scholarly journals New insertions-induced Hb H disease

2021 ◽  
Vol 5 (1) ◽  
pp. 64
Author(s):  
Marzieh Alipour ◽  
Sara Afzali ◽  
Khalil Khashei
Keyword(s):  
Southeast Asia ◽  
Rare Variants ◽  
Point Mutations ◽  
Clinical Importance ◽  
High Impact ◽  
New Findings ◽  
High Incidence ◽  
Hb H Disease ◽  
First Time

In spite of high incidence of α-thalassemia as the most common inherited disorder of hemoglobin (Hb) production in Southeast Asia, the role of point mutations in this aspect not still well known. This fact can lead to missing rare variants of α-thalassemia mutations by the routine screening, which they may need to be screened for possibility of causing Hb H disease. In this study we found two insertions in alpha1 gene which cause to Hb H disease. One of the insertions, 108/109, is a new findings and another one, codon 44, is the mutation which has been followed for the first time. These new molecular findings about changes in α-globin production which results in decreased of hemoglobin (Hb) value, have high-impact clinical importance.

scholarly journals Isoform-Specific Roles of ERK1 and ERK2 in Arteriogenesis

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 38 ◽  
Author(s):  
Nicolas Ricard ◽  
Jiasheng Zhang ◽  
Zhen W. Zhuang ◽  
Michael Simons
Keyword(s):  
Endothelial Cells ◽  
Intracellular Signaling ◽  
Clinical Importance ◽  
Macrophage Infiltration ◽  
Endothelial Cell Proliferation ◽  
Vascular Endothelial ◽  
Ischemic Event ◽  
Intracellular Signaling Pathway ◽  
First Time

Despite the clinical importance of arteriogenesis, this biological process is poorly understood. ERK1 and ERK2 are key components of a major intracellular signaling pathway activated by vascular endothelial growth (VEGF) and FGF2, growth factors critical to arteriogenesis. To investigate the specific role of each ERK isoform in arteriogenesis, we used mice with a global Erk1 knockout as well as Erk1 and Erk2 floxed mice to delete Erk1 or Erk2 in endothelial cells, macrophages, and smooth muscle cells. We found that ERK1 controls macrophage infiltration following an ischemic event. Loss of ERK1 in endothelial cells and macrophages induced an excessive macrophage infiltration leading to an increased but poorly functional arteriogenesis. Loss of ERK2 in endothelial cells leads to a decreased arteriogenesis due to decreased endothelial cell proliferation and a reduced eNOS expression. These findings show for the first time that isoform-specific roles of ERK1 and ERK2 in the control of arteriogenesis.

scholarly journals The Impact of Climate on Southeast Asia, circa 950–1820: New Findings

2012 ◽  
Vol 46 (5) ◽  
pp. 1049-1096 ◽  
Author(s):  
VICTOR LIEBERMAN ◽  
BRENDAN BUCKLEY
Keyword(s):  
Economic Development ◽  
Southeast Asia ◽  
Early Modern ◽  
Tree Ring ◽  
Historical Narrative ◽  
Collaborative Effort ◽  
New Findings ◽  
The Impact ◽  
First Time ◽  
Mainland Southeast Asia

AbstractThe recent discovery of continuous tree-ring series starting as early as 1030 CE has for the first time made possible the reconstruction of historical climates for much of mainland Southeast Asia. Perhaps the most dramatic finding is that wide cyclic fluctuations in the reach and volume of monsoon rains contributed substantially to both the genesis and the collapse of the charter civilizations of Angkor, Pagan, and Dai Viet. Fromcirca1450–1820 climate continued to influence political and economic development, but its impact appears to have diminished both because the amplitude of hydrological fluctuations decreased markedly, and because new sources of power rendered early modern Southeast Asian states more resilient. A pioneering collaborative effort by a historian and a paleoclimatologist, this paper promises three benefits: It can help to solve a variety of local historiographic puzzles, it can facilitate construction of a synchronized historical narrative for mainland Southeast Asia as a whole, and it can aid comparisons between mainland Southeast Asia and other sectors of Eurasia.

