scholarly journals Probing the Modularity of Megasynthases by Rational Engineering of a Fatty Acid Synthase (FAS) Type I

2018 ◽  
Author(s):  
Alexander Rittner ◽  
Karthik S. Paithankar ◽  
David Drexler ◽  
Aaron Himmler ◽  
Martin Grininger
Keyword(s):  
Fatty Acid Synthase ◽  
Fundamental Property ◽  
Catalytic Efficiency ◽  
Sequence Information ◽  
Type I ◽  
The Novel ◽  
Strongly Coupled ◽  
Rational Engineering ◽  
The Family ◽  
Biological Entities

AbstractModularity is an aspect of a decomposable system with a coordinating authority that acts as a glue which holds the loosely held components. These multi-component entities (“modules”) facilitate rewiring into different designs allowing for change. Such modular character is a fundamental property of many biological entities, especially the family of megasynthases such as polyketide synthases (PKSs). The ability of these PKSs to produce diverse product spectra is strongly coupled to their broad architectural modularity. Decoding the molecular basis of modularity, i.e. identifying the folds and domains that comprise the modules as well as understanding constrains of the assembly of modules, is of utmost importance for harnessing megasynthases for the synthesis of designer compounds. In this study, we exploit the close semblance between PKSs and animal FAS to re-engineer animal FAS to probe the modularity of the FAS/PKS family. Guided by structural and sequence information, we truncate and dissect animal FAS into its components, and reassemble them to generate new PKS-like modules as well as bimodular constructs. The novel engineered modules resemble all four common module types of PKSs and demonstrate that this approach can be a powerful tool to create higher catalytic efficiency. Our data exemplify the inherent plasticity and robustness of the overall FAS/PKS fold, and open new avenues to explore FAS-based biosynthetic pathways for custom compound design.

scholarly journals Probing the modularity of megasynthases by rational engineering of a fatty acid synthase Type I

2018 ◽  
Vol 28 (2) ◽  
pp. 414-428 ◽  
Author(s):  
Alexander Rittner ◽  
Karthik S. Paithankar ◽  
David Jan Drexler ◽  
Aaron Himmler ◽  
Martin Grininger
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Type I ◽  
Rational Engineering

A Mutation in the Protein S Pseudogene Is Linked to Protein S Deficiency in a Thrombophilic Family

1989 ◽  
Vol 62 (03) ◽  
pp. 897-901 ◽  
Author(s):  
Hans K Ploos van Amstel ◽  
Pieter H Reitsma ◽  
Karly Hamulyák ◽  
Christine E M de Die-Smulders ◽  
Pier M Mannucci ◽  
...  
Keyword(s):  
Total Protein ◽  
Protein S ◽  
Southern Analysis ◽  
Type I ◽  
Protein S Deficiency ◽  
S Deficiency ◽  
The Family ◽  
Dna Pattern ◽  
Deficiency Type ◽  
S Genes

SummaryProbands from 15 unrelated families with hereditary protein S deficiency type I, that is having a plasma total protein S concentration fifty percent of normal, were screened for abnormalities in their protein S genes by Southern analysis. Two probands were found to have a deviating DNA pattern with the restriction enzyme Mspl. In the two patients the alteration concerned the disappearance of a Mspl restriction site, CCGG, giving rise to an additional hybridizing Mspl fragment.Analysis of relatives of both probands showed that in one family the mutation does not co-segregate with the phenotype of reduced plasma protein S. In the family of the other proband, however, complete linkage between the mutated gene pattern and the reduced total protein S concentration was found: 12 heterozygous relatives showed the additional Mspl fragment but none of the investigated 26 normal members of the family. The mutation is shown to reside in the PSβ gene, the inactive protein S gene. The cause of type I protein S deficiency, a defect PSα gene has escaped detection by Southern analysis. No recombination has occurred between the PSα gene and the PSβ gene in 23 informative meioses. This suggests that the two protein S genes, located near the centromere of chromosome 3, are within 4 centiMorgan of each other.

SISTEM SOSIAL ALA NIKLASH LUHMAN DALAM NOVEL SEPERTIGA MALAM DI MANHATTAN KARYA ARUMI E

2019 ◽  
Vol 7 (2) ◽  
pp. 49
Author(s):  
Anton Wahyudi
Keyword(s):  
Social System ◽  
System Approach ◽  
Research Method ◽  
Qualitative Method ◽  
The Novel ◽  
Original Culture ◽  
The Family ◽  
Data Source ◽  
Social System Approach ◽  
Fictional Story

