Modular arrangements of sequence motifs determine the functional diversity of KDM proteins

Author(s):  
Zerong Wang ◽  
Dongyang Liu ◽  
Baofang Xu ◽  
Ruixia Tian ◽  
Yongchun Zuo

Abstract Histone lysine demethylases (KDMs) play a vital role in regulating chromatin dynamics and transcription. KDM proteins are given modular activities by its sequence motifs with obvious roles division, which endow the complex and diverse functions. In our review, according to functional features, we classify sequence motifs into four classes: catalytic motifs, targeting motifs, regulatory motifs and potential motifs. JmjC, as the main catalytic motif, combines to Fe2+ and α-ketoglutarate by residues H-D/E-H and S-N-N/Y-K-N/Y-T/S. Targeting motifs make catalytic motifs recognize specific methylated lysines, such as PHD that helps KDM5 to demethylate H3K4me3. Regulatory motifs consist of a functional network. For example, NLS, Ser-rich, TPR and JmjN motifs regulate the nuclear localization. And interactions through the CW-type-C4H2C2-SWIRM are necessary to the demethylase activity of KDM1B. Additionally, many conservative domains that have potential functions but no deep exploration are reviewed for the first time. These conservative domains are usually amino acid-rich regions, which have great research value. The arrangements of four types of sequence motifs generate that KDM proteins diversify toward modular activities and biological functions. Finally, we draw a blueprint of functional mechanisms to discuss the modular activity of KDMs.

2021 ◽  
Vol 7 (3) ◽  
pp. 38
Author(s):  
Alexandra Korotaeva ◽  
Danzan Mansorunov ◽  
Natalya Apanovich ◽  
Anna Kuzevanova ◽  
Alexander Karpukhin

Neuroendocrine neoplasms (NEN) are infrequent malignant tumors of a neuroendocrine nature that arise in various organs. They occur most frequently in the lungs, intestines, stomach and pancreas. Molecular diagnostics and prognosis of NEN development are highly relevant. The role of clinical biomarkers can be played by microRNAs (miRNAs). This work is devoted to the analysis of data on miRNA expression in NENs. For the first time, a search for specificity or a community of their functional characteristics in different types of NEN was carried out. Their properties as biomarkers were also analyzed. To date, more than 100 miRNAs have been characterized as differentially expressed and significant for the development of NEN tumors. Only about 10% of the studied miRNAs are expressed in several types of NEN; differential expression of the remaining 90% was found only in tumors of specific localizations. A significant number of miRNAs have been identified as potential biomarkers. However, only a few miRNAs have values that characterized their quality as markers. The analysis demonstrates the predominant specific expression of miRNA in each studied type of NEN. This indicates that miRNA’s functional features are predominantly influenced by the tissue in which they are formed.


2021 ◽  
Author(s):  
Martijn A. Wijnhoven

Mail armour (commonly mislabelled 'chainmail') was used for more than two millennia on the battlefield. After its invention in the Iron Age, mail rapidly spread all over Europe and beyond. The Roman army, keen on new military technology, soon adopted mail armour and used it successfully for centuries. Its history did not stop there and mail played a vital role in warfare during the Middle Ages up to the Early Modern Period. Given its long history, one would think mail is a well-documented material, but that is not the case. For the first time, this books lays a solid foundation for the understanding of mail armour and its context through time. It applies a long-term multi-dimensional approach to extract a wealth of as yet untapped information from archaeological, iconographic and written sources. This is complemented with technical insights on the mail maker’s chaîne opératoire.


2019 ◽  
Author(s):  
Hal Tily ◽  
Ally Perlina ◽  
Eric Patridge ◽  
Stephanie Gline ◽  
Matvey Genkin ◽  
...  

AbstractLimiting post-meal glycemic response is an important factor in reducing the risk of chronic metabolic diseases, and contributes to significant health benefits in people with elevated levels of blood sugar. In this study, we collected gut microbiome activity (i.e., metatranscriptomic) data and measured the glycemic responses of 550 adults who consumed more than 30,000 meals from omnivore or vegetarian/gluten-free diets. We demonstrate that gut microbiome activity makes a statistically significant contribution to individual variation in glycemic response, in addition to anthropometric factors and the nutritional composition of foods. We describe predictive models (multilevel mixed-effects regression and gradient boosting machine) of variation in glycemic response among individuals ingesting the same foods. We introduce functional features aggregated from microbial activity data as candidates for association with mechanisms of glycemic control. In summary, we demonstrate for the first time that metatranscriptomic activity of the gut microbiome is correlated with glycemic response among adults.


