scholarly journals ADAMTS9 and ADAMTS20 are differentially affected by loss of B3GLCT in mouse model of Peters plus syndrome

2019 ◽  
Vol 28 (24) ◽  
pp. 4053-4066 ◽  
Author(s):  
Bernadette C Holdener ◽  
Christopher J Percival ◽  
Richard C Grady ◽  
Daniel C Cameron ◽  
Steven J Berardinelli ◽  
...  
Keyword(s):  
Compelling Evidence ◽  
Partial Reduction ◽  
Mouse Development ◽  
Developmental Defects ◽  
Highly Sensitive ◽  
Modified Proteins ◽  
Thrombospondin Type 1 Repeats ◽  
Insight Into

Abstract Peters plus syndrome (MIM #261540 PTRPLS), characterized by defects in eye development, prominent forehead, hypertelorism, short stature and brachydactyly, is caused by mutations in the β3-glucosyltransferase (B3GLCT) gene. Protein O-fucosyltransferase 2 (POFUT2) and B3GLCT work sequentially to add an O-linked glucose β1-3fucose disaccharide to properly folded thrombospondin type 1 repeats (TSRs). Forty-nine proteins are predicted to be modified by POFUT2, and nearly half are members of the ADAMTS superfamily. Previous studies suggested that O-linked fucose is essential for folding and secretion of POFUT2-modified proteins and that B3GLCT-mediated extension to the disaccharide is essential for only a subset of targets. To test this hypothesis and gain insight into the origin of PTRPLS developmental defects, we developed and characterized two mouse B3glct knockout alleles. Using these models, we tested the role of B3GLCT in enabling function of ADAMTS9 and ADAMTS20, two highly conserved targets whose functions are well characterized in mouse development. The mouse B3glct mutants developed craniofacial and skeletal abnormalities comparable to PTRPLS. In addition, we observed highly penetrant hydrocephalus, white spotting and soft tissue syndactyly. We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function. Combined, these results provide compelling evidence that ADAMTS9 and ADAMTS20 were differentially sensitive to B3GLCT inactivation and suggest that the developmental defects in PTRPLS result from disruption of a subset of highly sensitive POFUT2/B3GLCT targets such as ADAMTS20.

scholarly journals The Role of the Fibronectin IGD Motif in Stimulating Fibroblast Migration

2007 ◽  
Vol 282 (49) ◽  
pp. 35530-35535 ◽  
Author(s):  
Christopher J. Millard ◽  
Ian R. Ellis ◽  
Andrew R. Pickford ◽  
Ana M. Schor ◽  
Seth L. Schor ◽  
...  
Keyword(s):  
Fibroblast Migration ◽  
Wide Range ◽  
Migration Stimulating Factor ◽  
Function Relationship ◽  
Relationship Of ◽  
Stimulating Factor ◽  
Insight Into ◽  
Stimulation Of

The motogenic activity of migration-stimulating factor, a truncated isoform of fibronectin (FN), has been attributed to the IGD motifs present in its FN type 1 modules. The structure-function relationship of various recombinant IGD-containing FN fragments is now investigated. Their structure is assessed by solution state NMR and their motogenic ability tested on fibroblasts. Even conservative mutations in the IGD motif are inactive or have severely reduced potency, while the structure remains essentially the same. A fragment with two IGD motifs is 100 times more active than a fragment with one and up to 106 times more than synthetic tetrapeptides. The wide range of potency in different contexts is discussed in terms of cryptic FN sites and cooperativity. These results give new insight into the stimulation of fibroblast migration by IGD motifs in FN.

A key role for IL-13 signaling via the type 2 IL-4 receptor in experimental atopic dermatitis

2020 ◽  
Vol 5 (44) ◽  
pp. eaaw2938 ◽  
Author(s):  
Almog Bitton ◽  
Shmuel Avlas ◽  
Hadar Reichman ◽  
Michal Itan ◽  
Danielle Karo-Atar ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Allergic Diseases ◽  
Proof Of Concept ◽  
Potential Therapeutic Target ◽  
Tnf Α ◽  
Allergic Skin ◽  
Insight Into

