scholarly journals Prebiotics for Lactose Intolerance: Variability in Galacto-Oligosaccharide Utilization by Intestinal Lactobacillus rhamnosus

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1517 ◽  
Author(s):  
Jason Arnold ◽  
Joshua Simpson ◽  
Jeffery Roach ◽  
Jose Bruno-Barcena ◽  
M. Azcarate-Peril
Keyword(s):  
Lactose Intolerance ◽  
Critical Role ◽  
Lactobacillus Rhamnosus ◽  
Intestinal Bacteria ◽  
Bacterial Metabolism ◽  
Gastrointestinal Disorders ◽  
World Population ◽  
Carbohydrate Utilization ◽  
Putative Operon ◽  
Selection Of

Lactose intolerance, characterized by a decrease in host lactase expression, affects approximately 75% of the world population. Galacto-oligosaccharides (GOS) are prebiotics that have been shown to alleviate symptoms of lactose intolerance and to modulate the intestinal microbiota, promoting the growth of beneficial microorganisms. We hypothesized that mechanisms of GOS utilization by intestinal bacteria are variable, impacting efficacy and response, with differences occurring at the strain level. This study aimed to determine the mechanisms by which human-derived Lactobacillus rhamnosus strains metabolize GOS. Genomic comparisons between strains revealed differences in carbohydrate utilization components, including transporters, enzymes for degradation, and transcriptional regulation, despite a high overall sequence identity (>95%) between strains. Physiological and transcriptomics analyses showed distinct differences in carbohydrate metabolism profiles and GOS utilization between strains. A putative operon responsible for GOS utilization was identified and characterized by genetic disruption of the 6-phospho-β-galactosidase, which had a critical role in GOS utilization. Our findings highlight the importance of strain-specific bacterial metabolism in the selection of probiotics and synbiotics to alleviate symptoms of gastrointestinal disorders including lactose intolerance.

scholarly journals The Lamprey Forebrain – Evolutionary Implications

2021 ◽  
pp. 1-16
Author(s):  
Shreyas M. Suryanarayana ◽  
Juan Pérez-Fernández ◽  
Brita Robertson ◽  
Sten Grillner
Keyword(s):  
Basal Ganglia ◽  
Sensory Integration ◽  
Critical Role ◽  
Detailed Comparison ◽  
Common Ancestry ◽  
Dopamine System ◽  
Cortical Areas ◽  
Neural Processes ◽  
Living Group ◽  
Selection Of

The forebrain plays a critical role in a broad range of neural processes encompassing sensory integration and initiation/selection of behaviour. The forebrain functions through an interaction between different cortical areas, the thalamus, the basal ganglia with the dopamine system, and the habenulae. The ambition here is to compare the mammalian forebrain with that of the lamprey representing the oldest now living group of vertebrates, by a review of earlier studies. We show that the lamprey dorsal pallium has a motor, a somatosensory, and a visual area with retinotopic representation. The lamprey pallium was previously thought to be largely olfactory. There is also a detailed similarity between the lamprey and mammals with regard to other forebrain structures like the basal ganglia in which the general organisation, connectivity, transmitters and their receptors, neuropeptides, and expression of ion channels are virtually identical. These initially unexpected results allow for the possibility that many aspects of the basic design of the vertebrate forebrain had evolved before the lamprey diverged from the evolutionary line leading to mammals. Based on a detailed comparison between the mammalian forebrain and that of the lamprey and with due consideration of data from other vertebrate groups, we propose a compelling account of a pan-vertebrate schema for basic forebrain structures, suggesting a common ancestry of over half a billion years of vertebrate evolution.

scholarly journals Ocular growth and metabolomics are dependent upon the spectral content of ambient white light

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raymond P. Najjar ◽  
Juan Manuel Chao De La Barca ◽  
Veluchamy A. Barathi ◽  
Candice Ee Hua Ho ◽  
Jing Zhan Lock ◽  
...  
Keyword(s):  
Critical Role ◽  
Spectral Composition ◽  
Light Therapy ◽  
World Population ◽  
Spectral Content ◽  
Ocular Growth ◽  
Nitric Oxide Metabolism ◽  
Therapy Strategies ◽  
Indoor Lighting ◽  
The Impact