Structural Basis for MLL Cxxc Domain Protection against CpG DNA Methylation and the Essential Role of This Function in MLL-AF9 Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 763-763
Author(s):  
Laurie Risner ◽  
Tomasz Cierpicki ◽  
Jolanta Grembecka ◽  
Stephen M Lukasik ◽  
Relja Popovic ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Binding ◽  
Solution Structure ◽  
Conflicts Of Interest ◽  
Point Mutations ◽  
Chromosomal Translocations ◽  
Structural Basis ◽  
Cpg Dna ◽  
First Time

Abstract Abstract 763 MLL is the target of chromosomal translocations which cause leukemias with poor prognosis. All leukemogenic MLL fusion proteins retain the CXXC domain which binds to nonmethylated CpG DNA. We present the solution structure of the MLL CXXC domain in complex with DNA, showing for the first time how the CXXC domain distinguishes nonmethylated from methylated CpG DNA. Based on the structure, we designed point mutations which disrupt DNA binding. Introduction of these mutations into MLL-AF9 results in increased DNA methylation of specific CpG nucleotides in Hoxa9, increased H3K9 methylation, decreased expression of Hoxa9 locus transcripts, loss of immortalization potential, and inability to induce leukemia in mice. These results establish that DNA binding by the CXXC domain and protection against DNA methylation is essential for MLL fusion leukemia. They also validate this interaction as a potential target for therapeutic intervention. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Expression of the Major Porin Gene mspA Is Regulated in Mycobacterium smegmatis

2006 ◽  
Vol 189 (3) ◽  
pp. 958-967 ◽  
Author(s):  
Dietmar Hillmann ◽  
Iris Eschenbacher ◽  
Anja Thiel ◽  
Michael Niederweis
Keyword(s):  
Mycobacterium Smegmatis ◽  
Single Point ◽  
Point Mutations ◽  
Phosphate Limitation ◽  
Transcriptional Fusion ◽  
S1 Nuclease ◽  
Single Point Mutations ◽  
First Time ◽  
Hydrophilic Solutes

ABSTRACT MspA is the major porin of Mycobacterium smegmatis and is important for diffusion of small and hydrophilic solutes across its unique outer membrane. The start point of transcription of the mspA gene was mapped by primer extension and S1 nuclease experiments. The main promoter driving transcription of mspA was identified by single point mutations in lacZ fusions and resembled σA promoters of M. smegmatis. However, a 500-bp upstream fragment including P mspA in a transcriptional fusion with lacZ yielded only low β-galactosidase activity, whereas activity increased 12-fold with a 700-bp fragment. Activation of P mspA by the 200-bp element was almost eliminated by increasing the distance by 14 bp, indicating binding of an activator protein. The chromosomal mspA transcript had a size of 900 bases and was very stable with a half-life of 6 minutes, whereas the stabilities of episomal mspA transcripts with three other 5′ untranslated region (UTRs) were three- to sixfold reduced, indicating a stabilizing role of the native 5′ UTR of mspA. Northern blot experiments revealed that the amount of mspA mRNA was increased under nitrogen limitation but reduced under carbon and phosphate limitation at 42°C in stationary phase in the presence of 0.5 M sodium chloride, 18 mM hydrogen peroxide, and 10% ethanol and at acidic pH. These results show for the first time that M. smegmatis regulates porin gene expression to optimize uptake of certain nutrients and to protect itself from toxic solutes.

scholarly journals Role of the ubiquitin ligase ITCH in clathrin-mediated endocytosis of the epidermal growth factor receptor

2021 ◽  
Author(s):  
Riham Ayoubi ◽  
Peter S. McPherson ◽  
Annie Angers
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Ubiquitin Ligase ◽  
Point Mutations ◽  
Growth Factor Receptor ◽  
Coated Pits ◽  
Epidermal Growth ◽  
First Time

AbstractOnce activated by ligand, epidermal growth factor receptor (EGFR) is endocytosed in clathrin-coated pits. ITCH is an E3 ubiquitin ligase that interacts with and ubiquitinates several proteins involved in clathrin-mediated endocytosis (CME) including endophilin. To further investigate the function of ITCH in EGFR endocytosis, the internalization of fluorescent EGF was measured in ITCH-/- HeLa cells. In the absence of ITCH, there was a significant decrease in the CME of EGF. Rescue experiments using wild-type ITCH confirmed the importance of the protein for normal EGF uptake. ITCH point mutations that disrupt the interaction of ITCH with endophilin failed to rescue the defects in EGFR uptake, as did a non-catalytic form of ITCH. ITCH-/- cells also displayed a delay in the rate of phospho-EGFR degradation as well as prolonged ERK1/2 signaling. Our study uncovers a pathway regulating EGFR trafficking and reveals for the first time that the protein ITCH is required for CME of EGFR.

