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Showing papers by "DSM published in 2021"


Journal ArticleDOI
TL;DR: A review of recent, emerging, and anticipated trends in probiotic and prebiotic science, and a vision for broad areas of developing influence in the field can be found in this article.

191 citations


Journal ArticleDOI
TL;DR: In this paper, the authors highlight the unique science opportunities using spectral distortions of the cosmic microwave background (CMB) for further understanding of inflation, recombination, reionization and structure formation as well as dark matter and particle physics.
Abstract: This Voyage 2050 paper highlights the unique science opportunities using spectral distortions of the cosmic microwave background (CMB). CMB spectral distortions probe many processes throughout the history of the Universe, delivering novel information that complements past, present and future efforts with CMB anisotropy and large-scale structure studies. Precision spectroscopy, possible with existing technology, would not only provide key tests for processes expected within the cosmological standard model but also open an enormous discovery space to new physics. This offers unique scientific opportunities for furthering our understanding of inflation, recombination, reionization and structure formation as well as dark matter and particle physics. A dedicated experimental approach could open this new window to the early Universe in the decades to come, allowing us to turn the long-standing upper distortion limits obtained with COBE/FIRAS some 25 years ago into clear detections of the expected standard distortion signals and also challenge our current understanding of the laws of nature.

63 citations


Journal ArticleDOI
TL;DR: In this paper, the authors assess and rank human milk oligosaccharides (HMOs) from healthy mothers throughout lactation at a global level, using data from pooled (secretor and non-secretor) human milk samples.
Abstract: Human milk oligosaccharides (HMOs) are non-digestible and structurally diverse complex carbohydrates that are highly abundant in human milk. To date, more than 200 different HMO structures have been identified. Their concentrations in human milk vary according to various factors such as lactation period, mother’s genetic secretor status, and length of gestation (term or preterm). The objective of this review is to assess and rank HMO concentrations from healthy mothers throughout lactation at a global level. To this aim, published data from pooled (secretor and non-secretor) human milk samples were used. When samples were reported as secretor or non-secretor, means were converted to a pooled level, using the reported mean of approximately 80/20% secretor/non-secretor frequency in the global population. This approach provides an estimate of HMO concentrations in the milk of an average, healthy mother independent of secretor status. Mean concentrations of HMOs were extracted and categorized by pre-defined lactation periods of colostrum (0–5 days), transitional milk (6–14 days), mature milk (15–90 days), and late milk (>90 days). Further categorizations were made by gestational length at birth, mother’s ethnicity, and analytical methodology. Data were excluded if they were from preterm milk, unknown sample size and mothers with any known disease status. A total of 57 peer-reviewed articles reporting individual HMO concentrations published between 1996 and 2020 were included in the review. Pooled HMO means reported from 31 countries were analyzed. In addition to individual HMO concentrations, 12 articles reporting total HMO concentrations were also analyzed as a basis for relative HMO abundance. Total HMOs were found as 17.7 g/L in colostrum, 13.3 g/L in transitional milk, and 11.3 g/L in mature milk. The results show that HMO concentrations differ largely for each individual HMO and vary with lactation stages. For instance, while 2′-FL significantly decreased from colostrum (3.18 g/L ± 0.9) to late milk (1.64 g/L ± 0.67), 3-FL showed a significant increase from colostrum (0.37 g/L ± 0.1) to late milk (0.92 g/L ± 0.5). Although pooled human milk contains a diverse HMO profile with more than 200 structures identified, the top 10 individual HMOs make up over 70% of total HMO concentration. In mature pooled human milk, the top 15 HMOs in decreasing order of magnitude are 2′-FL, LNDFH-I (DFLNT), LNFP-I, LNFP-II, LNT, 3-FL, 6′-SL, DSLNT, LNnT, DFL (LDFT), FDS-LNH, LNFP-III, 3′-SL, LST c, and TF-LNH.