IL-13 and IL-4 are potent mediators of type 2–associated inflammation such as those found in atopic dermatitis (AD). IL-4 shares overlapping biological functions with IL-13, a finding that is mainly explained by their ability to signal via the type 2 IL-4 receptor (R), which is composed of IL-4Rα in association with IL-13Rα1. Nonetheless, the role of the type 2 IL-4R in AD remains to be clearly defined. Induction of two distinct models of experimental AD in Il13ra1−/− mice, which lack the type 2 IL-4R, revealed that dermatitis, including ear and epidermal thickening, was dependent on type 2 IL-4R signaling. Expression of TNF-α was dependent on the type 2 IL-4R, whereas induction of IL-4, IgE, CCL24, and skin eosinophilia was dependent on the type 1 IL-4R. Neutralization of IL-4, IL-13, and TNF-α as well as studies in bone marrow–chimeric mice revealed that dermatitis, TNF-α, CXCL1, and CCL11 expression were exclusively mediated by IL-13 signaling via the type 2 IL-4R expressed by nonhematopoietic cells. Conversely, induction of IL-4, CCL24, and eosinophilia was dependent on IL-4 signaling via the type 1 IL-4R expressed by hematopoietic cells. Last, we pharmacologically targeted IL-13Rα1 and established a proof of concept for therapeutic targeting of this pathway in AD. Our data provide mechanistic insight into the differential roles of IL-4, IL-13, and their receptor components in allergic skin and highlight type 2 IL-4R as a potential therapeutic target in AD and other allergic diseases such as asthma and eosinophilic esophagitis.

scholarly journals Simulating trawl herding in flatfish: the role of fish length in behaviour and swimming characteristics

2004 ◽  
Vol 61 (7) ◽  
pp. 1179-1185 ◽  
Author(s):  
Paul D. Winger ◽  
Stephen J. Walsh ◽  
Pingguo He ◽  
Joseph A. Brown
Keyword(s):  
Theoretical Modeling ◽  
Fish Length ◽  
Fish Behaviour ◽  
Settling Behaviour ◽  
Highly Sensitive ◽  
Species Population ◽  
Swimming Kinematics ◽  
Insight Into ◽  
Hippoglossoides Platessoides

Abstract Theoretical modeling indicates that the herding efficiency of flatfish by bottom-trawl sweeps is highly sensitive to subtle changes in fish behaviour. Yet the degree of variation in herding behaviour within a species, population, or individual remains poorly understood because of the difficulty observing and measuring fish behaviour in this region of the gear. The purpose of this study was to simulate herding under laboratory conditions in order to examine the behaviour and swimming characteristics of flatfish. Using a large flume equipped with a moving floor, we examined the effect of fish length on gait use, behaviour, and swimming kinematics in American plaice (Hippoglossoides platessoides). While swimming at a speed comparable to the herding speed of trawl sweeps (0.3 m s−1), smaller plaice (<30 cm) spent a large percentage of time using the kick-swim gait, while larger fish (≥30 cm) preferred cruising. In total, 65% of plaice exhibited settling behaviour, analogous to the swim-and-settle behaviour observed in response to trawl sweeps. The frequency of this behaviour and the distance swum between settles were independent of fish length. Only the frequency of gliding changed with the duration of swimming. Like other teleost species, tailbeat frequency decreased with increasing fish length. The results from this study indicate that fish length affects gait use and swimming kinematics in flatfish, but not the frequency of gliding and settling behaviours. These observations support the hypothesis of size-selective herding and provide further insight into the herding efficiency of trawl sweeps.

Gut microbiota and metabolites in the pathogenesis of endocrine disease

2020 ◽  
Vol 48 (3) ◽  
pp. 915-931 ◽  
Author(s):  
Aline C. Fenneman ◽  
Elena Rampanelli ◽  
Yue S. Yin ◽  
Jesse Ames ◽  
Martin J. Blaser ◽  
...  
Keyword(s):  
Pancreatic Beta Cells ◽  
Intestinal Barrier ◽  
Endocrine Disease ◽  
Disease States ◽  
Microbial Dysbiosis ◽  
Immune Mediated ◽  
Intestinal Barrier Integrity ◽  
Insight Into

Type 1 diabetes (T1D) and Hashimoto's thyroiditis (HT) are the two most common autoimmune endocrine diseases that have rising global incidence. These diseases are caused by the immune-mediated destruction of hormone-producing endocrine cells, pancreatic beta cells and thyroid follicular cells, respectively. Both genetic predisposition and environmental factors govern the onset of T1D and HT. Recent evidence strongly suggests that the intestinal microbiota plays a role in accelerating or preventing disease progression depending on the compositional and functional profile of the gut bacterial communities. Accumulating evidence points towards the interplay between the disruption of gut microbial homeostasis (dysbiosis) and the breakdown of host immune tolerance at the onset of both diseases. In this review, we will summarize the major recent findings about the microbiome alterations associated with T1D and HT, and the connection of these changes to disease states. Furthermore, we will discuss the potential mechanisms by which gut microbial dysbiosis modulates the course of the disease, including disruption of intestinal barrier integrity and microbial production of immunomodulatory metabolites. The aim of this review is to provide broad insight into the role of gut microbiome in the pathophysiology of these diseases.

