scholarly journals Mitochondrial genome variation in male LHON patients with the m.11778G > A mutation

2020 ◽  
Vol 35 (8) ◽  
pp. 1317-1327
Author(s):  
Agnieszka Piotrowska-Nowak ◽  
Maciej R. Krawczyński ◽  
Ewa Kosior-Jarecka ◽  
Anna M. Ambroziak ◽  
Magdalena Korwin ◽  
...  
Keyword(s):  
Vision Loss ◽  
Mitochondrial Disorder ◽  
Point Mutations ◽  
Leber Hereditary Optic Neuropathy ◽  
Modifying Factors ◽  
Mtdna Variation ◽  
Negative Effect ◽  
Generation Sequencing ◽  
Mtdna Haplogroup

Abstract Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder with symptoms limited to a single tissue, optic nerve, resulting in vision loss. In the majority of cases it is caused by one of three point mutations in mitochondrial DNA (mtDNA) but their presence is not sufficient for disease development, since ~50% of men and ~10% women who carry them are affected. Thus additional modifying factors must exist. In this study, we use next generation sequencing to investigate the role of whole mtDNA variation in male Polish patients with LHON and m.11778G > A, the most frequent LHON mutation. We present a possible association between mtDNA haplogroup K and variants in its background, a combination of m.3480A > G, m.9055G > A, m.11299 T > C and m.14167C > T, and LHON mutation. These variants may have a negative effect on m.11778G > A increasing its penetrance and the risk of LHON in the Polish population. Surprisingly, we did not observe associations previously reported for m.11778G > A and LHON in European populations, particularly for haplogroup J as a risk factor, implying that mtDNA variation is much more complex. Our results indicate possible contribution of novel combination of mtDNA genetic factors to the LHON phenotype.

scholarly journals Single-Nucleotide Polymorphisms in MICA and MICB Genes Could Play a Role in the Outcome in AML Patients after HSCT

2021 ◽  
Vol 10 (20) ◽  
pp. 4636
Author(s):  
Alena Machuldova ◽  
Lucie Houdova ◽  
Katerina Kratochvilova ◽  
Martin Leba ◽  
Pavel Jindra ◽  
...  
Keyword(s):  
Nk Cells ◽  
Myeloid Leukemia ◽  
Point Mutations ◽  
Single Amino Acid ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Negative Effect

NKG2D and its ligands, MICA and MICB, are known as the key regulators of NK cells. NK cells are the first reconstituted cells after the allogeneic hematopoietic stem cell transplantation (HSCT); therefore, it is crucial to understand their role in HSCT outcome. In the presented study, we investigated the single amino acid changes across the exons 2–4 of MICA and MICB genes, and point mutations within the NKG2D gene, which defines the type of NKG2D haploblock (HNK/LNK) in the donors (n = 124), as well as in patients with acute myeloid leukemia (n = 78). In our cohort, we found that graft from a donor with at least one MICA allele containing glycine at position 14 (MICA-14Gly) is significantly associated with deterioration of a patient’s overall survival (OS) (p < 0.05). We also observed a negative effect of MICB-58 (Lys → Glu) polymorphism on relapse-free survival (RFS), although it was not statistically significant in multivariate analysis (p = 0.069). To our knowledge, this is the first work describing the role of MICA-14 and MICB-58 polymorphisms on HSCT outcome.

scholarly journals Cdc42 Regulation of Kinase Activity and Signaling by the Yeast p21-Activated Kinase Ste20

2002 ◽  
Vol 22 (9) ◽  
pp. 2939-2951 ◽  
Author(s):  
Rachel E. Lamson ◽  
Matthew J. Winters ◽  
Peter M. Pryciak
Keyword(s):  
Kinase Activity ◽  
Active Form ◽  
Point Mutations ◽  
Pheromone Response ◽  
Pheromone Signaling ◽  
Negative Effect ◽  
Kinase Cascade ◽  
P21 Activated Kinase

ABSTRACT The Saccharomyces cerevisiae kinase Ste20 is a member of the p21-activated kinase (PAK) family with several functions, including pheromone-responsive signal transduction. While PAKs are usually activated by small G proteins and Ste20 binds Cdc42, the role of Cdc42-Ste20 binding has been controversial, largely because Ste20 lacking its entire Cdc42-binding (CRIB) domain retains kinase activity and pheromone response. Here we show that, unlike CRIB deletion, point mutations in the Ste20 CRIB domain that disrupt Cdc42 binding also disrupt pheromone signaling. We also found that Ste20 kinase activity is stimulated by GTP-bound Cdc42 in vivo and this effect is blocked by the CRIB point mutations. Moreover, the Ste20 CRIB and kinase domains bind each other, and mutations that disrupt this interaction cause hyperactive kinase activity and bypass the requirement for Cdc42 binding. These observations demonstrate that the Ste20 CRIB domain is autoinhibitory and that this negative effect is antagonized by Cdc42 to promote Ste20 kinase activity and signaling. Parallel results were observed for filamentation pathway signaling, suggesting that the requirement for Cdc42-Ste20 interaction is not qualitatively different between the mating and filamentation pathways. While necessary for pheromone signaling, the role of the Cdc42-Ste20 interaction does not require regulation by pheromone or the pheromone-activated Gβγ complex, because the CRIB point mutations also disrupt signaling by activated forms of the kinase cascade scaffold protein Ste5. In total, our observations indicate that Cdc42 converts Ste20 to an active form, while pathway stimuli regulate the ability of this active Ste20 to trigger signaling through a particular pathway.

