scholarly journals Structure and evolution of the bifidobacterial carbohydrate metabolism proteins and enzymes

2021 ◽  
Author(s):  
Shinya Fushinobu ◽  
Maher Abou Hachem
Keyword(s):  
Abc Transporters ◽  
Bifidobacterium Longum ◽  
Three Dimensional ◽  
Bifidobacterium Bifidum ◽  
Structural Basis ◽  
Structural Elements ◽  
Competitive Growth ◽  
Symbiotic Relationships ◽  
History Of ◽  
Health Promoting

Bifidobacteria have attracted significant attention because they provide health-promoting effects in the human gut. In this review, we present a current overview of the three-dimensional structures of bifidobacterial proteins involved in carbohydrate uptake, degradation, and metabolism. As predominant early colonizers of the infant's gut, distinct bifidobacterial species are equipped with a panel of transporters and enzymes specific for human milk oligosaccharides (HMOs). Interestingly, Bifidobacterium bifidum and Bifidobacterium longum possess lacto-N-biosidases with unrelated structural folds to release the disaccharide lacto-N-biose from HMOs, suggesting the convergent evolution of this activity from different ancestral proteins. The crystal structures of enzymes that confer the degradation of glycans from the mucin glycoprotein layer provide a structural basis for the utilization of this sustainable nutrient in the gastrointestinal tract. The utilization of several plant dietary oligosaccharides has been studied in detail, and the prime importance of oligosaccharide-specific ATP-binding cassette (ABC) transporters in glycan utilisations by bifidobacteria has been revealed. The structural elements underpinning the high selectivity and roles of ABC transporter binding proteins in establishing competitive growth on preferred oligosaccharides are discussed. Distinct ABC transporters are conserved across several bifidobacterial species, e.g. those targeting arabinoxylooligosaccharide and α-1,6-galactosides/glucosides. Less prevalent transporters, e.g. targeting β-mannooligosaccharides, may contribute to the metabolic specialisation within Bifidobacterium. Some bifidobacterial species have established symbiotic relationships with humans. Structural studies of carbohydrate-utilizing systems in Bifidobacterium have revealed the interesting history of molecular coevolution with the host, as highlighted by the early selection of bifidobacteria by mucin and breast milk glycans.

Designing TIMP (tissue inhibitor of metalloproteinases) variants that are selective metalloproteinase inhibitors

2003 ◽  
Vol 70 ◽  
pp. 201-212 ◽  
Author(s):  
Hideaki Nagase ◽  
Keith Brew
Keyword(s):  
Three Dimensional ◽  
Therapeutic Interventions ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Structural Basis ◽  
Structural Elements ◽  
Ridge Structure ◽  
Extracellular Matrix Components ◽  
Metalloproteinase Inhibitors ◽  
The Matrix ◽  
A Disintegrin And Metalloproteinase

The tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of the matrix metalloproteinases (MMPs), enzymes that play central roles in the degradation of extracellular matrix components. The balance between MMPs and TIMPs is important in the maintenance of tissues, and its disruption affects tissue homoeostasis. Four related TIMPs (TIMP-1 to TIMP-4) can each form a complex with MMPs in a 1:1 stoichiometry with high affinity, but their inhibitory activities towards different MMPs are not particularly selective. The three-dimensional structures of TIMP-MMP complexes reveal that TIMPs have an extended ridge structure that slots into the active site of MMPs. Mutation of three separate residues in the ridge, at positions 2, 4 and 68 in the amino acid sequence of the N-terminal inhibitory domain of TIMP-1 (N-TIMP-1), separately and in combination has produced N-TIMP-1 variants with higher binding affinity and specificity for individual MMPs. TIMP-3 is unique in that it inhibits not only MMPs, but also several ADAM (a disintegrin and metalloproteinase) and ADAMTS (ADAM with thrombospondin motifs) metalloproteinases. Inhibition of the latter groups of metalloproteinases, as exemplified with ADAMTS-4 (aggrecanase 1), requires additional structural elements in TIMP-3 that have not yet been identified. Knowledge of the structural basis of the inhibitory action of TIMPs will facilitate the design of selective TIMP variants for investigating the biological roles of specific MMPs and for developing therapeutic interventions for MMP-associated diseases.