53 citations


Journal ArticleDOI
TL;DR: In this paper, the possibility of regulating gut microbiota to reverse these perturbations by developing a regulatory system was discussed, where the authors showed that an increasing body of evidence has shown that gut microbiota imbalances are linked to diseases.
Abstract: An increasing body of evidence has shown that gut microbiota imbalances are linked to diseases. Currently, the possibility of regulating gut microbiota to reverse these perturbations by developing ...

46 citations


Journal ArticleDOI
TL;DR: The effects of vitamins on the gut microbiome and related gastrointestinal health, based on in vitro, animal and human studies, are discussed in this article, where some vitamins, when provided in large doses or when delivered to the large intestine, have been shown to beneficially modulate the Gut microbiome by increasing the abundance of presumed commensals (vitamins A, B2, D, E, and beta-carotene).

46 citations


Journal ArticleDOI
TL;DR: In this article, the spacing between the donor and the acceptor materials (DA spacing) was shown to be the origin of the too-fast nonradiative decay of charge carriers in organic solar cells.
Abstract: The high voltage losses ([Formula: see text]), originating from inevitable electron-phonon coupling in organic materials, limit the power conversion efficiency of organic solar cells to lower values than that of inorganic or perovskite solar cells. In this work, we demonstrate that this [Formula: see text] can in fact be suppressed by controlling the spacing between the donor (D) and the acceptor (A) materials (DA spacing). We show that in typical organic solar cells, the DA spacing is generally too small, being the origin of the too-fast non-radiative decay of charge carriers ([Formula: see text]), and it can be increased by engineering the non-conjugated groups, i.e., alkyl chain spacers in single component DA systems and side chains in high-efficiency bulk-heterojunction systems. Increasing DA spacing allows us to realize significantly reduced [Formula: see text] and improved device voltage. This points out a new research direction for breaking the performance bottleneck of organic solar cells.

36 citations


Journal ArticleDOI
Peter Van Dael1
TL;DR: The role of n-3 polyunsaturated fatty acids (n-3 PUFAs) on brain health, in particular neurodegenerative disorders and depression, is reviewed in this paper.
Abstract: Long-chain (LC) n-3 polyunsaturated fatty acids (n-3 PUFAs), in particular docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are nutrients involved in many metabolic and physiological processes, and are referred to as n-3 LCPUFA. They have been extensively studied for their effects in human nutrition and health. This paper provides an overview on metabolism, sources, dietary intake, and status of n-3 LCPUFA. A summary of the dietary recommendations for n-3 LCPUFAs for different age groups as well as specific physiological conditions is provided. Evidence for n-3 LCPUFA in cardiovascular diseases, including new studies, is reviewed. Expert recommendations generally support a beneficial effect of n-3 LCPUFA on cardiovascular health and recommend a daily intake of 500 mg as DHA and EPA, or 1-2 servings of fish per week. The role of n-3 LCPUFA on brain health, in particular neurodegenerative disorders and depression, is reviewed. The evidence for beneficial effects of n-3 LCPUFA on neurodegenerative disorders is non-conclusive despite mechanistic support and observational data. Hence, no definite n-3 LCPUFA expert recommendations are made. Data for the beneficial effect of n-3 LCPUFA on depression are generally compelling. Expert recommendations have been established: 200-300 mg/day for depression; up to 1-2 g/day for major depressive disorder. Recent studies support a beneficial role of n-3 LCPUFAs in reducing the risk for premature birth, with a daily intake of 600-800 mg of DHA during pregnancy. Finally, international experts recently reviewed the scientific evidence on DHA and arachidonic acid (ARA) in infant nutrition and concluded that the totality of data support that infant and follow-on formulas should provide both DHA and ARA at levels similar to those in breast milk. In conclusion, the available scientific data support that dietary recommendations for n-3 LCPUFA should be established for the general population and for subjects with specific physiological conditions.