AbstractMyopia results from an excessive axial growth of the eye, causing abnormal projection of remote images in front of the retina. Without adequate interventions, myopia is forecasted to affect 50% of the world population by 2050. Exposure to outdoor light plays a critical role in preventing myopia in children, possibly through the brightness and blue-shifted spectral composition of sunlight, which lacks in artificial indoor lighting. Here, we evaluated the impact of moderate levels of ambient standard white (SW: 233.1 lux, 3900 K) and blue-enriched white (BEW: 223.8 lux, 9700 K) lights on ocular growth and metabolomics in a chicken-model of form-deprivation myopia. Compared to SW light, BEW light decreased aberrant ocular axial elongation and accelerated recovery from form-deprivation. Furthermore, the metabolomic profiles in the vitreous and retinas of recovering form-deprived eyes were distinct from control eyes and were dependent on the spectral content of ambient light. For instance, exposure to BEW light was associated with deep lipid remodeling and metabolic changes related to energy production, cell proliferation, collagen turnover and nitric oxide metabolism. This study provides new insight on light-dependent modulations in ocular growth and metabolomics. If replicable in humans, our findings open new potential avenues for spectrally-tailored light-therapy strategies for myopia.

scholarly journals Inhibitory Effects of Breast Milk-Derived Lactobacillus rhamnosus Probio-M9 on Colitis-Associated Carcinogenesis by Restoration of the Gut Microbiota in a Mouse Model

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1143
Author(s):  
Haiyan Xu ◽  
Keizo Hiraishi ◽  
Lin-Hai Kurahara ◽  
Yuko Nakano-Narusawa ◽  
Xiaodong Li ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Lactobacillus Rhamnosus ◽  
Tumor Model ◽  
Intestinal Bacteria ◽  
Inflammatory Cells ◽  
Shannon Index ◽  
Tumor Formation ◽  
Intestinal Bacterium ◽  
Α Diversity ◽  
Inflammatory Bowel

Chronic inflammation is a risk factor for colorectal cancer, and inflammatory cytokines secreted from inflammatory cells and active oxygen facilitate tumorigenesis. Intestinal bacteria are thought to regulate tumorigenesis. The longer the breastfeeding period, the lower is the risk of inflammatory bowel disease. Here, we investigated preventive effects of the probiotic Lactobacillus rhamnosus M9 (Probio-M9) on colitis-associated tumorigenesis. An inflammatory colorectal tumor model was established using a 6-week-old male C57BL/6NCrSlc mouse, which was intraperitoneally administered with azoxymethane (AOM: 12 mg/kg body weight). On weeks 2 and 4, 2% dextran sulfate sodium (DSS) was administered to mice for 7 days through drinking water. On weeks 8 and 10, Probio-M9 (2 × 109/day) was orally administered for 7 days. Animals were sacrificed at 20 weeks after AOM administration and immunohistochemical staining and Western blotting was performed. The α-diversity of microflora (Shannon index), principal coordinate analysis, and distribution of intestinal bacterium genera and metabolic pathways were compared. The AOM/DSS group showed weight loss, diarrhea, intestinal shortening, increased number of colon tumors, proliferating tumorigenesis, increased inflammation score, fibrosis, increased CD68+, or CD163+ macrophage cells in the subserosal layer of non-tumor areas. Inflammation and tumorigenesis ameliorated after Probio-M9 treatment. Fecal microbial functions were altered by AOM/DSS treatment. Probio-M9 significantly upregulated the fecal microbial diversity and reversed fecal microbial functions. Thus, Probio-M9 could suppress tumor formation in the large intestine by regulating the intestinal environment and ameliorating inflammation, suggesting its therapeutic potential for treatment of inflammation and colitis-associated tumorigenesis.

scholarly journals A New Hyper-Parameter Optimization Method for Power Load Forecast Based on Recurrent Neural Networks

