soluble molecules, such as short carbohydrate oligomers, because they would have been eliminated in the various washing steps of our samples. On the other hand, the chemical shifts of this system of correlated carbons are in excellent agreement with those reported for the end-groups of synthetic alpha dextrins [Most importantly, all 2D spectra reveal a clearly distinct spin system  that has never been reported in natural starches to the best of our knowledge, most likely because they are almost undetectable on 1D spectra  cells that are absent in whole starchless mutants (see the dashed lines and circled peaks in 1 to C6) and one correlation at 96.7 ppm/75.0 ppm. We suspect them to be co-products of starch synthesis in cells that in situ SS-NMR of various C. reinhardtii strains has allowed to detect. An assignment of those peaks is preliminary at best, however the chemical shifts of the six correlated carbons could correspond to those observed in high-energy twisted starch helices associated with starch synthesis in the cell [Our approach can be applied to other microorganisms, however also to mutants of e strain . The maithe cell ,51.C. reinhardtii strains under nitrogen-rich and nitrogen-deprived diets. The effects are such that simple 1D NMR and spectral subtraction are enough to isolate starch signals. For example, after six days of cell culture, the difference spectrum between the wt strain and the starchless mutant (sta 6-1) leads to an in situ starch spectrum with a fairly good resolution (sta 3-3) and amylose-rich (strain st 2-1) starch producing mutants, starch overproduction is so intense that a subtraction of its spectrum to that of microalgal cells grown in normal medium resulted in an in situ spectrum of starch (data not shown).In cells, SS-NMR can also be used to monitor cellular growth under different conditions. Indeed, we have compared various solution . This tysolution . SimilarC. reinhardtii’s main nutrient.Although nitrogen depletion initially leads to detectable starch overproduction, starch signals were comparable to those of normal cells after one month. More than 80% of microalgal cells survived without any addition of carbon or nitrogen sources because starch reserves had become 13C SS-NMR under magic-angle spinning. During the course of the experiments, microalgae might die from a combination of spinning, heating and starving, however the structures of most of their constituents remain intact. In cells, 13C SS-NMR is thus a versatile approach that enables the identification of starch in microalgae, the comparison of various strains or growth conditions and the study of algal metabolism by monitoring the amount of starch and its progressive degradation throughout the cell life. Starch accumulation, which is a well-known metabolic response to stress, suggests that whole cell SS-NMR experiments could be a useful tool to monitor stress in microalgae.Living microalgae were introduced in the NMR spectrometer and were monitored by 13C-labelled (99%) sodium bicarbonate was obtained from Cambridge Isotope Laboratories  or Martek Isotopes LLC . Natural abundance maize starch, all chemicals used for the growth medium, starch extraction and cell viability assays, such as Percol® and Fluorescein DiAcetate (FDA) were purchased from Sigma-Aldrich .Strains. Wild type strain of Chlamydomonas reinhardtii 222+ was obtained from the collection of the Institut de Biologie Physico-Chimique . Other strains were obtained from the Chlamydomonas Resource Center at the University of Minnesota (http://chlamycollection.org/). Strains sta 3-3 , st 2-1e mutant ) and stae mutant ,55) are Algal growth. Tris minimal medium buffered with HCl to pH 7.3 was made as described by Surzycki [2 and O2 through gas nitrogen bubbling before sealing the Erlenmeyer. Thereafter, the cells were grown under continuous white light illumination (100 µmol photons·m−2·s−1) at 23 °C ± 1 °C with gentle agitation (100 rpm). Five days were needed to reach the exponential phase (5.106 cell/mL). Cells were harvested after 1500× g centrifugation for 10 min. For 13C labelling, labelled sodium bicarbonate (NaH13CO3) was used as the carbon source at 1 g/L in the Tris minimal medium.Surzycki . BrieflyWhole cell experiments. For whole cell experiments, microalgal cells were centrifuged, then rinsed twice with a buffer containing 86 mM NaCl and ~50 mg were packed in a 3.2 mm Varian NMR rotor.Starch overproduction. As larger volumes are needed for starch purification, a 300 mL preculture of wild type C. reinhardtii was grown to 4 × 106 cells/mL and then 50 mL of this solution was added to 2.5 L of medium contained in a 6 L Erlenmeyer. Again, cells were harvested in the exponential phase (5–6 × 106 cells/mL) after 6 days. Starch overproduction in mutant strains was achieved via nitrogen starvation using the medium described by Ball et al. [l et al. , consistg and 4 °C. Cells were rinsed twice with HEPES buffer  and were then centrifuged again.We adapted the protocols of starch extraction from Buléon and co-workers . Briefly8 cells/mL in the same buffer and was disrupted using a homogenizer . Cells were passed through this cell homogenizer 4 times at 10,000 psi and were centrifuged at 2000× g for 20 min, thus pelleting big cell debris and starch granules. Starch was washed several times with Milli-q water and was further purified using Percol® (one volume starch for 4 volumes of Percol). The final pellet was considered as pure native starch and was used without further purification for XRD and NMR. For storage that was longer than 3 days, starch was lyophilized. NMR and XRD tests proved that rehydrated starch reaches the same structure than the native one. For NMR experiments, starch was hydrated and ~50 mg was packed in a 3.2 mm Varian NMR rotor.The cells pellet was diluted to 10w/w suspension) at 100 °C in a sealed glass tube. The resulting gel was then slowly cooled and stored at 4 °C. After one month, B-type XRD patterns were observed . A total of 1000 intact cells were acquired for each sample. This test measures the natural chlorophyll fluorescence and FDA-derived fluorescence generation based on esterase activity level . Briefly13C and 599.95 MHz for proton (1H) using a Varian 3.2 mm magic-angle spinning (MAS) triple resonance probe . The spinning frequency was set to 15 kHz and the probe was kept at room temperature corresponding to a sample temperature of approximately +35 °C for all experiments. 