scholarly journals Exploring the Diversity of the Bifidobacterial Population in the Human Intestinal Tract

2009 ◽  
Vol 75 (6) ◽  
pp. 1534-1545 ◽  
Author(s):  
Francesca Turroni ◽  
Elena Foroni ◽  
Paola Pizzetti ◽  
Vanessa Giubellini ◽  
Angela Ribbera ◽  
...  
Keyword(s):  
Bifidobacterium Longum ◽  
Bifidobacterium Bifidum ◽  
Selective Medium ◽  
Rrna Gene ◽  
Bifidobacterium Adolescentis ◽  
Fecal Samples ◽  
Bifidobacterium Animalis ◽  
Human Intestinal Microbiota ◽  
Health Promoting ◽  
Internally Transcribed Spacer

ABSTRACT Although the health-promoting roles of bifidobacteria are widely accepted, the diversity of bifidobacteria among the human intestinal microbiota is still poorly understood. We performed a census of bifidobacterial populations from human intestinal mucosal and fecal samples by plating them on selective medium, coupled with molecular analysis of selected rRNA gene sequences (16S rRNA gene and internally transcribed spacer [ITS] 16S-23S spacer sequences) of isolated colonies. A total of 900 isolates were collected, of which 704 were shown to belong to bifidobacteria. Analyses showed that the culturable bifidobacterial population from intestinal and fecal samples include six main phylogenetic taxa, i.e., Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium pseudolongum, Bifidobacterium breve, and Bifidobacterium bifidum, and two species mostly detected in fecal samples, i.e., Bifidobacterium dentium and Bifidobacterium animalis subp. lactis. Analysis of bifidobacterial distribution based on age of the subject revealed that certain identified bifidobacterial species were exclusively present in the adult human gut microbiota whereas others were found to be widely distributed. We encountered significant intersubject variability and composition differences between fecal and mucosa-adherent bifidobacterial communities. In contrast, a modest diversification of bifidobacterial populations was noticed between different intestinal regions within the same individual (intrasubject variability). Notably, a small number of bifidobacterial isolates were shown to display a wide ecological distribution, thus suggesting that they possess a broad colonization capacity.

Electron Microscopy and image reconstruction reveal the structural basis for spectrin's elastic properties

1992 ◽  
Vol 50 (1) ◽  
pp. 510-511
Author(s):  
Amy M. McGough ◽  
Robert Josephs
Keyword(s):  
Electron Microscopy ◽  
Elastic Properties ◽  
Conformational Changes ◽  
Quaternary Structure ◽  
Three Dimensional ◽  
Membrane Skeleton ◽  
Projection Algorithm ◽  
Structural Basis ◽  
Iterative Approximation ◽  
Membrane Skeletons

The remarkable deformability of the erythrocyte derives in large part from the elastic properties of spectrin, the major component of the membrane skeleton. It is generally accepted that spectrin's elasticity arises from marked conformational changes which include variations in its overall length (1). In this work the structure of spectrin in partially expanded membrane skeletons was studied by electron microscopy to determine the molecular basis for spectrin's elastic properties. Spectrin molecules were analysed with respect to three features: length, conformation, and quaternary structure. The results of these studies lead to a model of how spectrin mediates the elastic deformation of the erythrocyte.Membrane skeletons were isolated from erythrocyte membrane ghosts, negatively stained, and examined by transmission electron microscopy (2). Particle lengths and end-to-end distances were measured from enlarged prints using the computer program MACMEASURE. Spectrin conformation (straightness) was assessed by calculating the particles’ correlation length by iterative approximation (3). Digitised spectrin images were correlation averaged or Fourier filtered to improve their signal-to-noise ratios. Three-dimensional reconstructions were performed using a suite of programs which were based on the filtered back-projection algorithm and executed on a cluster of Microvax 3200 workstations (4).