Algorithms ◽  
2021 ◽  
Vol 14 (6) ◽  
pp. 163
Author(s):  
Yaru Li ◽  
Yulai Zhang ◽  
Yongping Cai
Keyword(s):  
Neural Networks ◽  
Parameter Optimization ◽  
Recurrent Neural Networks ◽  
Critical Role ◽  
Optimization Method ◽  
Bayesian Optimization ◽  
Power Load ◽  
Gradient Calculation ◽  
Truncated Newton ◽  
Selection Of

The selection of the hyper-parameters plays a critical role in the task of prediction based on the recurrent neural networks (RNN). Traditionally, the hyper-parameters of the machine learning models are selected by simulations as well as human experiences. In recent years, multiple algorithms based on Bayesian optimization (BO) are developed to determine the optimal values of the hyper-parameters. In most of these methods, gradients are required to be calculated. In this work, the particle swarm optimization (PSO) is used under the BO framework to develop a new method for hyper-parameter optimization. The proposed algorithm (BO-PSO) is free of gradient calculation and the particles can be optimized in parallel naturally. So the computational complexity can be effectively reduced which means better hyper-parameters can be obtained under the same amount of calculation. Experiments are done on real world power load data,where the proposed method outperforms the existing state-of-the-art algorithms,BO with limit-BFGS-bound (BO-L-BFGS-B) and BO with truncated-newton (BO-TNC),in terms of the prediction accuracy. The errors of the prediction result in different models show that BO-PSO is an effective hyper-parameter optimization method.

scholarly journals Untangling the environmental from the dietary: dust does not matter

2016 ◽  
Vol 283 (1838) ◽  
pp. 20161032 ◽  
Author(s):  
Gildas Merceron ◽  
Anusha Ramdarshan ◽  
Cécile Blondel ◽  
Jean-Renaud Boisserie ◽  
Noël Brunetiere ◽  
...  
Keyword(s):  
Critical Role ◽  
Tooth Wear ◽  
Textural Analysis ◽  
Significant Determinant ◽  
Intrinsic Properties ◽  
Dental Microwear ◽  
Natural Conditions ◽  
Evolutionary Mechanisms ◽  
Food Items ◽  
Selection Of

Both dust and silica phytoliths have been shown to contribute to reducing tooth volume during chewing. However, the way and the extent to which they individually contribute to tooth wear in natural conditions is unknown. There is still debate as to whether dental microwear represents a dietary or an environmental signal, with far-reaching implications on evolutionary mechanisms that promote dental phenotypes, such as molar hypsodonty in ruminants, molar lengthening in suids or enamel thickening in human ancestors. By combining controlled-food trials simulating natural conditions and dental microwear textural analysis on sheep, we show that the presence of dust on food items does not overwhelm the dietary signal. Our dataset explores variations in dental microwear textures between ewes fed on dust-free and dust-laden grass or browse fodders. Browsing diets with a dust supplement simulating Harmattan windswept environments contain more silica than dust-free grazing diets. Yet browsers given a dust supplement differ from dust-free grazers. Regardless of the presence or the absence of dust, sheep with different diets yield significantly different dental microwear textures. Dust appears a less significant determinant of dental microwear signatures than the intrinsic properties of ingested foods, implying that diet plays a critical role in driving the natural selection of dental innovations.

scholarly journals Standards of Proof and Civil Litigation: A Game-Theoretic Analysis

2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Alice Guerra ◽  
Barbara Luppi ◽  
Francesco Parisi
Keyword(s):  
Critical Role ◽  
Policy Instrument ◽  
Civil Litigation ◽  
Access To Justice ◽  
Standard Of Proof ◽  
Game Theoretic Analysis ◽  
Standards Of Proof ◽  
Game Theoretic ◽  
Truth Finding ◽  
Selection Of

AbstractIn litigation models, the parties’ probability to succeed in a lawsuit hinge upon the merits of the parties’ claims and their litigation efforts. In this paper we extend this framework to consider an important procedural aspect of the legal system: the standard of proof. We recast the conventional litigation model to consider how alternative standards of proof affect litigation choices. We analyze the interrelation between different standards of proof, the effectiveness of the parties’ efforts, and the merits of the case. We study how these factors jointly affect the parties’ litigation expenditures, the selection of cases brought to the courts, pretrial bargain solutions and preemptive strategies. Our results show that standards of proof are not only instrumental to balancing the competing goals of access to justice and judicial truth-finding, but they also play a critical role in affecting parties’ litigation investments and settlement choices, and in sorting the mix of cases that will actually be filed and defended in courts. The understanding of the sorting effect of standards of proof sheds light on their role as a policy instrument in civil litigation.