1D (single-pulse (SP) and cross-polarization (CP)) as well as 2D experiments ) were recorded with nutation frequencies of 60 kHz and 75 kHz for carbon and proton channels, respectively (corresponding to 4.2 and 3.35 µs 90° pulses) [1H to 13C, with a 3 s recycle delay (1 s for NOE), an acquisition time of 25 ms, a total of 768 t1 increments of 32 scans and quadrature acquisition using the states-Time Proportional Phase Incrementation (TPPI) method . The delay τ during which the J couplings evolve was set to 2 ms. For NOE-INADEQUATE spectra, an NOE delay of 1 s was used. 13C chemical shifts were externally calibrated with respect to adamantane fixing the CH2 resonance at 38.48 ppm [All spectra were recorded on a Bruker Avance III-HD  operating at a frequency of 150.87 MHz for  pulses) ,30,33,608.48 ppm . SpectraBruker D8 Advance  diffractometer operating at 40 mA and 40 V. The Cu Kα radiation (λ = 1.5406 Å) was selected using a motorized slit of 0.681 nm. Data were recorded in triplicate, with incident angles (2θ) ranging from 2° to 60°, and signals were averaged prior to normalization. Diffractograms were normalized to the same total area under the scattering curve over the Bragg angle range 5–45° (2θ).X-ray diffraction was performed on dry or wet samples (~130 mg). Patterns were recorded in transmission mode on a Crystallinity was assessed by SS-NMR using the method proposed by Lopez and co-workers  on 1D CP13C INADEQUATE NMR experiments enabled, for the first time, the assignment of the C2, C3 and C5 sites in different starch samples. This work confirmed differences that were observed previously between various starch types, and also added C3 and C5 chemical shifts and multiplicity to discriminate between them. Furthermore, full new spin systems were described for amorphous starch and non-reducing end groups of starch. 13C SS-NMR spectra also allowed the assessment of starch crystallinity, disorder and dynamics, and could also be used to evaluate the chain length and amylose/amylopectin content.In this work, we presented an unambiguous full assignment of native and retrograded starches in the A and B forms, amylose- and amylopectin-rich starches. The high resolution that was obtained in 2D in-cell SS-NMR measurements with sufficient resolution to distinguish amorphous, A- and B-type starches, without any time-consuming and potentially altering purification steps. Moreover, we showed that starch crystallinity can be assessed in the cell. The application of this methodology to various C. reinhardtii mutants under different growth conditions and the detection of by-products of starch biosynthesis and its metabolism show how this approach could be applicable to the in situ study of other microorganisms. This work also represents a solid base to study physicochemical functionalisation of starch matrices and starch degradation in bioenergy, food industry or drug delivery contexts, for example.This study is a step forward in the differentiation between saccharides within a microalgal cell. It is the first one reporting


In seeds, the endosperm is a crucial organ that plays vital roles in supporting embryo development and determining seed weight and quality. Starch is the predominant storage carbohydrate of the endosperm and accounts for ∼70% of the mature maize kernel weight. Nonetheless, because starch biosynthesis is a complex process that is orchestrated by multiple enzymes, the gene regulatory networks of starch biosynthesis, particularly amylose and amylopectin biosynthesis, have not been fully elucidated. Here, through high-throughput RNA sequencing, we developed a temporal transcriptome atlas of the endosperms of high-amylose maize and common maize at 5-, 10-, 15- and 20-day after pollination and found that 21,986 genes are involved in the programming of the high-amylose and common maize endosperm. A coexpression analysis identified multiple sequentially expressed gene sets that are closely correlated with cellular and metabolic programmes and provided valuable insight into the dynamic reprogramming of the transcriptome in common and high-amylose maize. In addition, a number of genes and transcription factors were found to be strongly linked to starch synthesis, which might help elucidate the key mechanisms and regulatory networks underlying amylose and amylopectin biosynthesis. This study will aid the understanding of the spatiotemporal patterns and genetic regulation of endosperm development in different types of maize and provide valuable genetic information for the breeding of starch varieties with different contents. Zea mays) is one of the most important food and feed crop sources worldwide. The mature maize seed consists of the endosperm, embryo, and seed coat, and the endosperm occupies ∼85% of the seed volume and is a critical tissue influencing the maize grain weight  gene not only affects the fate and differentiation of aleurone cells but also alters the accumulation and synthesis of reserve metabolites by regulating widespread gene expression  yields maize kernels with a higher amount of amylose than the levels found in nonmutant kernels , granule-bound starch synthase (GBSS), soluble starch synthase (SS), starch branching enzyme (SBE), and starch debranching enzyme (DBE). Starch consists of two types of polysaccharides, namely, amylose and amylopectin, and the ratio of amylose to amylopectin determines the suitability of starch for particular end-uses, such as gelatinisation/gelation characteristics, solubility, the formation of resistant starch, cooking, textural characteristics, and digestibility or nutritional values . Thus, t kernels . Additio kernels . These tHowever, the gene network that links endosperm development with starch synthesis remains unclear. The development of high-throughput technology has resulted in a massive increase in the amount of RNA-Seq data available, and these