Algologia ◽  
2020 ◽  
Vol 30 (4) ◽  
pp. 440-451
Author(s):  
M. Shamina ◽  

Cyanobacteria are organisms which play a vital role in various molecular and biotechnological aspects in food industry, agriculture, pharmaceuticals, neutraceuticals, biofuel production, etc., it is necessary to understand its adaptability to various environmental conditions. Furthermore it is equally important to discover new cyanobacterial taxa and with it occasional changes in taxonomic classification, thus the author set out to study cyanobacteria in extreme climatic conditions of desert, where temperatures are mostly above 45 oC. The taxonomic composition of cyanobacteria of Masirah Island, Sultanate of Oman, was studied for the first time. The studied samples were collected during the period of 2017–2019. The ten samples belonged to two orders: Oscillatoriales Schaffner and Synechococcales L.Hoffmann, Komárek & J.Kastovsky. All of them were filamentous non-heterocyst forms. Three species belonged to the genus Leptolyngbya Anagn. & Komárek, the genera Oscillatoria Vaucher ex Gomont and Lyngbya C.Agardh ex Gomont were represented by two species each, while the genera Pseudanabena Lauterborn, Planktolyngbya Anagn. & Komárek and Geitlerinema (Anagn. & Komárek) Anagn. were one species.


2021 ◽  
Author(s):  
Na Li ◽  
Zehan Li ◽  
Lin Fu ◽  
Ming Yan ◽  
Yanqiu Wang ◽  
...  

Abstract BackgroundStem cells from the apical papilla (SCAPs) are important for tooth root development and regeneration of root dentin. Here, we examined the expression of programmed cell death protein-1 (PD-1) in SCAPs and investigated the effect of PD-1 on odontogenic and osteogenic differentiation and the relationship between PD-1 and cell differentiation and SHP2/NF-κB signals.MethodsSCAPs were obtained culture in the related medium. The proliferation ability was evaluated by cell counting kit 8 and 5‐ethynyl‐20‐deoxyuridine (EdU) assay. Alkaline phosphatase (ALP) activity assay, ALP staining, western blot, real-time RT-PCR, Alizarin Red S staining, and immunofluorescence staining were performed to explore the osteo/odontogenic potential and the involvement of SHP2/NF-κB pathways. Besides, we transplanted SCAPs component into mouse calvaria defects to evaluate osteogenesis in vivo. ResultsWe found that human SCAPs expressed PD-1 for the first time. PD-1 knockdown enhanced the osteo/odontogenic differentiation of SCAPs by suppressing SHP2 pathway and activating NF-κB pathway. Overexpression of PD-1 inhibited the osteogenesis and odontogenesis of SCAPs via activation of SHP2 signal and inhibition of NF-κB pathway. ConclusionPD-1 activated SHP2 signal to block NF-κB signal and then played a vital role in osteo/odontogenic differentiation of SCAPs.


2020 ◽  
pp. 108128652096564
Author(s):  
Yuanjie Huang

Dislocations and dislocation dynamics are the cores of material plasticity. In this work, the electric features of dislocations were investigated theoretically. An intrinsic electric field around a single dislocation was revealed. In addition to the well-known Peach–Koehler force, it was established that an important intrinsic electric force exists between dislocations, which is uncovered here for the first time and has been neglected since the discovery of dislocations. The electric forces may be large and sometimes could exceed the Peach–Koehler force for metals and some dielectric materials with large dielectric constant. Therefore, the electric force is anticipated to play a vital role in dislocation dynamics and material plasticity. Moreover, an external electric field could exert an electric force on dislocations and a threshold electric field was subsequently discovered above which this force enables dislocations to glide. Interestingly, it was found that some dislocations move in one direction, but others move in reverse in an identical electric field, which is in agreement with experimental observations. Despite dislocation motion under an electric field, to one’s surprise, both edge and screw dislocations do not carry net charges by themselves, which may tackle the long-standing puzzle on the charges of dislocations. These findings may supply people with new fundamental knowledge on dislocations as well as dislocation dynamics, and may assist people in understanding related phenomena.


2000 ◽  
Vol 151 (7) ◽  
pp. 1513-1524 ◽  
Author(s):  
Ruwanthi N. Gunawardane ◽  
Ona C. Martin ◽  
Kan Cao ◽  
Lijun Zhang ◽  
Kimberly Dej ◽  
...  