Social Motives Predict Loneliness During a Developmental Transition

2017 ◽  
Vol 76 (4) ◽  
pp. 145-153 ◽  
Author(s):  
Jana Nikitin ◽  
Alexandra M. Freund
Keyword(s):  
Social Relationships ◽  
Well Being ◽  
Social Avoidance ◽  
Social Approach ◽  
Social Motives ◽  
Developmental Transitions ◽  
Avoidance Motivation ◽  
Negative Effect ◽  
Low Levels

Abstract. Establishing new social relationships is important for mastering developmental transitions in young adulthood. In a 2-year longitudinal study with four measurement occasions (T1: n = 245, T2: n = 96, T3: n = 103, T4: n = 85), we investigated the role of social motives in college students’ mastery of the transition of moving out of the parental home, using loneliness as an indicator of poor adjustment to the transition. Students with strong social approach motivation reported stable and low levels of loneliness. In contrast, students with strong social avoidance motivation reported high levels of loneliness. However, this effect dissipated relatively quickly as most of the young adults adapted to the transition over a period of several weeks. The present study also provides evidence for an interaction between social approach and social avoidance motives: Social approach motives buffered the negative effect on social well-being of social avoidance motives. These results illustrate the importance of social approach and social avoidance motives and their interplay during developmental transitions.

THE NOTHING THAT REALLY IS!

2016 ◽  
Vol 12 (1) ◽  
pp. 4172-4177
Author(s):  
Abdul Malek
Keyword(s):  
Quantum Dynamics ◽  
Theoretical Physics ◽  
Historical Evolution ◽  
Proper Understanding ◽  
Physical Universe ◽  
Wave Particle Duality ◽  
Negative Effect ◽  
Materialist Interpretation

The denial of the existence of contradiction is at the root of all idealism in epistemology and the cause for alienations.  This alienation has become a hindrance for the understanding of the nature and the historical evolution mathematics itself and its role as an instrument in the enquiry of the physical universe (1). A dialectical materialist approach incorporating  the role of the contradiction of the unity of the opposites, chance and necessity etc., can provide a proper understanding of the historical evolution of mathematics and  may ameliorate  the negative effect of the alienation in modern theoretical physics and cosmology. The dialectical view also offers a more plausible materialist interpretation of the bewildering wave-particle duality in quantum dynamics (2).

Peran Badan Pengendalian Dampak Lingkungan dalam Pengendalian Dampak Pencemaran Kegiatan Industri di Kota Batam tahun 2011-2014

2015 ◽  
Vol 14 (1) ◽  
pp. 20
Author(s):  
Wan Asrida ◽  
Dian Arival Aryadana
Keyword(s):  
Environmental Impact ◽  
Environmental Pollution ◽  
Pollution Control ◽  
Control Agency ◽  
Accurate Method ◽  
Industrial Activity ◽  
Research Issues ◽  
Negative Effect ◽  
Research Show

This research is intended to find out the role of the regional environmental impact Control Agency of Batam City against the environmental problems that occur in industrial areas namely, Batam city, concerning sustainable development based upon the environment, the activities of the industry now aims to build an economic sector but has a negative effect that is the pollution of the environment. In this case in Batam city frequent occurrence of environmental pollution caused by industrial activity namely with disposal of waste which are not in place. This research is focused on environmental impact Control Agency area of Batam city authorities in the control of the environment . With the outline of the research issues namely how environmental impact Control Agency the role of the Regions in the control of pollution of the environment against industrial activity in Batam city in 2011-2014 and the factors restricting the role of the regional environmental impact Control Agency in controlling environmental pollution in Batam city in 2011-2014.Type of this research is a descriptive i.e. researchers provide a description and overview of the phenomenon or social symptoms examined by independent variables described in a systematic and accurate. Method of data collection is done by means of interviews and the documentation.The results of this research show that the role of environmental impact Control Agency area of Batam city in pollution control against industrial activity carried out according to its function but have not run well in accordance with the goals and targets that have been set. This is not in accordance with the duties and functions of the regional environmental impact Control Agency of Batam city, resulting in less the maximum role of Bapedalda itself in controlling pollution that occurred in Batam city. So it should be should be able to stake Bapedalda holder which is professional in the discharge of pollution control and must be capable of tackling the obstacles faced.