data are highly reproducible, with few systematic discrepancies among technical replicates . MoreoveZea mays. L) hybrid Shandan 609 (SD609) and the high-amylose maize hybrid high-amylose 68 (HS68) were grown under field conditions at a density of approximately 67,500 plants ha−1 in the summer of 2013 in Yangling, Shaanxi Province, China. The ears were bagged prior to silk emergence and then subjected to manual self-pollination. Three biological replicates of the ears were harvested at 5, 10, 15 and 20 DAP. To ensure the integrity and specificity of the endosperm tissues and the absence of contamination by any other tissues, all slightly damaged endosperm tissues were discarded, and only complete tissues were frozen immediately in liquid nitrogen and stored at −80 °C prior to RNA extraction.The common maize  following the manufacturer’s instructions. RNA sequencing libraries were constructed according to the standard Illumina protocol and were sequenced using the Illumina HiSeq™ 2000 platform to generate 2 ×100-nucleotide paired-end reads .http://www.ncbi.nlm.nih.gov/sra) under the accession numbers SRP065059 and SRP149609.The sequence data obtained in this study have been deposited in the National Center for Biotechnology Information Sequence Read Archive (http://www.maizesequence.org/) using the Tophat2  programme with Bowtie2 read alignment software (http://cole-trapnell-lab.github.io/cufflinks). The expression level was calculated in fragments per kilobase of transcript per million fragments mapped (FPKM) as described previously  (http://www.cytoscape.org/download.php), and the layout was set based on an edge-weighted spring-embedded layout  . We sele/WGCNA/) , which md layout .https://www.genome.jp/kegg/) and agriGO  . The 2,000 bps upstream of the start codons were analysed using the online software PLANTCARE  . A gene patterns . PromoteLANTCARE . If the LANTCARE .GRMZM2G082484) as the internal control. The amplification conditions were 95 °C for 15 min and 40 cycles of 95 °C for 10 s, 60 °C for 20 s and 72 °C for 30 s, and these steps were followed by a melting curve programme (95 °C for 10 s followed by an increase from 65 °C to 95 °C in 5-s increments of 0.5 °C) to confirm the specificity of the PCR amplification. The relative expression levels were calculated as previously described  using SYBR Green I (Bio-Rad) and a CFX96 real-time PCR detection system . The gene-specific primers used in this assay were designed using Primer Premier 5.0 software  and are listed in escribed .To eliminate interference from other ingredient, fat was removed using diethyl ether prior to the isolation of starch, and 200 g of corn flour was then steeped in 1,000 mL of distilled water. The mixture was evenly stirred, and the homogenate was passed three times through a high-precision stainless-steel sieve (150 mu/0.106 mm) to improve the purity of the isolated starch. The slurries were then poured into 50-mL centrifuge tubes and centrifuged at 2,000 rpm for 20 min. This procedure was repeated three times. The supernatant in the centrifuge tube was then discarded, and the sediment was suspended in 40 mL of 0.5% (w/v) sodium hydroxide solution for at least 4 h. The supernatant was discarded, and 40 mL of new 0.5% (w/v) sodium hydroxide solution was added. After the mixture was evenly stirred, the centrifuge tube was centrifuged at 4,000 rpm for 10 min. These steps were repeated three times. Subsequently, 30 mL of absolute ethanol was added to the centrifuge tube, and the tube was centrifuged at 4,000 rpm for 10 min. The final sediment was then oven-dried (40 °C) or air-dried and ground using a mortar and pestle. The amylose content of the B73 starch was determined from the size-exclusion chromatography weight distributions of the debranched starch and was calculated as the ratio of the area under the curve of the amylose branches (defined to have a degree of polymerization P 100) to the area under the curve of the entire distribution (including both the amylopectin and amylopectin branches) . The amyTo obtain global transcriptome maps of the early endosperms of maize with different amylose contents, we performed an RNA-Seq analysis of the common maize SD609 (average amylose content of 27.70%) and the high-amylose maize HS68 (average amylose content of 50.76%) . SpecifiTo gain insight into the temporal and spatial gene expression patterns during the early stage of maize endosperm development, the gene expression levels at each stage of endosperm development in SD609 and HS68 were classified into five categories based on their FPKM values . The higse1; GRMZM5G842214), which is upstream of the starch metabolism pathway, was only detected at 5 DAP in HS68. However, previous genetic studies have uncovered that se1 is a recessive modifier of su1 that leads to a higher sugar content and an increased kernel moisture for longer post-harvest periods  ≥1 or ≤-1 and FDR ≤ 0.05. Of these, 1,193 DEGs were obtained from the comparison between SD609 and HS68 at the various developmental stages, 7,813 DEGs were consistently expressed in SD609 and HS68 at the different developmental stages, and 4,914 and 2,002 DEGs were DEGs that were only detected in SD609 and HS68, respectively, and are thus considered material-specific DEGs  of the shared DEGs revealed that the gene sets of most clusters were involved in the regulation of system development, reproductive process, and multicellular organismal development  of the genes in the 10 modules had a higher degree of connection and could thus be identified as hub genes for further study . A functAP2/ERF, ARF, bHLH, MYB, WRKY, NAC, bZIP, and GRAS) have been reported to play roles in cell development and the synthesis and accumulation of starch in maize, rice, hulless barley, Arabidopsis, and other plants  was identified as a hub gene in the Grey_60 module, and this gene is mainly involved in the modification of excessively branched chains or the removal of improper branches of amylopectin formed by branching enzymes to maintain the cluster structure of amylopectin. More remarkably, beta-glucosidase 18 and aldose 1-epimerase  were also found in the Grey_60 module and are