32 citations


Journal ArticleDOI
TL;DR: In this article, a comprehensive and exhaustive pathogenetic paradigm in ASD, viewed not just as a theoretical issue, but as a tool to provide suggestions for effective preventive strategies and personalized, dynamic (from womb to adulthood), systemic, and interdisciplinary healthcare approach is presented.
Abstract: The wide spectrum of unique needs and strengths of Autism Spectrum Disorders (ASD) is a challenge for the worldwide healthcare system. With the plethora of information from research, a common thread is required to conceptualize an exhaustive pathogenetic paradigm. The epidemiological and clinical findings in ASD cannot be explained by the traditional linear genetic model, hence the need to move towards a more fluid conception, integrating genetics, environment, and epigenetics as a whole. The embryo-fetal period and the first two years of life (the so-called ‘First 1000 Days’) are the crucial time window for neurodevelopment. In particular, the interplay and the vicious loop between immune activation, gut dysbiosis, and mitochondrial impairment/oxidative stress significantly affects neurodevelopment during pregnancy and undermines the health of ASD people throughout life. Consequently, the most effective intervention in ASD is expected by primary prevention aimed at pregnancy and at early control of the main effector molecular pathways. We will reason here on a comprehensive and exhaustive pathogenetic paradigm in ASD, viewed not just as a theoretical issue, but as a tool to provide suggestions for effective preventive strategies and personalized, dynamic (from womb to adulthood), systemic, and interdisciplinary healthcare approach.

30 citations


Journal ArticleDOI
TL;DR: This review describes recent applications of food metabolomics from fork to farm and focuses on the opportunities these bring to continue food innovation and support the shift to plant-based foods.

29 citations


Journal ArticleDOI
TL;DR: Both high number and blockwise distribution of non-esterified GalA in pectins are responsible for the anti-inflammatory effects via inhibition of TLR2-1.

27 citations


Journal ArticleDOI
TL;DR: There is a positive effect of omega-3 LC PUFA supplementation on overall body muscle mass and strength, and small study size and heterogeneity limit the applicability of these findings for sarcopenia prevention.
Abstract: Summary Background & aims Sarcopenia is characterized by the progressive loss of skeletal muscle mass and function, which reduces mobility and quality of life. Risk factors for sarcopenia include advanced age, physical inactivity, obesity, and chronic diseases such as cancer or rheumatoid arthritis. Omega-3 long chain polyunsaturated fatty acids (LC PUFAs) might be associated with a reduction in risk of sarcopenia due to their anti-inflammatory effects. Methods We conducted a systematic review and meta-analysis to quantify the effects of omega-3 LC PUFAs on muscle mass, volume and function parameters. The National Library of Medicine's MEDLINE/PubMed database was searched on 9th October 2020 for randomized controlled trials that used omega-3 LC PUFAs as an intervention with muscle-related endpoints. A snowballing search to identify additional studies was completed on 23rd April 2021. The meta-analysis was conducted using meta-essentials worksheet 3. Bias was assessed using the Jadad scale. Results 123 studies were identified with the systematic searches. Most studies were performed in disease populations, such as cancer or chronic obstructive pulmonary disease (COPD), or in healthy individuals after a fatiguing exercise bout. The endpoints lean body mass, skeletal muscle mass, mid-arm muscle circumference, handgrip strength, quadriceps maximal voluntary capacity (MVC), and 1-repetition maximum chest press were selected for meta-analysis based on the number of available studies; thus 66 studies were included in the quantitative synthesis. Using a random effects model and 2-tailed p-value, there was a significant relationship in favor of omega-3 LC PUFA supplementation for lean body mass (effect size 0.27, 95%CI 0.04 to 0.51), skeletal muscle mass (effect size 0.31, 95%CI 0.01 to 0.60) and quadriceps MVC (effect size 0.47, 95%CI 0.02 to 0.93). Conclusion The results indicate that there is a positive effect of omega-3 LC PUFA supplementation on overall body muscle mass and strength. Small study size and heterogeneity limit the applicability of these findings for sarcopenia prevention. Larger trials in populations at risk of sarcopenia would strengthen the evidence base.