Psychological Resilience Provides No Independent Protection From Suicidal Risk

Crisis ◽  
2016 ◽  
Vol 37 (2) ◽  
pp. 130-139 ◽  
Author(s):  
Danica W. Y. Liu ◽  
A. Kate Fairweather-Schmidt ◽  
Richard Burns ◽  
Rachel M. Roberts ◽  
Kaarin J. Anstey
Keyword(s):  
Risk Factors ◽  
Well Being ◽  
Current Status ◽  
Psychological Resilience ◽  
Cross Sectional ◽  
Life Project ◽  
Resilience Factors ◽  
First Time

Abstract. Background: Little is known about the role of resilience in the likelihood of suicidal ideation (SI) over time. Aims: We examined the association between resilience and SI in a young-adult cohort over 4 years. Our objectives were to determine whether resilience was associated with SI at follow-up or, conversely, whether SI was associated with lowered resilience at follow-up. Method: Participants were selected from the Personality and Total Health (PATH) Through Life Project from Canberra and Queanbeyan, Australia, aged 28–32 years at the first time point and 32–36 at the second. Multinomial, linear, and binary regression analyses explored the association between resilience and SI over two time points. Models were adjusted for suicidality risk factors. Results: While unadjusted analyses identified associations between resilience and SI, these effects were fully explained by the inclusion of other suicidality risk factors. Conclusion: Despite strong cross-sectional associations, resilience and SI appear to be unrelated in a longitudinal context, once risk/resilience factors are controlled for. As independent indicators of psychological well-being, suicidality and resilience are essential if current status is to be captured. However, the addition of other factors (e.g., support, mastery) makes this association tenuous. Consequently, resilience per se may not be protective of SI.

Synergetic Theory of Document in Evolution of Document Science

2018 ◽  
pp. 1060-1068
Author(s):  
Galina A. Dvoenosova ◽  
Keyword(s):  
Social Role ◽  
Scientific Study ◽  
Self Organization ◽  
Universal Theory ◽  
Social Self ◽  
Social Goal ◽  
The Social ◽  
Synergetic Theory ◽  
First Time

The article assesses synergetic theory of document as a new development in document science. In information society the social role of document grows, as information involves all members of society in the process of documentation. The transformation of document under the influence of modern information technologies increases its interest to representatives of different sciences. Interdisciplinary nature of document as an object of research leads to an ambiguous interpretation of its nature and social role. The article expresses and contends the author's views on this issue. In her opinion, social role of document is incidental to its being a main social tool regulating the life of civilized society. Thus, the study aims to create a scientific theory of document, explaining its nature and social role as a tool of social (goal-oriented) action and social self-organization. Substantiation of this idea is based on application of synergetics (i.e., universal theory of self-organization) to scientific study of document. In the synergetic paradigm, social and historical development is seen as the change of phases of chaos and order, and document is considered a main tool that regulates social relations. Unlike other theories of document, synergetic theory studies document not as a carrier and means of information transfer, but as a unique social phenomenon and universal social tool. For the first time, the study of document steps out of traditional frameworks of office, archive, and library. The document is placed on the scales with society as a global social system with its functional subsystems of politics, economy, culture, and personality. For the first time, the methods of social sciences and modern sociological theories are applied to scientific study of document. This methodology provided a basis for theoretical vindication of nature and social role of document as a tool of social (goal-oriented) action and social self-organization. The study frames a synergetic theory of document with methodological foundations and basic concepts, synergetic model of document, laws of development and effectiveness of document in the social continuum. At the present stage of development of science, it can be considered the highest form of theoretical knowledge of document and its scientific explanatory theory.