mainly related to carbohydrate transport and metabolism  presented in a previous study  mutant, and an experiment involving mutations in the amylose extender (ae1.2) also showed that SSI, SSIIa, SBEI and SBEIIb form another multiple-enzyme complex  >SD609 (27.70%) >B73 (25.16%) . The com complex . In part complex .GRMZM2G421033), a member of the AP2/EREBP TF family that positively modulates the starch biosynthetic gene SSIIIa via the synergistic effect of sucrose and ABA, exhibited two transition points (with the upregulated-downregulated-upregulated pattern) in SD609 and HS68 (GRMZM2G023872) belongs to the GRAS TF family and can reduce fractions of long-branched starch chains, and its overexpression leads to the formation of a chalky region in the ventral endosperm with a decreased starch content. In addition, compared with wild-type plants, GRAS20-transgenic seeds exhibit an altered starch granule morphology, which leads to defective agronomic characteristics  to regulate starch synthesis, which is in line with the results of a previous study (O2 might have been replaced by other bZIP TF(s) members because five bZIP TFs were detected in the core gene modules of starch synthesis (Table S11). However, the results of the analysis of cis-regulatory elements in the promoter regions of core genes of starch synthesis indicate that the first possibility is more likely because an O2-binding site was found in the vast majority of core genes of starch synthesis  or mRNA regulatory factor(s) and thereby affect the functions of the core genes involved in starch synthesis and zein genes. Nonetheless, the detailed regulatory mechanism through which zein proteins affect amylose/amylopectin biosynthesis remains to be determined, but this study provides key transcriptional-level clues that will aid further elucidation of the regulatory relationships between amylose biosynthesis and zein-encoding genes.Zeins are abundant storage proteins in most cereals and constitute an important factor that affects seed quality. According to their structural differences, zeins are subdivided into four subclasses: α-zeins , γ-zeins (10–20%), β-zeins (1–5%) and δ-zeins (1–5%) . In our tic mode . Additioand SBEI , which iIn summary, this study offers essential information for identifying the gene atlas of common and high-amylose maize and further distinguishing the expression patterns of genes in the endosperm of common and high-amylose maize. In addition, this analysis provides new clues for exploring the regulatory networks of starch synthesis and will help improve our understanding of endosperm development and the mechanism underlying the regulation of starch synthesis. It also provides valuable information resources for the breeding of maize materials with different starch contents.10.7717/peerj.7528/supp-1Figure S1The reads at 5, 10, 15 and 20 DAP mapped to maize reference genome sequences are shown from the outside to the inside of the Circos image. The red and green colours represent the normalized read numbers of SD609 and HS68, respectively.Click here for additional data file.10.7717/peerj.7528/supp-2Figure S2(A) The enriched GO terms in the “biological process”, (B) “cellular component”, and (C) “molecular function” categories are shown.Click here for additional data file.10.7717/peerj.7528/supp-3Figure S3A total of 1,193 DEGs were differentially expressed between SD609 and HS68, 7,813 DEGs were consistently expressed in SD609 and HS68 at the different development stages, and 4,914 and 2,002 DEGs were specifically detected in SD609 and HS68, respectively.Click here for additional data file.10.7717/peerj.7528/supp-4Figure S4P values < 0.0001 and FDR < 0.01 are shown.(A) Functional annotation of 1,193 DEGs between SD609 and HS68. (B) Shared biological processes regulated by the material-specific DEGs of SD609 and HS68. (C) Specific biological processes of HS68 that are regulated by the material-specific DEGs of SD609 and HS68. (D) Specific biological processes of SD609 that are regulated by the material-specific DEGs of SD609 and HS68. Only biological processes with Click here for additional data file.10.7717/peerj.7528/supp-5Figure S5P value < 0.0001 and FDR < 0.01 are shown. (B) Functional analysis of coexpression clusters of SD609. (C) Functional analysis of coexpression clusters of HS68. (A) Functional analysis of shared DEGs in the coexpression clusters between SD609 and HS68.Only biological processes with a Click here for additional data file.10.7717/peerj.7528/supp-6Figure S6(A) Twelve clusters were characterized by the fluctuating expression of gene sets at 5, 10, 15 and 20 DAP in SD609. (B) Eleven clusters were characterized by the fluctuating expression of gene sets at 5, 10, 15 and 20 DAP in HS68. The up- and downregulated gene sets are staggered or depicted consecutively during the development of the maize endosperm. The scaled expression levels of the DEGs are provided on the y-axis, the developmental stages are shown on the x-axis, the coloured lines represent the individual gene expression clusters, and the trend in the expression of each gene set is depicted by a black line. “n” represents the number of DEGs.Click here for additional data file.10.7717/peerj.7528/supp-7Figure S7The diagonals show the distribution. The lower left section shows a bivariate scatterplot with a fitting line, and the upper right section shows the correlation coefficient and the significance level.Click here for additional data file.10.7717/peerj.7528/supp-8Table S1Click here for additional data file.10.7717/peerj.7528/supp-9Table S2Click here for additional data file.10.7717/peerj.7528/supp-10Table S3Click here for additional data file.10.7717/peerj.7528/supp-11Table S4Click here for additional data file.10.7717/peerj.7528/supp-12Table S5Click here for additional data file.10.7717/peerj.7528/supp-13Table S6Click here for additional data file.10.7717/peerj.7528/supp-14Table S7Click here for additional data file.10.7717/peerj.7528/supp-15Table S8Click here for additional data file.10.7717/peerj.7528/supp-16Table S9Click here for additional data file.10.7717/peerj.7528/supp-17Table S10Click here for additional data file.