scholarly journals Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Mariia Novikova ◽  
Lucas J. Adams ◽  
Juan Fontana ◽  
Anna T. Gres ◽  
Muthukumar Balasubramaniam ◽  
...  
Keyword(s):  
Virus Assembly ◽  
Critical Role ◽  
Replication Cycle ◽  
Structural Defects ◽  
Fold Axis ◽  
Structural Element ◽  
Particle Assembly ◽  
Compensatory Mutations ◽  
Hiv 1 ◽  
Selection Of

ABSTRACTLate in the HIV-1 replication cycle, the viral structural protein Gag is targeted to virus assembly sites at the plasma membrane of infected cells. The capsid (CA) domain of Gag plays a critical role in the formation of the hexameric Gag lattice in the immature virion, and, during particle release, CA is cleaved from the Gag precursor by the viral protease and forms the conical core of the mature virion. A highly conserved Pro-Pro-Ile-Pro (PPIP) motif (CA residues 122 to 125) [PPIP(122–125)] in a loop connecting CA helices 6 and 7 resides at a 3-fold axis formed by neighboring hexamers in the immature Gag lattice. In this study, we characterized the role of this PPIP(122–125) loop in HIV-1 assembly and maturation. While mutations P123A and P125A were relatively well tolerated, mutation of P122 and I124 significantly impaired virus release, caused Gag processing defects, and abolished infectivity. X-ray crystallography indicated that the P122A and I124A mutations induce subtle changes in the structure of the mature CA lattice which were permissive forin vitroassembly of CA tubes. Transmission electron microscopy and cryo-electron tomography demonstrated that the P122A and I124A mutations induce severe structural defects in the immature Gag lattice and abrogate conical core formation. Propagation of the P122A and I124A mutants in T-cell lines led to the selection of compensatory mutations within CA. Our findings demonstrate that the CA PPIP(122–125) loop comprises a structural element critical for the formation of the immature Gag lattice.IMPORTANCECapsid (CA) plays multiple roles in the HIV-1 replication cycle. CA-CA domain interactions are responsible for multimerization of the Gag polyprotein at virus assembly sites, and in the mature virion, CA monomers assemble into a conical core that encapsidates the viral RNA genome. Multiple CA regions that contribute to the assembly and release of HIV-1 particles have been mapped and investigated. Here, we identified and characterized a Pro-rich loop in CA that is important for the formation of the immature Gag lattice. Changes in this region disrupt viral production and abrogate the formation of infectious, mature virions. Propagation of the mutants in culture led to the selection of second-site compensatory mutations within CA. These results expand our knowledge of the assembly and maturation steps in the viral replication cycle and may be relevant for development of antiviral drugs targeting CA.

scholarly journals Investigating the role of noncoding regulatory DNA in plasmid development for Yarrowia lipolytica

2020 ◽  
Author(s):  
Carmen Lopez ◽  
Mingfeng Cao ◽  
Zhanyi Yao ◽  
Zengyi Shao
Keyword(s):  
Yarrowia Lipolytica ◽  
Plasmid Stability ◽  
Critical Role ◽  
Fold Increase ◽  
Microbial Cell Factories ◽  
Cell Factories ◽  
Expression Platform ◽  
Regulatory Dna ◽  
Selection Of

Production of industrially relevant compounds in microbial cell factories can employ either genomes or plasmids as an expression platform. Selection of plasmids as pathway carriers is advantageous for rapid demonstration but poses a challenge of stability. Yarrowia lipolytica has attracted great attention in the past decade for the biosynthesis of chemicals related to fatty acids at titers attractive to industry, and many genetic tools have been developed to explore its oleaginous potential. Our recent studies on the autonomously replicating sequences (ARSs) of nonconventional yeasts revealed that the ARSs from Y. lipolytica showcase a unique structure that includes a previously unannotated sequence (spacer) linking the origin of replication (ORI) and the centromeric (CEN) element and plays a critical role in modulating plasmid behavior. Maintaining a native 645-bp spacer yielded a 4.5-fold increase in gene expression and higher plasmid stability compared to a more universally employed minimized ARS. Testing the modularity of the ARS sub-elements indicated that plasmid stability exhibits a pronounced cargo dependency. Instability caused both plasmid loss and intramolecular rearrangements. Altogether, our work clarifies the appropriate application of various ARSs for the scientific community and sheds light on a previously unexplored DNA element as a potential target for engineering Y. lipolytica.