scholarly journals Discovering the Role of Emotional and Rational Appeals and Hidden Heterogeneity of Consumers in Advertising Copies for Sustainable Marketing

2020 ◽  
Vol 12 (12) ◽  
pp. 5189 ◽  
Author(s):  
Cheong Kim ◽  
Hyeon Gyu Jeon ◽  
Kun Chang Lee
Keyword(s):  
Unobserved Heterogeneity ◽  
Practical Implication ◽  
Marketing Strategies ◽  
Consumer Group ◽  
Sustainable Marketing ◽  
Type 3 ◽  
Insight Into

Advertising copies have been considered as a fundamental strategy for firms to continue sustainable marketing strategies. In order to provide the advancement of previous research and practical implication to marketers in the field for sustainable marketing strategy, this research tried to reveal the role of emotional and rational appeals as well as hidden heterogeneity of consumers in the appeal–value–trust–satisfaction–WOM framework. By applying the PLS-SEM and PLS-POS approach to 230 valid questionnaire samples, we could discover the role of appeals in the framework as well as three types of unobserved heterogeneity among the respondents. Both emotional and rational appeals had significant influences on the value–satisfaction–trust–WOM context. In addition, for hidden consumer traits in advertising copies, we revealed three types of consumer groups: Type 1, the consumer group with a rational orientation (n = 68); Type 2, the group with an emotional orientation (n = 74) and Type 3, the group with a utilitarian orientation. This research provided contributions by offering some insight into ways to establish sustainable marketing strategies in advertisements and to address unobserved heterogeneity consumers in advertising copy appeals.

scholarly journals Unique role of jellyfish in the plankton ecosystem revealed using a global ocean biogeochemical model

2020 ◽  
Author(s):  
Rebecca Mary Wright ◽  
Corinne Le Quéré ◽  
Erik Buitenhuis ◽  
Sophie Pitois ◽  
Mark Gibbons
Keyword(s):  
Marine Ecosystem ◽  
Zooplankton Community ◽  
Plankton Community ◽  
Global Ocean ◽  
Biogeochemical Model ◽  
Unique Role ◽  
Highly Sensitive ◽  
Ocean Biogeochemical Model ◽  
Insight Into

Abstract. Jellyfish are increasingly recognised as important components of the marine ecosystem, yet their specific role is poorly defined compared to that of other zooplankton groups. This paper presents the first global ocean biogeochemical model that includes an explicit representation of jellyfish, and uses the model to gain insight into the influence of jellyfish on the plankton community. The PlankTOM11 model groups organisms into Plankton Functional Types (PFT). The jellyfish PFT is parameterised here based on our synthesis of observations on jellyfish growth, grazing, respiration and mortality rates as functions of temperature and on jellyfish biomass. The distribution of jellyfish is unique compared to that of other PFTs in the model. The jellyfish global biomass of 0.13 PgC is within the observational range, and comparable to the biomass of other zooplankton and phytoplankton PFTs. The introduction of jellyfish in the model has a large direct influence on the crustacean macrozooplankton PFT, and influences indirectly the rest of the plankton ecosystem through trophic cascades. The zooplankton community in PlankTOM11 is highly sensitive to the jellyfish mortality rate, with jellyfish increasingly dominating the zooplankton community as its mortality diminishes. Overall the results suggest that jellyfish play an important and unique role in regulating marine plankton ecosystems, which has been neglected so far. 

The nematode Caenorhabditis elegans synthesizes unusual O-linked glycans: identification of glucose-substituted mucin-type O-glycans and short chondroitin-like oligosaccharides

2001 ◽  
Vol 357 (1) ◽  
pp. 167-182 ◽  
Author(s):  
Yann GUÉRARDEL ◽  
Luis BALANZINO ◽  
Emmanuel MAES ◽  
Yves LEROY ◽  
Bernadette CODDEVILLE ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Nematode Caenorhabditis Elegans ◽  
Free Living ◽  
Experimental Procedure ◽  
C Elegans ◽  
Free Living Nematode ◽  
Multicellular Organisms ◽  
Insight Into

The free-living nematode Caenorhabditis elegans is a relevant model for studies on the role of glycoconjugates during development of multicellular organisms. Several genes coding for glycosyltransferases involved in the synthesis of N- and O-linked glycans have already been isolated, but, apart from repetitive dimers of glycosaminoglycans, no detailed structure of either type of component has been published so far. This study aimed to establish the structures of the major O-glycans synthesized by C. elegans to give an insight into the endogenous glycosyltransferase activities expressed in this organism. By the use of NMR and MS, we have resolved the sequence of seven of these components that present very unusual features. Most of them were characterized by the type-1 core substituted on Gal and/or GalNAc by (β1–4)Glc and (β1–6)Glc residues. Another compound exhibited the GalNAc(β1–4)N-acetylglucosaminitol sequence in the terminal position, to which was attached a tetramer of β-Gal substituted by both Fuc and 2-O-methyl-fucose residues. Our experimental procedure led also to the isolation of glycosaminoglycan-like components and oligomannosyl-type N-glycans. In particular, the data confirmed that C. elegans synthesizes the ubiquitous linker sequence GlcA(β1–3)Gal(β1–3)Gal(β1–4)Xyl.