Sea Urchins and Circuses: The Modernist Natural Histories of Jean Painlevé and Alexander Calder

2018 ◽  
Vol 13 (2) ◽  
pp. 187-211
Author(s):  
Patricia E. Chu
Keyword(s):  
New Media ◽  
Sea Urchins ◽  
Life Sciences ◽  
Three Dimensional ◽  
Machine Age ◽  
Avant Garde ◽  
History Of ◽  
And Performance ◽  
The One ◽  
Natural Historian

The Paris avant-garde milieu from which both Cirque Calder/Calder's Circus and Painlevé’s early films emerged was a cultural intersection of art and the twentieth-century life sciences. In turning to the style of current scientific journals, the Paris surrealists can be understood as engaging the (life) sciences not simply as a provider of normative categories of materiality to be dismissed, but as a companion in apprehending the “reality” of a world beneath the surface just as real as the one visible to the naked eye. I will focus in this essay on two modernist practices in new media in the context of the history of the life sciences: Jean Painlevé’s (1902–1989) science films and Alexander Calder's (1898–1976) work in three-dimensional moving art and performance—the Circus. In analyzing Painlevé’s work, I discuss it as exemplary of a moment when life sciences and avant-garde technical methods and philosophies created each other rather than being classified as separate categories of epistemological work. In moving from Painlevé’s films to Alexander Calder's Circus, Painlevé’s cinematography remains at the forefront; I use his film of one of Calder's performances of the Circus, a collaboration the men had taken two decades to complete. Painlevé’s depiction allows us to see the elements of Calder's work that mark it as akin to Painlevé’s own interest in a modern experimental organicism as central to the so-called machine-age. Calder's work can be understood as similarly developing an avant-garde practice along the line between the bestiary of the natural historian and the bestiary of the modern life scientist.

Galacto- and Fructo-oligosaccharides Utilized for Growth by Cocultures of Bifidobacterial Species Characteristic of the Infant Gut

2020 ◽  
Author(s):  
Ian Sims ◽  
GW Tannock
Keyword(s):  
Breast Milk ◽  
Bacterial Species ◽  
Bifidobacterium Longum ◽  
Well Being ◽  
Bifidobacterium Bifidum ◽  
Child Rearing ◽  
Potential Growth ◽  
Human Infants ◽  
Infant Diet ◽  
Growth Substrates

Copyright © 2020 American Society for Microbiology. Bifidobacterial species are common inhabitants of the gut of human infants during the period when milk is a major component of the diet. Bifidobacterium breve, Bifidobacterium bifidum, Bifidobacterium longum subspecies longum, and B. longum subspecies infantis have been detected frequently in infant feces, but B. longum subsp. infantis may be disadvantaged numerically in the gut of infants in westernized countries. This may be due to the different durations of breast milk feeding in different countries. Supplementation of the infant diet or replacement of breast milk using formula feeds is common in Western countries. Formula milks often contain galacto- and/or fructo-oligosaccharides (GOS and FOS, respectively) as additives to augment the concentration of oligosaccharides in ruminant milks, but the ability of B. longum subsp. infantis to utilize these potential growth substrates when they are in competition with other bifidobacterial species is unknown. We compared the growth and oligosaccharide utilization of GOS and FOS by bifidobacterial species in pure culture and coculture. Short-chain GOS and FOS (degrees of polymerization [DP] 2 and 3) were favored growth substrates for strains of B. bifidum and B. longum subsp. longum, whereas both B. breve and B. longum subsp. infantis had the ability to utilize both short- and longer-chain GOS and FOS (DP 2 to 6). B. breve was nevertheless numerically dominant over B. longum subsp. infantis in cocultures. This was probably related to the slower use of GOS of DP 3 by B. longum subsp. infantis, indicating that the kinetics of substrate utilization is an important ecological factor in the assemblage of gut communities.IMPORTANCE The kinds of bacteria that form the collection of microbes (the microbiota) in the gut of human infants may influence health and well-being. Knowledge of how the composition of the infant diet influences the assemblage of the bacterial collection is therefore important because dietary interventions may offer opportunities to alter the microbiota with the aim of improving health. Bifidobacterium longum subspecies infantis is a well-known bacterial species, but under modern child-rearing conditions it may be disadvantaged in the gut. Modern formula milks often contain particular oligosaccharide additives that are generally considered to support bifidobacterial growth. However, studies of the ability of various bifidobacterial species to grow together in the presence of these oligosaccharides have not been conducted. These kinds of studies are essential for developing concepts of microbial ecology related to the influence of human nutrition on the development of the gut microbiota.