The pasting properties, i.e., peak viscosity and breakdown, of all the starches obtained above were analyzed using a Rapid Visco Analyzer. Furthermore, the gelatinization properties and in vitro digestibility of the representative calcium- and magnesium-fortified starches were tested. The maximum calcium content of the fortified potato starches was as high as 686 ppm with the addition of a high-concentration CaCl2 solution, while the calcium content of the control potato starch was 99 ppm. The magnesium content increased from 89 to 421 ppm by treatment of the potato starch with an MgCl2 solution. Markedly lower values of peak viscosity and breakdown were observed in calcium- and magnesium-fortified potato starches than in the control potato starch. However, the gelatinization temperature and enthalpy as well as resistant starch content of calcium- and magnesium-fortified potato starches were similar to those of the control potato starch. It is concluded that potato starches with altered pasting properties can be easily manufactured by the use of solutions containing high levels of calcium and magnesium.Calcium- and magnesium-fortified potato starches were prepared by immersion in various concentrations of CaCl Small amounts of phosphate monoesters exist in native starch molecules. It has been established that potato starch contains high starch-bound phosphate compared with starches isolated from other plants ,3,4,5,6.et al.  also rep2 and MgCl2 of various concentrations and to measure the pasting properties of all of the starches obtained above using RVA. We assessed the effects of calcium and magnesium enrichment on other starch properties. For this purpose, we analyzed the gelatinization properties of the representative calcium- and magnesium-fortified starches using differential scanning calorimetry (DSC) as well as the in vitro digestibility of the starches.The objective of this study was to prepare calcium- and magnesium-fortified potato starches by immersions of potato starch produced in a local factory in Hokkaido in aqueous solutions of CaClThe content of five minerals—phosphorus, calcium, magnesium, sodium, and potassium—of the control potato starch is shown in 2 aqueous solution. As can be seen in 2 concentration up to 0.1%. In contrast, varying CaCl2 concentrations, from 0.25% to 1% resulted in an almost constant calcium content in the treated starches (640 to 686 ppm). In the RVA test, peak viscosity and breakdown were measured, and the values of peak viscosity and breakdown of the control potato starch were 279 and 169 RVU, respectively. In response to the results of the calcium content of the treated potato starches, peak viscosity and breakdown decreased markedly with the enhancement of CaCl2 concentration up to 0.1%. Similar values of peak viscosity (185 to 193 RVU) and breakdown (72 to 82 RVU) of the treated potato starches were observed with the addition of 0.25% to 1% CaCl2 aqueous solutions. Due to the fact that the control potato starch is lacking in calcium and magnesium, we attempted to prepare calcium- and magnesium-fortified potato starches from the control potato starch and analyzed the pasting properties of these potato starches using RVA. First, 100 g of the control potato starch was treated with different amounts of calcium using 300 mL of CaCl2 aqueous solution. As shown in 2·6H2O concentrations up to 0.2%. Above a 0.5% MgCl2·6H2O concentration, the magnesium content of the treated starch tended to be relatively constant (382 to 421 ppm). Similar to the trend of the magnesium content of the treated potato starches, an increased concentration of MgCl2·6H2O, up to 0.2%, led to a definite decrease in peak viscosity and breakdown. There were no significant differences in peak viscosity (197 to 205 RVU) and breakdown (76 to 84 RVU) of the treated potato starches at treatment at concentrations of 0.5% to 2% MgCl2·6H2O. Next, 100 g of the control potato starch was treated with different amounts of magnesium by use of 300 mL of an MgCl2 concentration for the calcium-fortified starch; and (ii) immersion in 1% MgCl2·6H2O concentration for the magnesium-fortified starch. Thus, we established an effective way to prepare calcium- and magnesium-fortified potato starches with drastically decreased values of peak viscosity and breakdown.From the results obtained here, we set up standard conditions for the preparation of calcium- and magnesium-fortified potato starches as follows: (i) immersion in 0.5% CaCl2 and MgCl2 aqueous solutions, respectively.We attempted to examine the properties of calcium- and magnesium-fortified potato starches obtained under the standard conditions mentioned above and to compare them with those of the control potato starch. First, we compared the mineral composition of the calcium- and magnesium-fortified potato starches with that of the control potato starch. As shown in Thermal properties were measured by DSC, and the results of the calcium- and magnesium-fortified potato starches as well as the control potato starch are presented in To determine resistant starch (RS) content, each raw starch was treated with pancreatic α-amylase and amyloglucosidase for 16 h at 37 °C. As can be clearly seen from et al. [2 solution, and distilled water, which is time consuming and not necessarily suitable for the industrial production of calcium-fortified potato starches. Wiesenborn et al. [et al. [2 and saturated Mg(OH)2 solution in a volume ratio of 1:1 resulted in an increased magnesium content (322.6 ppm). However, Fortuna et al. [The dietary roles of calcium and magnesium for health promotion and disease prevention have been widely accepted. As starch is widely used in food production systems and contributes largely to the textural properties of the foods, the fortification of starches with calcium and magnesium would be a promising technology. Until now, modified starches, which are highly capable of binding metal elements, were used as carriers of calcium and magnesium, important mineral elements. Calcium fortification was reported for hydroxypropyl starches ,22, and et al. ; howevern et al.  suggeste [et al. , treatmea et al.  did not 2 and MgCl2 aqueous solutions, respectively. The calcium- and magnesium-fortified potato starches obtained in this study had more than six times higher calcium content (maximum 686 ppm) and over four times higher magnesium content (maximum 421 ppm), respectively, than did the control potato starch. On a molar basis, the ratios of calcium and magnesium to phosphorus were approximately two-thirds for calcium- and magnesium-fortified potato starches, respectively. Similar trends were observed when three potato starches with different phosphorus contents were fortified with calcium [i.e., peak viscosity and breakdown, were in agreement with the previous data mentioned above. DSC has been widely used to analyze starch gelatinization, but there has been limited information regarding the contribution of calcium and magnesium of potato starch to the gelatinization properties measured by DSC. According to the recent study of Fortuna et al. [et al. [In this article, we have described a convenient and practical method for preparing calcium- and magnesium-fortified potato starches from factory-made potato starch by immersions in various concentrations of CaCl calcium . Starch  calcium  and magn calcium . By comp calcium ,18 and s calcium  resulteda et al. . The det maximum 86 ppm ana et al. ,26,27. S [et al. , reportiThe present study has revealed an effective way to prepare calcium- and magnesium-fortified potato starches with drastically decreased values of peak viscosity and breakdown using potato starch produced at a local factory in Hokkaido. The fortified potato starches have extremely large amounts of RS similar to the control starch. From the viewpoint of both potential health benefits and functional properties, calcium- and magnesium-fortified potato starches are value-added food materials. Our findings would expand the utilization of the potato starch produced in Hokkaido. Application of the fortified potato starches to food production is now in progress.2) and magnesium chloride hexahydrate (MgCl2·6H2O) were purchased from Wako Pure Chemical Industries, Ltd. . Potato starch obtained from Toubu Tokachi Noukouren Starch Factory  was used as the control potato starch in this study. Calcium chloride, anhydrous, (CaCl2 solution (300 mL) and held for 3 h. The supernatant was discarded, and the remaining starch pellet was washed twice with distilled water, and then dried at 20 °C. To prepare the magnesium-fortified potato starch, control potato starch (100 g) was suspended in a 0.02% to 2% MgCl2·6H2O solution (300 mL) and held for 3 h. The supernatant was discarded, and the remaining starch pellet was washed twice with distilled water and then dried at 20 °C. The obtained starch samples were stored at 4 °C until analysis.To prepare the calcium-fortified potato starch, the control potato starch (100 g) was suspended in a 0.005% to 1% CaClet al. [et al. [For all starch samples examined, the RVA paste viscosity at 4% starch suspension  was determined as previously reported . The calet al. , while tet al. . DSC the [et al. . The RS  [et al. . Measure2 and among various concentrations of MgCl2 aqueous solutions. Additionally, DSC thermal parameters and RS content averages were computed, and the Duncan's multiple range tests were conducted to measure variations in the DSC thermal parameters and RS content among the representative calcium- and magnesium-fortified potato starches and the control potato starch. Significance was defined at p < 0.05.The RVA paste viscosity averages were computed, and the Duncan’s multiple range tests were conducted to measure variations in the RVA paste viscosity among various concentrations of CaCl2 and MgCl2 aqueous solutions, respectively. As a result, the potassium in the control potato starch was replaced by calcium and magnesium with these treatments. Calcium- and magnesium-fortified potato starches exhibited manifestly lower peak viscosity and breakdown than did the control potato starch. In contrast, gelatinization temperature and enthalpy of calcium- and magnesium-fortified potato starches were similar to those of the control potato starch. High RS content (around 94%) was observed in the calcium- and magnesium-fortified potato starches, and no significant difference in RS content was found as a result of calcium- and magnesium fortification of the control potato starch. Calcium- and magnesium-fortified potato starches appear to be important food sources for sources of calcium and magnesium, respectively. In addition, they possess good viscosity stability and high amounts of RS, which has received much attention for its health benefits. Our experimental results should provide useful information for the food industry to make better use of potato starch.Calcium- and magnesium-fortified potato starches were successfully prepared by immersion in CaCl


Siempre imaginé que el Paraíso sería algún tipo de biblioteca.I have always imagined that Paradise will be a kind of library.Jorge Luis Borges (1899 - 1986)The Journal of Experimental Orthopaedics was launched in late 2013 by the European Society of Sports Traumatology, Knee Surgery & Arthroscopy (ESSKA), serving to bridge the gap between orthopaedic basic science and clinical relevance. I was provided with the good fortune to envision and serve as the founding Editor-in-Chief of the Journal of Experimental Orthopaedics. Leading the Journal has been an extremely rewarding and memorable phase of my professional career.From early on, the vision of a new Journal was supported and mentored by creative leaders of the ESSKA, among which Lars Engebretsen, João Espregueira-Mendes, Romain Seil, Niek van Dijk, Matteo Denti, David Dejour, Jacques Menetrey and many others. The idea took on a real form on March 5th, 2011 in Salon 3 of the Villa Sarasin  in Le Grand-Saconnex near Geneva in Switzerland at an ESSKA Board Meeting. There, it was decided to proceed with the launch of a new journal that would be the official basic science journal of ESSKA, complementing the more clinical Knee Surgery, Sports Traumatology, Arthroscopy (KSSTA) journal. The Journal of Experimental Orthopaedics was designed as a unique biomedical journal with a surgical background, aiming to merge the rigor of basic science with the art of orthopaedic surgery Madry, .Our 100th article appeared in Pubmed on 4 September 2017, and at the time of this Editorial, nearly 190 articles have been published. Successfully attracting good quality manuscripts, often with the help of active ESSKA committees, significantly promoted the journal’s reputation. The Journal of Experimental Orthopaedics guarantees