Materials to the lichen flora of Samurskiy Ridge (high mountainous Dagestan)

2018 ◽  
Vol 52 (2) ◽  
pp. 397-406
Author(s):  
A. B. Ismailov ◽  
G. P. Urbanavichus
Keyword(s):  
North Caucasus ◽  
Lichenicolous Fungi ◽  
Greater Caucasus ◽  
Altitudinal Range ◽  
The North ◽  
New Findings ◽  
Mountainous Landscapes ◽  
First Time ◽  
Lichen Flora

The lichens and lichenicolous fungi of high mountainous landscapes of Samurskiy Ridge were studied in altitudinal range 2400–3770 m a. s. l. for the first time and 112 species are recorded. Among them 33 species, 10 genera (Arthrorhaphis, Baeomyces, Calvitimela, Epilichen, Lambiella, Psorinia, Rufoplaca, Sagedia, Sporastatia, Tremolecia) and 4 families (Anamylopsoraceae, Arthrorhaphidaceae, Baeomycetaceae, Hymeneliaceae) are new for Dagestan, six species (Buellia uberior, Carbonea atronivea, Lecanora atrosulphurea, Lecidea fuliginosa, L. swartzioidea, Rhizoplaca subdiscrepans) are reported for the first time for the Greater Caucasus and two species (Acarospora subpruinata and Rhizocarpon postumum) — for the North Caucasus. Most of the new findings were collected from 3500–3770 m a. s. l.

Physical Warmth Attenuates Ethnocentric Bias under Mortality Salience: An Embodied Terror Management Perspective

2020 ◽  
Author(s):  
Armand Chatard ◽  
Margaux Renoux ◽  
Jean Monéger ◽  
Leila Selimbegovic
Keyword(s):  
Mortality Salience ◽  
Terror Management ◽  
Negative Consequences ◽  
Defensive Reaction ◽  
Worldview Defense ◽  
Management Perspective ◽  
Physical Warmth ◽  
Alternative Means ◽  
First Time

Research indicates that individuals often deal with mortality salience by affirming beliefs in national or cultural superiority (worldview defense). Because worldview defense may be associated with negative consequences (discrimination), it is important to identify alternative means to deal with death-related thoughts. In line with an embodied terror management perspective, we evaluate for the first time the role of physical warmth in reducing defensive reaction to mortality salience. We predicted that, like social affiliation (social warmth), physical warmth could reduce worldview defense when mortality is salient. In this exploratory (preregistered) study, 202 French participants were primed with death-related thoughts, or an aversive control topic, in a heated room or a non-heated room. The main outcome was worldview defense (ethnocentric bias). We found no main effect of mortality salience on worldview defense. However, physical warmth reduced worldview defense when mortality was salient. Implications for an embodied terror management perspective are discussed.

Relationship between big five personality model and abusive supervision

2019 ◽  
Vol 12 (2) ◽  
Author(s):  
Bibi Tahira ◽  
Naveed Saif ◽  
Muhammad Haroon ◽  
Sadaqat Ali
Keyword(s):  
Big Five ◽  
Abusive Supervision ◽  
State Universities ◽  
Big Five Personality ◽  
Big Five Model ◽  
The Impact ◽  
First Time ◽  
Supervisor Behavior ◽  
Moderating Role

The current study tries to understand the diverse nature of relationship between personality Big Five Model (PBFM) and student's perception of abusive supervision in higher education institutions of Khyber Pakhtoonkhwa Pakistan. Data was collected in dyads i.e. (supervisors were asked to rate their personality attributes while student were asked to rate the supervisor behavior) through adopted construct. For this purpose, data was collected from three government state universities and one Private Sector University. The focus was on MS/M.Phill and PhD student and their supervisors of the mentioned universities. After measuring normality and validity regression analysis was conducted to assess the impact of supervisor personality characteristics that leads to abusive supervision. Findings indicate interestingly that except agreeableness other four attributes of (PBFM) are play their role for abusive supervision. The results are novel in the nature as for the first time Neuroticism, openness to experience, extraversion and conscientiousness are held responsible for the abusive supervision. The study did not explore the demographic characteristics, and moderating role of organizational culture, justice and interpersonal deviances to understand the strength of relationship in more detail way. Keywords: Personality big five model, abusive supervision, HEIs

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