Computed Tomography and Magnetic Resonance Imaging-aided Diagnosis of Primary Essential Cutis Verticis Gyrata: A Case Report with 5-year Follow-up and Review of the Literature

2019 ◽  
Vol 15 (9) ◽  
pp. 906-910
Author(s):  
Hongzhang Zhu ◽  
Shi-Ting Feng ◽  
Xingqi Zhang ◽  
Zunfu Ke ◽  
Ruixi Zeng ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Three Dimensional ◽  
Stable Condition ◽  
Resonance Imaging ◽  
Mri Findings ◽  
Cutis Verticis Gyrata ◽  
Essential Form ◽  
History Of ◽  
Magnetic Resonance Imaging Mri

Background: Cutis Verticis Gyrata (CVG) is a rare skin disease caused by overgrowth of the scalp, presenting as cerebriform folds and wrinkles. CVG can be classified into two forms: primary (essential and non-essential) and secondary. The primary non-essential form is often associated with neurological and ophthalmological abnormalities, while the primary essential form occurs without associated comorbidities. Discussion: We report on a rare case of primary essential CVG with a 4-year history of normal-colored scalp skin mass in the parietal-occipital region without symptom in a 34-year-old male patient, retrospectively summarizing his pathological and Computer Tomography (CT) and magnetic resonance imaging (MRI) findings. The major clinical observations on the CT and MR sectional images include a thickened dermis and excessive growth of the scalp, forming the characteristic scalp folds. With the help of CT and MRI Three-dimensional (3D) reconstruction techniques, the characteristic skin changes could be displayed intuitively, providing more evidence for a diagnosis of CVG. At the 5-year followup, there were no obvious changes in the lesion. Conclusion: Based on our observations, we propose that not all patients with primary essential CVG need surgical intervention, and continuous clinical observation should be an appropriate therapy for those in stable condition.

scholarly journals Rely on Each Other: DNA Binding Cooperativity Shapes p53 Functions in Tumor Suppression and Cancer Therapy

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2422
Author(s):  
Oleg Timofeev ◽  
Thorsten Stiewe
Keyword(s):  
Cancer Therapy ◽  
Dna Binding ◽  
Cell Fate ◽  
Tumor Suppression ◽  
Quaternary Structure ◽  
Three Dimensional ◽  
Structural Basis ◽  
Sequence Specificity ◽  
Cell Fate Decisions ◽  
Cancer Mutations

p53 is a tumor suppressor that is mutated in half of all cancers. The high clinical relevance has made p53 a model transcription factor for delineating general mechanisms of transcriptional regulation. p53 forms tetramers that bind DNA in a highly cooperative manner. The DNA binding cooperativity of p53 has been studied by structural and molecular biologists as well as clinical oncologists. These experiments have revealed the structural basis for cooperative DNA binding and its impact on sequence specificity and target gene spectrum. Cooperativity was found to be critical for the control of p53-mediated cell fate decisions and tumor suppression. Importantly, an estimated number of 34,000 cancer patients per year world-wide have mutations of the amino acids mediating cooperativity, and knock-in mouse models have confirmed such mutations to be tumorigenic. While p53 cancer mutations are classically subdivided into “contact” and “structural” mutations, “cooperativity” mutations form a mechanistically distinct third class that affect the quaternary structure but leave DNA contacting residues and the three-dimensional folding of the DNA-binding domain intact. In this review we discuss the concept of DNA binding cooperativity and highlight the unique nature of cooperativity mutations and their clinical implications for cancer therapy.