Journal ArticleDOI
TL;DR: This work reviews current and emerging detection methods in liquid chromatography with the aim of identifying detectors, which can be applied to the quantitative analysis of complex polymers.
Abstract: Accurate quantification of polymer distributions is one of the main challenges in polymer analysis by liquid chromatography. The response of contemporary detectors is typically influenced by compositional features such as molecular weight, chain composition, end groups, and branching. This renders the accurate quantification of complex polymers of which there are no standards available, extremely challenging. Moreover, any (programmed) change in mobile-phase composition may further limit the applicability of detection techniques. Current methods often rely on refractive index detection, which is not accurate when dealing with complex samples as the refractive-index increment is often unknown. We review current and emerging detection methods in liquid chromatography with the aim of identifying detectors, which can be applied to the quantitative analysis of complex polymers.

Journal ArticleDOI
Elodie Bacou1, Carrie L Walk1, Sebastien Rider1, Gilberto Litta1, Estefania Perez-Calvo1 
TL;DR: A better understanding of the oxidative distress mechanisms associated with dietary stressors allows for improved understanding and evaluation of feed additives as mitigators of oxidative distress.
Abstract: The redox system is essential for maintaining cellular homeostasis. When redox homeostasis is disrupted through an increase of reactive oxygen species or a decrease of antioxidants, oxidative distress occurs resulting in multiple tissue and systemic responses and damage. Poultry, swine and fish, raised in commercial conditions, are exposed to different stressors that can affect their productivity. Some dietary stressors can generate oxidative distress and alter the health status and subsequent productive performance of commercial farm animals. For several years, researchers used different dietary stressors to describe the multiple and detrimental effects of oxidative distress in animals. Some of these dietary challenge models, including oxidized fats and oils, exposure to excess heavy metals, soybean meal, protein or amino acids, and feeding diets contaminated with mycotoxins are discussed in this review. A better understanding of the oxidative distress mechanisms associated with dietary stressors allows for improved understanding and evaluation of feed additives as mitigators of oxidative distress.

Journal ArticleDOI
TL;DR: In this article, a collection of 96 genetic parts, characterized in Penicillium or Aspergillus species, that are compatible and interchangeable with the Modular Cloning system are presented.
Abstract: Filamentous fungi are highly productive cell factories, often used in industry for the production of enzymes and small bioactive compounds. Recent years have seen an increasing number of synthetic-biology-based applications in fungi, emphasizing the need for a synthetic biology toolkit for these organisms. Here we present a collection of 96 genetic parts, characterized in Penicillium or Aspergillus species, that are compatible and interchangeable with the Modular Cloning system. The toolkit contains natural and synthetic promoters (constitutive and inducible), terminators, fluorescent reporters, and selection markers. Furthermore, there are regulatory and DNA-binding domains of transcriptional regulators and components for implementing different CRISPR-based technologies. Genetic parts can be assembled into complex multipartite assemblies and delivered through genomic integration or expressed from an AMA1-sequence-based, fungal-replicating shuttle vector. With this toolkit, synthetic transcription units with established promoters, fusion proteins, or synthetic transcriptional regulation devices can be more rapidly assembled in a standardized and modular manner for novel fungal cell factories.

Journal ArticleDOI
Jérôme Bucalossi1
TL;DR: In this article, a set of ITER-grade plasma facing unit prototypes was integrated into the inertially cooled W coated startup lower divertor, with a discharge time of about one minute.
Abstract: WEST is a MA class superconducting, actively cooled, full tungsten (W) tokamak, designed to operate in long pulses up to 1000 s. In support of ITER operation and DEMO conceptual activities, key missions of WEST are: i) qualification of high heat flux plasma-facing components in integrating both technological and physics aspects in relevant heat and particle exhaust conditions, particularly for the tungsten monoblocks foreseen in ITER divertor; ii) integrated steady-state operation at high confinement, with a focus on power exhaust issues. During the phase 1 of operation (2017-2020), a set of ITER-grade plasma facing unit prototypes was integrated into the inertially cooled W coated startup lower divertor. Up to 8.8 MW of RF power has been coupled to the plasma and divertor heat flux of up to 6 MW/m2 were reached. Long pulse operation was started, using the upper actively cooled divertor, with a discharge of about one minute achieved. This paper gives an overview of the results achieved in phase 1. Perspectives for phase 2, operating with the full capability of the device with the complete ITER-grade actively cooled lower divertor, are also evoked.