The novel Sepertiga Malam di Manhattan by Arumi E is very interesting to study. This novel is a novel about the struggle of a family to get happiness. This novel is the Arumi E's 27th newest novel. The struggle in this novel is to make the family happy, expecting for the baby. Before writing the novel, Arumi E did a research in the places written in the novel to achieve a very interesting fictional story and most of this story was taken from the traveling results so it was so interesting. The objective of this research is to describe (1) the Autopoetic System in the novel Sepertiga MalamdiManhattan by Arumi E. (2) The differentiation system in the Novel Sepertiga Malamdi Manhattan by Arumi E.The research method used is in the form of a descriptive qualitative method that uses a social system approach. The method used by the researcher is the dialectical method. The data source used in this research is the novel Sepertiga Malamdi Manhattan by Arumi E, published by Gramedia publisher in 2018. The data collection in this study uses the steps of reading the novel. To collect data, the researcher use any instrument.There are two results of the study: (1) The autopoetic system in the novel Sepertiga MalamdiManhattan by Arumi E. is concerning to some characters who have their own beliefs or rules in their lives who do not want to follow the rules of others, they are more confident in their own way to success and purpose of life. (2) The system of differentiation in the novel Sepertiga Malamdi Manhattan by Arumi E. is covering the handling of changes in the environment, the characters are able to adapt to the new environment, which has a different culture from the original culture. This shows evidence of the system autopoetic and differentiation in the novel Sepertiga MalamdiManhattan by Arumi E.

Buried Narratives: Exhuming the Mother's Story in Oliver Twist

2018 ◽  
Vol 8 (3) ◽  
pp. 247-266
Author(s):  
Michelle L. Wilson
Keyword(s):  
Social Change ◽  
Maternal Inheritance ◽  
The Novel ◽  
Poor Law ◽  
The Family ◽  
The Law ◽  
First Time ◽  
Critical Consideration

Initially, Oliver Twist (1839) might seem representative of the archetypal male social plot, following an orphan and finding him a place by discovering the father and settling the boy within his inheritance. But Agnes Fleming haunts this narrative, undoing its neat, linear transmission. This reconsideration of maternal inheritance and plot in the novel occurs against the backdrop of legal and social change. I extend the critical consideration of the novel's relationship to the New Poor Law by thinking about its reflection on the bastardy clauses. And here, of course, is where the mother enters. Under the bastardy clauses, the responsibility for economic maintenance of bastard children was, for the first time, legally assigned to the mother, relieving the father of any and all obligation. Oliver Twist manages to critique the bastardy clauses for their release of the father, while simultaneously embracing the placement of the mother at the head of the family line. Both Oliver and the novel thus suggest that it is the mother's story that matters, her name through which we find our own. And by containing both plots – that of the father and the mother – Oliver Twist reveals the violence implicit in traditional modes of inheritance in the novel and under the law.

Breaking Free

2017 ◽  
Author(s):  
Deirdre David
Keyword(s):  
United States ◽  
The United States ◽  
The Novel ◽  
Male Homosexuality ◽  
Domestic Life ◽  
The Family

In the mid- to late 1950s, Pamela emerged as a critically acclaimed novelist, particularly after the family returned to London. In perhaps her best-known novel, The Unspeakable Skipton, she explores the life of a paranoid writer who sponges on English visitors to Bruges. The novel was hailed for its wit and sensitive depiction of the life of a writer. She also published a fine study of a London vicar martyred in marriage to a vain and selfish wife: The Humbler Creation is remarkable for its incisive and empathetic depiction of male despair. The Last Resort sealed her distinction as a brilliant novelist of domestic life in its frank depiction of male homosexuality. While continuing to publish fiction, Pamela maintained her reputation as a deft reviewer. In 1954, she and Charles travelled to the United States—the first of many trips that were to follow.

Mansfield Park

2008 ◽  
Author(s):  
Jane Austen ◽  
Jane Stabler
Keyword(s):  
The Novel ◽  
Mansfield Park ◽  
Sexual Jealousy ◽  
The Family ◽  
The World ◽  
The Face

‘Me!’ cried Fanny … ‘Indeed you must excuse me. I could not act any thing if you were to give me the world. No, indeed, I cannot act.’ At the age of ten, Fanny Price leaves the poverty of her Portsmouth home to be brought up among the family of her wealthy uncle, Sir Thomas Bertram, in the chilly grandeur of Mansfield Park. There she accepts her lowly status, and gradually falls in love with her cousin Edmund. When the dazzling and sophisticated Henry and Mary Crawford arrive, Fanny watches as her cousins become embroiled in rivalry and sexual jealousy. As the company starts to rehearse a play by way of entertainment, Fanny struggles to retain her independence in the face of the Crawfords’ dangerous attractions; and when Henry turns his attentions to her, the drama really begins… This new edition does full justice to Austen’s complex and subtle story, placing it in its Regency context and elucidating the theatrical background that pervades the novel.

scholarly journals REMAXINT: a two-mode clustering-based method for statistical inference on two-way interaction

2021 ◽  
Author(s):  
Zaheer Ahmed ◽  
Alberto Cassese ◽  
Gerard van Breukelen ◽  
Jan Schepers
Keyword(s):  
Null Hypothesis ◽  
Type I Error ◽  
Type I ◽  
The Novel ◽  
Simulation Studies ◽  
Test Statistic ◽  
Clustering Model ◽  
Novel Method ◽  
Main Effects ◽  
Empirical Case Studies