Igf3: a novel player in fish reproduction†

2021 ◽  
Author(s):  
Jianzhen Li ◽  
Zhiquan Liu ◽  
Tao Kang ◽  
Minghui Li ◽  
Deshou Wang ◽  
...  
Keyword(s):  
Cell Biology ◽  
Fish Reproduction ◽  
Key Factors ◽  
Animal Reproduction ◽  
Physiological Processes ◽  
Igf System ◽  
New Information ◽  
Insight Into

Abstract As in other vertebrates, fish reproduction is tightly controlled by gonadotropin signaling. One of the most perplexing aspects of gonadotropin action on germ cell biology is the restricted expression of gonadotropin receptors in somatic cells of the gonads. Therefore, the identification of factors conveying the action of gonadotropins on germ cells is particularly important for understanding the mechanism of reproduction. Insulin-like growth factors (Igfs) are recognized as key factors in regulating reproduction by triggering a series of physiological processes in vertebrates. Recently, a novel member of Igfs called Igf3 has been identified in teleost. Different from the conventional Igf1 and Igf2 that are ubiquitously expressed in a majority of tissues, Igf3 is solely or highly expressed in the fish gonads. The role of Igf3 in mediating the action of gonadotropin through Igf type 1 receptor on several aspects of oogenesis and spermatogenesis have been demonstrated in several fish species. In this review, we will summarize existing data on Igf3. This new information obtained from Igf3 provides insight into elucidating the molecular mechanism of fish reproduction, and also highlights the importance of Igf system in mediating the action of gonadotropin signaling on animal reproduction.

scholarly journals Ferroptosis, a New Insight Into Acute Lung Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaofang Yin ◽  
Guisong Zhu ◽  
Qian Wang ◽  
Yuan Dong Fu ◽  
Juan Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Therapeutic Potential ◽  
High Morbidity ◽  
Compelling Evidence ◽  
Pathophysiological Process ◽  
Insight Into

Acute lung injury (ALI), a common and critical illness with high morbidity and mortality, is caused by multiple causes. It has been confirmed that oxidative stress plays an important role in the development of ALI. Ferroptosis, a newly discovered programmed cell death in 2012, is characterized by iron-dependent lipid peroxidation and involved in many diseases. To date, compelling evidence reveals the emerging role of ferroptosis in the pathophysiological process of ALI. Here, we review the role of ferroptosis in the pathogenesis of ALI and its therapeutic potential in ALI.

Role of Rhizobium in chickpea (Cicer arietinum) production - A review

2018 ◽  
Vol 38 (01) ◽  
Author(s):  
Zorawar Singh ◽  
Guriqbal Singh ◽  
S. N. Saravaiya
Keyword(s):  
Normal Growth ◽  
Vegetable Crops ◽  
Subsistence Farming ◽  
Weather Factors ◽  
Membrane Selectivity ◽  
Genetic Potential ◽  
Highly Sensitive ◽  
Insight Into

Vegetables are nutritionally rich, high-valued crops and remunerative enough to replace subsistence farming. However, vegetables are highly sensitive to climatic vagaries and sudden irregularities in weather factors at any phase of crop growth can affect the normal growth, flowering, fruit development and subsequently the yield. Grafting in vegetable has emerged as a promising surgical alternative over relatively slow conventional breeding methods aimed at increasing tolerance to biotic and abiotic stresses. It provides an opportunity to transfer some genetic variations of specific traits of rootstocks to influence the phenotype of scion. Thus, genetic potential of various rootstocks in vegetable crops has proven to be a better alternative to chemical sterilants against many soil-borne diseases. The higher physiological activities like antioxidant content, lipoxygenase activity, osmotic adjustment, membrane selectivity, development of adventitious root and aerenchymatous tissue in plants grafted onto potential rootstocks provide broad insight into stress response mechanisms and thus, grafting is proposed to mitigate the adverse impact of climate change on productivity and quality of vegetables crops.

Sign in / Sign up

Export Citation Format

Share Document