Journal ArticleDOI
TL;DR: In this paper, the authors investigated how dietary manipulation from birth influences growth, methane production, and gastrointestinal microbial ecology of Holstein and Montbeliarde calves. And they found that despite modest modifications to the abundance of rumen microbes, the reductive effect of 3-NOP on methane production persisted following cessation of the treatment period, perhaps indicating a differentiation of the ruminal microbial ecosystem or a host response triggered by the treatment in early development phase.
Abstract: Recent evidence suggests that changes in microbial colonization of the rumen prior to weaning may imprint the rumen microbiome and impact phenotypes later in life. We investigated how dietary manipulation from birth influences growth, methane production, and gastrointestinal microbial ecology. At birth, 18 female Holstein and Montbeliarde calves were randomly assigned to either treatment or control (CONT). Treatment was 3-nitrooxypropanol (3-NOP), an investigational anti-methanogenic compound that was administered daily from birth until three weeks post-weaning (week 14). Samples of rumen fluid and faecal content were collected at weeks 1, 4, 11, 14, 23, and 60 of life. Calves were tested for methane emissions using the GreenFeed system during the post-weaning period (week 11–23 and week 56–60 of life). Calf physiological parameters (BW, ADG and individual VFA) were similar across groups throughout the trial. Treated calves showed a persistent reduction in methane emissions (g CH4/d) throughout the post-weaning period up to at least 1 year of life, despite treatment ceasing three weeks post-weaning. Similarly, despite variability in the abundance of individual taxa across weeks, the rumen bacterial, archaeal and fungal structure differed between CONT and 3-NOP calves across all weeks, as visualised using sparse-PLS-DA. Similar separation was also observed in the faecal bacterial community. Interestingly, despite modest modifications to the abundance of rumen microbes, the reductive effect of 3-NOP on methane production persisted following cessation of the treatment period, perhaps indicating a differentiation of the ruminal microbial ecosystem or a host response triggered by the treatment in the early development phase.

Journal ArticleDOI
N. E. Ward1
TL;DR: A broad scope of enzymatic activity in customized mixes can more effectively target the resilient NSP construct of cereal grains in commercial poultry diets, particularly those in corn-based feeds.

Journal ArticleDOI
TL;DR: 3-NOP decreased enteric methane daily emission, yield, and intensity without affecting dry matter intake and milk yield, but increased milk fat in high-producing dairy cows.

Journal ArticleDOI
TL;DR: In this paper, the authors evaluated the effect of fructooligosaccharides (FOS), xylooligosa-coarse (XOS) and a mixture of an antioxidant vitamin blend (AOB) on gut microbiota composition and activity, and intestinal barrier in vitro.
Abstract: Human gut microbiota (HGM) play a significant role in health and disease. Dietary components, including fiber, fat, proteins and micronutrients, can modulate HGM. Much research has been performed on conventional prebiotics such as fructooligosaccharides (FOS) and galactooligosaccharides (GOS), however, novel prebiotics or micronutrients still require further validation. We assessed the effect of FOS, xylooligosaccharides (XOS) and a mixture of an antioxidant vitamin blend (AOB) on gut microbiota composition and activity, and intestinal barrier in vitro. We used batch fermentations and tested the short-term effect of different products on microbial activity in six donors. Next, fecal inocula from two donors were used to inoculate the simulator of the human microbial ecosystem (SHIME) and after long-term exposure of FOS, XOS and AOB, microbial activity (short- and branched-chain fatty acids and lactate) and HGM composition were evaluated. Finally, in vitro assessment of intestinal barrier was performed in a Transwell setup of differentiated Caco-2 and HT29-MTX-E12 cells exposed to fermentation supernatants. Despite some donor-dependent differences, all three tested products showed beneficial modulatory effects on microbial activity represented by an increase in lactate and SCFA levels (acetate, butyrate and to a lesser extent also propionate), while decreasing proteolytic markers. Bifidogenic effect of XOS was consistent, while AOB supplementation appears to exert a specific impact on reducing F. nucleatum and increasing butyrate-producing B. wexlerae. Functional and compositional microbial changes were translated to an in vitro host response by increases of the intestinal barrier integrity by all the products and a decrease of the redox potential by AOB supplementation.