AbstractWe present a novel method, REMAXINT, that captures the gist of two-way interaction in row by column (i.e., two-mode) data, with one observation per cell. REMAXINT is a probabilistic two-mode clustering model that yields two-mode partitions with maximal interaction between row and column clusters. For estimation of the parameters of REMAXINT, we maximize a conditional classification likelihood in which the random row (or column) main effects are conditioned out. For testing the null hypothesis of no interaction between row and column clusters, we propose a $$max-F$$ m a x - F test statistic and discuss its properties. We develop a Monte Carlo approach to obtain its sampling distribution under the null hypothesis. We evaluate the performance of the method through simulation studies. Specifically, for selected values of data size and (true) numbers of clusters, we obtain critical values of the $$max-F$$ m a x - F statistic, determine empirical Type I error rate of the proposed inferential procedure and study its power to reject the null hypothesis. Next, we show that the novel method is useful in a variety of applications by presenting two empirical case studies and end with some concluding remarks.

scholarly journals Nuclear cGAS: sequestration and beyond

2021 ◽  
Author(s):  
Juli Bai ◽  
Feng Liu
Keyword(s):  
Innate Immune ◽  
Complex Nature ◽  
Type I ◽  
Replication Forks ◽  
The Novel ◽  
Nuclear Function ◽  
Double Stranded Dna ◽  
Open Questions ◽  
Established Role ◽  
Dependent Signaling Pathway

AbstractThe cyclic GMP-AMP (cGAMP) synthase (cGAS) has been identified as a cytosolic double stranded DNA sensor that plays a pivotal role in the type I interferon and inflammation responses via the STING-dependent signaling pathway. In the past several years, a growing body of evidence has revealed that cGAS is also localized in the nucleus where it is associated with distinct nuclear substructures such as nucleosomes, DNA replication forks, the double-stranded breaks, and centromeres, suggesting that cGAS may have other functions in addition to its role in DNA sensing. However, while the innate immune function of cGAS is well established, the non-canonical nuclear function of cGAS remains poorly understood. Here, we review our current understanding of the complex nature of nuclear cGAS and point to open questions on the novel roles and the mechanisms of action of this protein as a key regulator of cell nuclear function, beyond its well-established role in dsDNA sensing and innate immune response.

scholarly journals Delayed diagnosis of Peutz–Jeghers syndrome due to pathological information loss or mistake in family/personal history

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yu-Liang Jiang ◽  
Xiao-Dong Xu ◽  
Bai-Rong Li ◽  
En-Da Yu ◽  
Zi-Ye Zhao ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Novel Mutation ◽  
Delayed Diagnosis ◽  
Personal History ◽  
Pathological Examination ◽  
The Novel ◽  
Novel Mutations ◽  
The Family ◽  
Genetic Level ◽  
Peutz Jeghers Syndrome

Abstract Objective To report Peutz–Jeghers syndrome (PJS) cases with non-definitive clues in the family or personal history and finally diagnosed through pathological examination and STK11 gene mutation test. Clinical presentation and intervention PJS was suspected in 3 families with tortuous medical courses. Two of them had relatives departed due to polyposis or colon cancer without pathological results, and the other one had been diagnosed as hyperplastic polyposis before. Diagnosis of PJS was confirmed by endoscopy and repeated pathological examinations, and the STK11 mutation test finally confirmed the diagnosis at genetic level, during which 3 novel mutation were detected (536C > A, 373_374insA, 454_455insGGAGAAGCGTTTCCCAGTGTGCC). Conclusion Early diagnosis of PJS is important and may be based on a family history with selective features among family members, and the pathological information is the key. The novel mutations also expand the STK11 variant spectrum.

scholarly journals The intersection of COVID-19 and cancer: signaling pathways and treatment implications

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhi Zong ◽  
Yujun Wei ◽  
Jiang Ren ◽  
Long Zhang ◽  
Fangfang Zhou
Keyword(s):  
Signaling Pathways ◽  
Health Concern ◽  
Type I ◽  
The Novel ◽  
Checkpoint Signaling ◽  
Patients With Cancer ◽  
Advantages And Disadvantages ◽  
Anticancer Treatment ◽  
Severe Infections ◽  
Novel Coronavirus

AbstractThe outbreak of the novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a serious public health concern. Patients with cancer have been disproportionately affected by this pandemic. Increasing evidence has documented that patients with malignancies are highly susceptible to severe infections and mortality from COVID-19. Recent studies have also elucidated the molecular relationship between the two diseases, which may not only help optimize cancer care during the pandemic but also expand the treatment for COVID-19. In this review, we highlight the clinical and molecular similarities between cancer and COVID-19 and summarize the four major signaling pathways at the intersection of COVID-19 and cancer, namely, cytokine, type I interferon (IFN-I), androgen receptor (AR), and immune checkpoint signaling. In addition, we discuss the advantages and disadvantages of repurposing anticancer treatment for the treatment of COVID-19.

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