a rigorous, objective, and timely peer review process. Editorial decisions are solely based on scientific integrity and merit, not profit or scientific fashion. Although an evolution of the journal is inevitable, these fundamental principles shall never change for the Journal of Experimental Orthopaedics to retain its stature. In a recent Clarivate analysis, the journal would be placed in the second quartile (Q2) and therefore in the upper half of journals for the category “Orthopaedics - Sci” category in Web of Science. The open access model allowed for a remarkable dissemination: for example a study on determining bone tunnel sizes in anterior cruciate ligament reconstruction has been accessed about 34.500 times since its publication in June 2014  famously quoted: “Life is a journey, not a destination.” It was not an easy decision for me to make a move to a newly introduced journal, and although I will be taking up a new assignment as Editor-in-Chief of Osteoarthritic and Cartilage Open, I will continue to support the Journal of Experimental Orthopaedics to the best of my ability. Please join me in welcoming Stefano Zaffagnini in his new capacity as Editor, and I am sure that Stefano with his superb clinical and scientific expertise brings excellent credentials that will continue to provide the dedication, enthusiasm, and creativity for the continued stewardship of the journal.At the same time, I would like to express my sincere appreciation to the ESSKA leadership who I thank for giving me the editorial responsibility to establish the Journal of Experimental Orthopaedics. I am very grateful for the support of our excellent Editorial Board and distinguished Board of Trustees, among which scientists serving as presidents of universities or international organizations such as ESSKA, the ORS, and the ICRS, and to other Editors-in-Chief, among which Jón Karlsson and Ejnar Eriksson of KSSTA, Bruce Reider of The American Journal of Sports Medicine, Farshid Guilak of the Journal of Biomechanics, Detlev Ganten of the Journal of Molecular Medicine, and Rocky Tuan of Stem Cell Research & Therapy. I have highly enjoyed working very effectively with our Editorial Office in Luxembourg served by a tireless staff of dedicated professionals, and Gabriele Schröder in her position as Editorial Director at SpringerNature, and I would like to thank them for their constant effort. Finally yet importantly, I thank our authors, reviewers, and readers for ensuring the success of the Journal of Experimental Orthopaedics.I wish you all the best.Sincerely,Henning Madry


PLOS Computational Biology has published key insights that advance our understanding of biology and medicine—advances enabled by developments in computation and quantitative analyses. As an example, a recent initiative across the journals PLOS Medicine, PLOS ONE, and PLOS Computational Biology [Machine Learning in Health and Biomedicine. The breadth of research published in PLOS Computational Biology at this intersection of machine learning and health and biology was incredible, from the use of machine learning analysis to delineate biomarkers for soft tissue sarcomas [Escherichia coli from pan-genome data [Scientific advances are frequently catalyzed by exploring the intersection of disciplines. From its inception,  Biology  resultedsarcomas  to the pome data . We’re oTargeted Anticancer Therapies and Precision Medicine call for papers jointly with PLOS ONE and PLOS Computational Biology [Many more cross-journal initiatives are in the works, exploring how disparate disciplines can be brought together to tackle seemingly intransigent problems with unique perspectives. Just launched is a  Biology . With ne Biology  and an i Biology , there iPLOS Computational Biology. This journal, like the other PLOS community journals, is led by more than 160 practicing scientists with a variety of disciplinary backgrounds. All papers submitted to the journal are evaluated by multiple scientists through the peer review process and by teams of scientists at the editorial stage. It is with this integration of these different opinions of scientists from different subdisciplines of computational biology that we try to identify and support the development and publication of outstanding science. This journal thus embraces the wisdom of crowds in the practice of science [As we do in these scientific ventures, so we do in managing the activity of  science  as the fPLOS Computational Biology is led by a “wisdom of crowds” structure, with co-editors in chief, a deputy editor-in-chief, deputy editors, associate editors, and an advisory board all bringing different perspectives to advance the field. Ruth Nussinov has been a leader of this journal for many years, recently leading as a co-editor in chief. She has been a pioneer in computational biology, recently recognized with the 2018 International Society for Computational Biology (ISCB) Accomplishment by a Senior Scientist Award [


Complete necrosis of the graft ureter is a rare but serious complication following kidney transplant. In a patient with antiphospholipid syndrome, a combination of factors such as arterial thromboembolism, hematoma formation, and surgical collateral damage can cause ischemia of the graft ureter. Preoperative optimization of disease activity and coagulation with meticulous preservation of ureteric perfusion may help in prevention. Primary antiphospholipid syndrome was diagnosed 2 years prior to renal transplantation when he developed recurrent episodes of thrombosis of the arteriovenous fistula and neck veins, for which he was started on warfarin. Anticoagulation was optimized prior to surgery by withholding warfarin 5 days before surgery while bridging with heparin. During the early postoperative period (first postoperative week), he developed a peri‐renal hematoma (ultrasonography 13 cm × 7 cm). Noncontrast computed tomography scan detected a homogenous fluid collection posterior to the transplanted kidney which extended superiorly up to the right subhepatic area and inferiorly into the pelvis, displacing the bladder to the left  including lupus anticoagulant and anticardiolipin antibodies, are directed against phospholipid‐binding proteins. It is clinically characterized by an increased tendency for recurrent vascular thromboembolism involving arteries and veins.Management of defects in the graft