Journal ArticleDOI
Boris A. Gutman1, Theo G.M. van Erp2, Kathryn I. Alpert3, Christopher R.K. Ching4, Dmitry Isaev5, Anjani Ragothaman6, Neda Jahanshad4, Arvin Saremi4, Artemis Zavaliangos-Petropulu4, David C. Glahn7, Li Shen8, Shan Cong8, Dag Alnæs9, Ole A. Andreassen9, Nhat Trung Doan9, Lars T. Westlye9, Lars T. Westlye10, Peter Kochunov11, Theodore D. Satterthwaite8, Daniel H. Wolf8, Alexander J. Huang2, Charles Kessler2, Andrea Weideman2, Dana Nguyen2, Bryon A. Mueller12, Lawrence Faziola2, Steven G. Potkin2, Adrian Preda2, Daniel H. Mathalon13, Daniel H. Mathalon14, Juan R. Bustillo15, Vince D. Calhoun15, Vince D. Calhoun16, Judith M. Ford14, Judith M. Ford13, Esther Walton17, Stefan Ehrlich18, Giuseppe Ducci19, Nerisa Banaj, Fabrizio Piras, Federica Piras, Gianfranco Spalletta20, Erick J. Canales-Rodríguez, Paola Fuentes-Claramonte, Edith Pomarol-Clotet, Joaquim Radua, Raymond Salvador, Salvador Sarró, Erin W. Dickie21, Aristotle N. Voineskos21, Diana Tordesillas-Gutiérrez, Benedicto Crespo-Facorro22, Esther Setién-Suero, Jacqueline Mayoral-van Son22, Stefan Borgwardt23, Stefan Borgwardt24, Fabienne Schönborn-Harrisberger23, Derek W. Morris25, Gary Donohoe25, Laurena Holleran25, Dara M. Cannon25, Colm McDonald25, Aiden Corvin26, Michael Gill26, Geraldo Busatto Filho27, Pedro G.P. Rosa27, Mauricio H. Serpa27, Marcus V. Zanetti27, Irina V. Lebedeva, Kaleda Vg, Alexander Tomyshev, Timothy J. Crow28, Anthony A. James28, Simon Cervenka29, Carl M. Sellgren29, Helena Fatouros-Bergman29, Ingrid Agartz9, Fleur M. Howells30, Dan J. Stein30, Henk Temmingh30, Anne Uhlmann30, Anne Uhlmann18, Greig I. de Zubicaray31, Katie L. McMahon31, Margie Wright32, Derin Cobia33, Derin Cobia3, John G. Csernansky3, Paul M. Thompson4, Jessica A. Turner34, Lei Wang35, Lei Wang3 
TL;DR: In this paper, the authors employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants.
Abstract: Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1-weighted structural MRI scans. Mass univariate meta-analyses revealed more-concave-than-convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more-convex-than-concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta-analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.

Journal ArticleDOI
TL;DR: It is suggested that future research and development of alternative strategies to antibiotics and medicinal ZnO should pay attention to the role of vitamins for GI functionality and health of pigs.

Journal ArticleDOI
TL;DR: Dietary supplementation with benzoic acid positively modulated intestinal health by improving intestinal morphology and enriching microbial composition and significantly improved egg quality.