Gender Differences and Their Influences on T2DM Self-Management Among Spanish-Speaking Latinx Immigrants

2021 ◽  
pp. 154041532110117
Author(s):  
Cheryl A. Smith-Miller ◽  
Diane C. Berry ◽  
Cass T. Miller
Keyword(s):  
Gender Differences ◽  
Health Literacy ◽  
English Language ◽  
Educational Achievement ◽  
Self Management ◽  
Structured Interviews ◽  
Health Promoting Behaviors ◽  
History Of ◽  
Health Promoting ◽  
Excessive Alcohol

Introduction: Evidence suggests that gender may influence many aspects of type 2 diabetes (T2DM) self-management (SM) and we posit that limited English language–proficient Latinx immigrants face additional challenges. Methods: Instruments and semi-structured interviews were used to examine gender differences on health literacy, diabetes knowledge, health-promoting behaviors, diabetes, eating and exercise self-efficacy (SE), and T2DM SM practices among a cohort of limited English language–proficient Latinx immigrants. Statistical and qualitative analysis procedures were performed comparing males and females. Results: Thirty persons participated. Males tended to be older, have higher educational achievement, and more financial security than females. Physiologic measures tended worse among female participants. Health literacy and exercise SE scores were similar, but females scored lower on Eating and Diabetes SE. Forty-seven percent ( n= 9) of the women reported a history of gestational diabetes mellitus and a majority of men ( n = 7) cited difficulty with excessive alcohol. Consumption: Males appeared to receive more SM support compared to females. Females more frequently noted how family obligations and a lack of support impeded their SM. Work environments negatively influenced SM practices. Conclusion: Men and women have unique SM challenges and as such require individualized strategies and support to improve T2DM management.

scholarly journals Sirenomelia: two case reports

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Asiyeh Shojaee ◽  
Firooze Ronnasian ◽  
Mahdiyeh Behnam ◽  
Mansoor Salehi
Keyword(s):  
Case Reports ◽  
Three Dimensional ◽  
First Trimester ◽  
Mendelian Inheritance ◽  
Lower Limbs ◽  
Congenital Deformity ◽  
White Family ◽  
Her Family ◽  
Caudal Regression ◽  
History Of

AbstractBackgroundSirenomelia, also called mermaid syndrome, is a rare lethal multi-system congenital deformity with an incidence of one in 60,000–70,000 pregnancies. Sirenomelia is mainly characterized by the fusion of lower limbs and is widely associated with severe urogenital and gastrointestinal malformations. The presence of a single umbilical artery derived from the vitelline artery is the main anatomical feature distinguishing sirenomelia from caudal regression syndrome. First-trimester diagnosis of this disorder and induced abortion may be the safest medical option. In this report, two cases of sirenomelia that occurred in an white family will be discussed.Case presentationWe report two white cases of sirenomelia occurring in a 31-year-old multigravid pregnant woman. In the first pregnancy (18 weeks of gestation) abortion was performed, but in the third pregnancy (32 weeks) the stillborn baby was delivered by spontaneous vaginal birth. In the second and fourth pregnancies, however, she gave birth to normal babies. Three-dimensional ultrasound imaging showed fusion of the lower limbs. Neither she nor any member of her family had a history of diabetes. In terms of other risk factors, she had no history of exposure to teratogenic agents during her pregnancy. Also, her marriage was non-consanguineous.ConclusionThis report suggests the existence of a genetic background in this mother with a Mendelian inheritance pattern of 50% second-generation incidence in her offspring.

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