The γ-tubulin ring complex (γTuRC) is important for microtubule nucleation from the centrosome. In addition to γ-tubulin, the Drosophila γTuRC contains at least six subunits, three of which [Drosophila gamma ring proteins (Dgrips) 75/d75p, 84, and 91] have been characterized previously. Dgrips84 and 91 are present in both the small γ-tubulin complex (γTuSC) and the γTuRC, while the remaining subunits are found only in the γTuRC. To study γTuRC assembly and function, we first reconstituted γTuSC using the baculovirus expression system. Using the reconstituted γTuSC, we showed for the first time that this subcomplex of the γTuRC has microtubule binding and capping activities. Next, we characterized two new γTuRC subunits, Dgrips128 and 163, and showed that they are centrosomal proteins. Sequence comparisons among all known γTuRC subunits revealed two novel sequence motifs, which we named grip motifs 1 and 2. We found that Dgrips128 and 163 can each interact with γTuSC. However, this interaction is insufficient for γTuRC assembly.


2004 ◽  
Vol 32 (5) ◽  
pp. 715-720 ◽  
Author(s):  
I. Dreveny ◽  
V.E. Pye ◽  
F. Beuron ◽  
L.C. Briggs ◽  
R.L. Isaacson ◽  
...  

The AAA (ATPase associated with various cellular activities) ATPase, p97, is a hexameric protein of chaperone-like function, which has been reported to interact with a number of proteins of seemingly unrelated functions. For the first time, we report a classification of these proteins and aim to elucidate any common structural or functional features they may share. The interactors are grouped into those containing ubiquitin regulatory X domains, which presumably bind to p97 in the same way as the p47 adaptor, and into non-ubiquitin regulatory X domain proteins of different functional subgroups that may employ a different mode of interaction (assuming they also bind directly to p97 and are not experimental artifacts). Future studies will show whether interacting proteins direct p97 to different cellular pathways or a common one and structural elucidation of these interactions will be crucial in understanding these underlying functions.


2001 ◽  
Vol 75 (4) ◽  
pp. 1611-1619 ◽  
Author(s):  
Thomas Pfister ◽  
Eckard Wimmer

ABSTRACT Southampton virus (SHV) is a member of the Norwalk-like viruses (NLVs), one of four genera of the family Caliciviridae. The genome of SHV contains three open reading frames (ORFs). ORF 1 encodes a polyprotein that is autocatalytically processed into six proteins, one of which is p41. p41 shares sequence motifs with protein 2C of picornaviruses and superfamily 3 helicases. We have expressed p41 of SHV in bacteria. Purified p41 exhibited nucleoside triphosphate (NTP)-binding and NTP hydrolysis activities. The NTPase activity was not stimulated by single-stranded nucleic acids. SHV p41 had no detectable helicase activity. Protein sequence comparison between the consensus sequences of NLV p41 and enterovirus protein 2C revealed regions of high similarity. According to secondary structure prediction, the conserved regions were located within a putative central domain of alpha helices and beta strands. This study reveals for the first time an NTPase activity associated with a calicivirus-encoded protein. Based on enzymatic properties and sequence information, a functional relationship between NLV p41 and enterovirus 2C is discussed in regard to the role of 2C-like proteins in virus replication.


Author(s):  
Tunahan Altintop ◽  
Ronald R. Yager ◽  
Diyar Akay ◽  
Fatih Emre Boran ◽  
Muhammet Ünal

It is now well recognized that knowledge extracted from rich healthcare data play a vital role for delivery, management and planning of healthcare services. So far, however, there is not much study done on the domain of operational and financial healthcare data since, up to now, a great deal of works are dedicated to clinical/medical healthcare data for the purposes of diagnosis and treatment of diseases. In this paper, an attempt is made, by applying fuzzy linguistic summarization, for the first time to discover knowledge from operational and financial healthcare data. Fuzzy linguistic summarization, in its simplest term, provides natural language based summaries from a dataset in a human consistent way along with a degree of truth attached to each summary. While basically valuable, its benefit can be increased by only generating summaries with a degree of truth above than an indicated threshold value. A genetic algorithm is developed within this context in order to eliminate less promising and useless linguistic summaries. We assess the proposed approach experimentally on a real data and evaluate the generated summaries to gain actionable insights from them.


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