Journal ArticleDOI
TL;DR: In this article, a nuclease-defective mutant of Cas9 (dCas9) was fused to a highly active tripartite activator VP64-p65-Rta (VPR) to allow for sgRNA directed targeted gene regulation.
Abstract: Filamentous fungi are historically known to be a rich reservoir of bioactive compounds that are applied in a myriad of fields ranging from crop protection to medicine. The surge of genomic data available shows that fungi remain an excellent source for new pharmaceuticals. However, most of the responsible biosynthetic gene clusters are transcriptionally silent under laboratory growth conditions. Therefore, generic strategies for activation of these clusters are required. Here, we present a genome-editing-free, transcriptional regulation tool for filamentous fungi, based on the CRISPR activation (CRISPRa) methodology. Herein, a nuclease-defective mutant of Cas9 (dCas9) was fused to a highly active tripartite activator VP64-p65-Rta (VPR) to allow for sgRNA directed targeted gene regulation. dCas9-VPR was introduced, together with an easy to use sgRNA "plug-and-play" module, into a non-integrative AMA1-vector, which is compatible with several filamentous fungal species. To demonstrate its potential, this vector was used to transcriptionally activate a fluorescent reporter gene under the control of the penDE core promoter in Penicillium rubens. Subsequently, we activated the transcriptionally silent, native P. rubens macrophorin biosynthetic gene cluster by targeting dCas9-VPR to the promoter region of the transcription factor macR. This resulted in the production of antimicrobial macrophorins. This CRISPRa technology can be used for the rapid and convenient activation of silent fungal biosynthetic gene clusters, and thereby aid in the identification of novel compounds such as antimicrobials.

Journal ArticleDOI
05 Jan 2021
TL;DR: In this article, the authors found that the inclusion of sodium butyrate at moderate levels in a diet containing 0.5% benzoic acid improved growth performance of weaning pigs.
Abstract: Feed additives have been suggested to improve animal growth performance through modulating the gut microbiota. The hypothesis of this study was that the combination of two organic acids would exert synergistic effects on the growth performance and gut microbiota of weaning pigs. To test this hypothesis, we followed 398 weaning pigs from two university experiment stations (University of Illinois at Urbana-Champaign (UIUC) and University of Arkansas (UA)) to determine the effects of increasing levels (0%, 0.035%, 0.070%, and 0.105%) of sodium butyrate combined with 0.5% benzoic acid on the growth performance of nursery pigs. At the UA, an additional negative control diet was included and the gut microbiota analysis was carried out. At both universities, increasing levels of sodium butyrate in a diet containing 0.5% benzoic acid improved growth performance, which reached a plateau in the pigs fed 0.035% (SBA0.035) or 0.070% (SBA0.070) butyrate. Gut microbiota analysis revealed that pigs fed the SBA0.035 diet had more diverse microbiota and contained more potentially beneficial bacteria such as Oscillospira, Blautia, and Turicibacter and reduced levels of Veillonella and Sarcina. Results of the present study indicated that the inclusion of sodium butyrate at moderate levels in a diet containing 0.5% benzoic acid improved growth performance of weaning pigs and established potential health benefits on gut microbiota.

Journal ArticleDOI
TL;DR: Results showed that the picrocrocin and safranal content enables to differ dark-Dried samples from freeze-dried ones, and dark-drying can nullify the adverse effect of SaLV on crocins content.

Journal ArticleDOI
TL;DR: In this article, the aqueous solubility of the vinyl monomer was considered as a key parameter for overcoming this morphological limitation and a pseudo-phase diagram was constructed by systematically increasing the PHBMA target DP from 10 to 120 and varying the copolymer concentration between 5 and 20% w/w.