ureter depends on the extent and severity. Smaller defects such as a simple anastomotic leak may require primary suture of the leaking segment over a double J stent insertion or a reimplantation of the ureter. However, complete necrosis due to ischemia requires total replacement of the graft ureter and in such cases, exploration and definitive treatment should not be delayed.The utilization of the physiologic anti‐reflux mechanism of the bladder is a known advantage in this technique. Furthermore, it is relatively easy to perform and if carefully dissected, the blood supply of the native ureter could be preserved. This procedure requires a normal native ureter. If the native ureter is nonfunctional or absent due to previous surgeries or abnormally short, other alternative techniques such as direct vesicopyelostomy may be performed.However, in rare instances, difficulty in mobilizing the bladder or the graft kidney could make the procedure technically difficult. In such cases, a Boari flap is a useful alternative.However, vesicopyelostomy may result in considerable vesico‐ureteric reflux. Therefore, reflux of urine into the graft renal pelvis may occur resulting in complications such as graft failure or recurrent infections. These infections are difficult to control due to the immunocompromised state of the host. Furthermore, it is shown that reflux is less common in patients with Boari flap compared with direct vesicopyelostomy.Our patient with antiphospholipid syndrome developed a hematoma in the early postoperative period, which was managed conservatively. Later, he developed a complete necrosis of the graft ureter and a large urinoma. Multiple factors may have contributed to the compromised blood supply of the graft ureter, which is solely derived from the graft renal artery. Careful attention to perioperative optimization, meticulous haemostasis and preservation of peri‐ureteric and pelvi‐ureteric adipose tissue with the contained vasculature may help to prevent this complication.4Ischemic sloughing of the entire ureter following renal transplant is fortunately a rare occurrence and is generally attributed to the compromised ureteric blood supply. In a patient with antiphospholipid syndrome, complete necrosis could result due to a combination of factors such as arterial thromboembolism, hemorrhage and surgical collateral damage leading to small vessel occlusion and ischemia. Preservation of graft ureteric blood supply with meticulous haemostasis may help to prevent this complication. Furthermore, following an early postoperative hematoma, possibility of a subsequent necrosis of the graft ureter should be considered and close monitoring and follow up becomes mandatory.None declared.DMHF, UJ, and BADR: contributed to the collection of information and writing of the manuscript. WRDF and SASG: contributed to writing and final approval of the manuscript.Informed written consent was obtained from the patient for publication.


Microbiology, Journal of General Virology, Journal of Medical Microbiology, International Journal of Systematic and Evolutionary Microbiology, Microbial Genomics and Access Microbiology) are committed to serving the microbiology community by providing access to read and publish the broadest range of papers in our fields. We are continually reviewing the nature and scope of our journals and considering ways in which we can serve our authors, our readership and the society. One of the areas of concern to our community has been the improper use of Journal Impact Factors in assessing the quality or impact of science and scientists. There has been a long debate over appropriate ways to monitor the quality of science that is funded and published and while there is no consensus on the most effective or efficient methods, it is clear that judging the quality of individual pieces of work based on the impact factor of the journal in which they are published is not useful or appropriate.The Editors, Senior Editors and Editors-in-Chief of the Society journals , 10.1099/mic.0.000692) to provide a different and, we hope, more relevant means of assessing and accessing information on the manuscript level. As an extension of this, the Society has recently become a signatory to DORA, the San Francisco Declaration on Research Assessment. DORA challenges the role played by the Impact Factor and promotes the need to improve the ways in which the outputs of scholarly research are evaluated; it promotes the assessment of research on its own merits rather than on the basis of the journal in which the research is published.The Microbiology Society journals have been using a variety of alternative metrics, mostly focused on individual papers  as another step towards eliminating misleading metrics and improving scientific discourse and dissemination.’Tanya Parish. ‘We removed the Impact Factor from Journal of Medical Microbiology has also removed the Impact Factor from our home page. We support the Society’s decision to fight against the artificiality of the Impact Factor and reject its use that does more disservice than service to the scientists in this “publish or perish” era.’Kalai Mathee and Norman Fry. ‘The Journal of General Virology believes that Impact Factors are not a reliable or accurate indication of the quality of the science published in a journal. Now that accurate metrics on individual articles can be easily accessed, we believe that these provide a better way to assess both quality and impact. We therefore wholeheartedly support the Society’s decision to sign the DORA agreement.’Mark Harris and Paul Duprex. ‘The International Journal of Systematic and Evolutionary Microbiology is the leading journal for the publication of novel microbial taxa. We applaud the decision of the Society to sign the DORA agreement and have also decided to remove the Impact Factor from our home page. We believe it does not reflect the quality of the work published.’Martha E. Trujillo. ‘The Microbial Genomics to record altmetrics for all our articles. There has been and almost certainly will continue to be intense debate around Impact Factor and its impact on the future direction of our field and those within it. We need to find new ways that are both practical and informative and so we welcome and support this initiative by the Society to sign up to DORA.’Nick Thomson and Stephen Bentley. ‘We purposely set up