scholarly journals Positively Correlated CD47 Activation and Autophagy in Umbilical Cord Blood-Derived Mesenchymal Stem Cells during Senescence

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Gee-Hye Kim ◽  
Yun Kyung Bae ◽  
Ji Hye Kwon ◽  
Miyeon Kim ◽  
Soo Jin Choi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Growth ◽  
Cell Therapy ◽  
Critical Role ◽  
Therapeutic Effects ◽  
Stem Cell Maintenance ◽  
Selection Of

Autophagy plays a critical role in stem cell maintenance and is related to cell growth and cellular senescence. It is important to find a quality-control marker for predicting senescent cells. This study verified that CD47 could be a candidate to select efficient mesenchymal stem cells (MSCs) to enhance the therapeutic effects of stem cell therapy by analyzing the antibody surface array. CD47 expression was significantly decreased during the expansion of MSCs in vitro ( p < 0.01 ), with decreased CD47 expression correlated with accelerated senescence phenotype, which affected cell growth. UCB-MSCs transfected with CD47 siRNA significantly triggered the downregulation of pRB and upregulation of pp38, which are senescence-related markers. Additionally, autophagy-related markers, ATG5, ATG12, Beclin1, and LC3B, revealed significant downregulation with CD47 siRNA transfection. Furthermore, autophagy flux following treatment with an autophagy inducer, rapamycin, has shown that CD47 is a key player in autophagy and senescence to maintain and regulate the growth of MSCs, suggesting that CD47 may be a critical key marker for the selection of effective stem cells in cell therapy.

scholarly journals Genomics Armed With Diversity Leads the Way in Brassica Improvement in a Changing Global Environment

2021 ◽  
Vol 12 ◽  
Author(s):  
Nur Shuhadah Mohd Saad ◽  
Anita A. Severn-Ellis ◽  
Aneeta Pradhan ◽  
David Edwards ◽  
Jacqueline Batley
Keyword(s):  
Climate Change ◽  
Reverse Genetics ◽  
Agronomic Traits ◽  
Crop Evolution ◽  
Breeding Cycle ◽  
World Population ◽  
Genome Wide ◽  
The Face ◽  
Selection Of ◽  
The Way

Meeting the needs of a growing world population in the face of imminent climate change is a challenge; breeding of vegetable and oilseed Brassica crops is part of the race in meeting these demands. Available genetic diversity constituting the foundation of breeding is essential in plant improvement. Elite varieties, land races, and crop wild species are important resources of useful variation and are available from existing genepools or genebanks. Conservation of diversity in genepools, genebanks, and even the wild is crucial in preventing the loss of variation for future breeding efforts. In addition, the identification of suitable parental lines and alleles is critical in ensuring the development of resilient Brassica crops. During the past two decades, an increasing number of high-quality nuclear and organellar Brassica genomes have been assembled. Whole-genome re-sequencing and the development of pan-genomes are overcoming the limitations of the single reference genome and provide the basis for further exploration. Genomic and complementary omic tools such as microarrays, transcriptomics, epigenetics, and reverse genetics facilitate the study of crop evolution, breeding histories, and the discovery of loci associated with highly sought-after agronomic traits. Furthermore, in genomic selection, predicted breeding values based on phenotype and genome-wide marker scores allow the preselection of promising genotypes, enhancing genetic gains and substantially quickening the breeding cycle. It is clear that genomics, armed with diversity, is set to lead the way in Brassica improvement; however, a multidisciplinary plant breeding approach that includes phenotype = genotype × environment × management interaction will ultimately ensure the selection of resilient Brassica varieties ready for climate change.

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