Journal ArticleDOI
04 May 2021
TL;DR: It is shown that there is a strong heterogeneity in the overall catalyst particle fragmentation and thus polymerization activity within the entire ensemble, which hints toward local mass transfer limitations or other deactivation phenomena.
Abstract: Ziegler-type catalysts are the grand old workhorse of the polyolefin industry, yet their hierarchically complex nature complicates polymerization activity-catalyst structure relationships. In this work, the degree of catalyst framework fragmentation of a high-density polyethylene (HDPE) Ziegler-type catalyst was studied using ptychography X-ray-computed nanotomography (PXCT) in the early stages of ethylene polymerization under mild reaction conditions. An ensemble consisting of 434 fully reconstructed ethylene prepolymerized Ziegler catalyst particles prepared at a polymer yield of 3.4 g HDPE/g catalyst was imaged. This enabled a statistical route to study the heterogeneity in the degree of particle fragmentation and therefore local polymerization activity at an achieved 3-D spatial resolution of 74 nm without requiring invasive imaging tools. To study the degree of catalyst fragmentation within the ensemble, a fragmentation parameter was constructed based on a k-means clustering algorithm that relates the quantity of polyethylene formed to the average size of the spatially resolved catalyst fragments. With this classification method, we have identified particles that exhibit weak, moderate, and strong degrees of catalyst fragmentation, showing that there is a strong heterogeneity in the overall catalyst particle fragmentation and thus polymerization activity within the entire ensemble. This hints toward local mass transfer limitations or other deactivation phenomena. The methodology used here can be applied to all polyolefin catalysts, including metallocene and the Phillips catalysts to gain statistically relevant fundamental insights in the fragmentation behavior of an ensemble of catalyst particles.

Journal ArticleDOI
TL;DR: Broadly, the results suggest inadequate vitamin E status in most age groups, with the prevalence of deficiency reaching 67%, 80%, 56% and 72% in infants, children and adolescents, adults, elderly and pregnant women, respectively, based on varying cut offs.
Abstract: Vitamin E is a lipid soluble antioxidant which mainly circulates as α-tocopherol in the human plasma. Its deficiency is associated with ataxia, neuropathy, anaemia and several other health conditions. Although substantial data on vitamin E status has been published worldwide, there is paucity of data on the extent of deficiency from most Asian countries, including India. Part of the problem is lack of validated biomarkers for vitamin E and no consensus on cut offs for defining deficiency and sufficiency. Thus, interpretation of the data on the vitamin E status is difficult. Limited available data from 31 studies on vitamin E status in healthy people from Asia, the most populated continent, has been collated for the purpose of this review. Broadly, the results suggest inadequate vitamin E status in most age groups, with the prevalence of deficiency reaching 67%, 80%, 56% and 72% in infants, children and adolescents, adults, elderly and pregnant women, respectively, based on varying cut offs. The findings are not surprising as both, vitamin E intakes and its status have not received too much attention in the past. Lack of conclusive data accentuates the need for more research on the vitamin E status across all age groups and to define age, gender and physiological state specific cut offs for vitamin E levels.

Journal ArticleDOI
TL;DR: In this paper, a model-based approach is advocated to optimize membrane bioreactors' performance, based on the type of membrane material, module, and flow configuration, to facilitate the enhancement of syngas fermentation rate.
Abstract: Syngas fermentation to biofuels and chemicals is an emerging technology in the biobased economy. Mass transfer is usually limiting the syngas fermentation rate, due to the low aqueous solubilities of the gaseous substrates. Membrane bioreactors, as efficient gas–liquid contactors, are a promising configuration for overcoming this gas-to-liquid mass transfer limitation, so that sufficient productivity can be achieved. We summarize the published performances of these reactors. Moreover, we highlight numerous parameters settings that need to be used for the enhancement of membrane bioreactor performance. To facilitate this enhancement, we relate mass transfer and other performance indicators to the type of membrane material, module, and flow configuration. Hollow fiber modules with dense or asymmetric membranes on which biofilm might form seem suitable. A model-based approach is advocated to optimize their performance.

Journal ArticleDOI
TL;DR: HAMR diet increased the abundance and activity of butyrate-producing bacteria and the concentration and absorption of SCFA, which may be associated with the decreased gene expression of inflammatory cytokines in the colonic mucosa of pigs with Prevotella-rich enterotype.