Role of key point Mutations in Receptor Binding Domain of SARS-CoV-2 Spike Glycoprotein

2020 ◽  
Vol 20 ◽  
Author(s):  
Bipin Singh
Keyword(s):  
Receptor Binding ◽  
Point Mutations ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Angiotensin Converting Enzyme 2 ◽  
Recent Outbreak ◽  
Novel Coronavirus ◽  
Genomic Similarity

: The recent outbreak of novel coronavirus (SARS-CoV-2 or 2019-nCoV) and its worldwide spread is posing one of the major threats to human health and the world economy. It has been suggested that SARS-CoV-2 is similar to SARSCoV based on the comparison of the genome sequence. Despite the genomic similarity between SARS-CoV-2 and SARSCoV, the spike glycoprotein and receptor binding domain in SARS-CoV-2 shows the considerable difference compared to SARS-CoV, due to the presence of several point mutations. The analysis of receptor binding domain (RBD) from recently published 3D structures of spike glycoprotein of SARS-CoV-2 (Yan, R., et al. (2020); Wrapp, D., et al. (2020); Walls, A. C., et al. (2020)) highlights the contribution of a few key point mutations in RBD of spike glycoprotein and molecular basis of its efficient binding with human angiotensin-converting enzyme 2 (ACE2).

The path of support-to-sales: mediating role of seller collaborative information exchange in social commerce

2020 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Li Chen ◽  
Fengxia Zhu ◽  
Murali Mantrala
Keyword(s):  
Information Exchange ◽  
Instrumental Support ◽  
Trade Volume ◽  
Social Commerce ◽  
Content Type ◽  
Mediating Role ◽  
The Social ◽  
Source Data ◽  
Negative Effect

Purpose This paper aims to systematically investigate the direct and indirect effects of four types of support – peer instrumental support, peer emotional support, platform business support and platform communication support – on seller trade volume in social commerce. It also aims to uncover the path of support-to-sales of the seller from a platform perspective and provides a more complete picture of the social commerce phenomenon. Design/methodology/approach This paper uses multi-source data including primary survey data and secondary data on trade volume to test the hypotheses. PROCESS mediation model is used to analyze the multi-source data set. Findings This study finds that the positive effects of peer instrumental support, platform business support and platform communication support on seller trade volume are fully mediated by seller collaborative information exchange. Also, peer emotional support has a significant negative effect on seller trade volume and collaborative information exchange can serve as a buffer to mitigate the negative effect. Research limitations/implications The authors provide new insights into what types of support are or are not conducive to improving transaction volume of individual sellers and highlight the mediating role of seller information exchange in this value generation process in social commerce. These findings advance current knowledge of how seller interactions increase value in social commerce. The chosen research setting may limit the generalizability of the findings of this study. Practical implications This paper offers valuable implications for social commerce platforms on how to better serve their sellers to achieve high growth. Specifically, the findings suggest that platforms should encourage instrumental support and information exchange among peer sellers. In addition, platforms should expand seller support from a single-focus on sellers’ business to a dual-focus on both sellers’ business and socialization in social commerce. Originality/value This paper fulfills an identified need to study how sellers can better derive value from the social interactions and how social commerce platforms can effectively influence transactions, support sales and serve as a selling platform.

scholarly journals Effects of Vector Maturation Time on the Dynamics of Cassava Mosaic Disease

2021 ◽  
Vol 83 (8) ◽  
Author(s):  
F. Al Basir ◽  
Y. N. Kyrychko ◽  
K. B. Blyuss ◽  
S. Ray
Keyword(s):  
Time Delay ◽  
Plant Density ◽  
Plant Viruses ◽  
Mosaic Disease ◽  
Plant Diseases ◽  
Cassava Mosaic Disease ◽  
Maturation Time ◽  
Negative Effect ◽  
Dynamical Regimes

AbstractMany plant diseases are caused by plant viruses that are often transmitted to plants by vectors. For instance, the cassava mosaic disease, which is spread by whiteflies, has a significant negative effect on plant growth and development. Since only mature whiteflies can contribute to the spread of the cassava mosaic virus, and the maturation time is non-negligible compared to whitefly lifetime, it is important to consider the effects this maturation time can have on the dynamics. In this paper, we propose a mathematical model for dynamics of cassava mosaic disease that includes immature and mature vectors and explicitly includes a time delay representing vector maturation time. A special feature of our plant epidemic model is that vector recruitment is negatively related to the delayed ratio between vector density and plant density. We identify conditions of biological feasibility and stability of different steady states in terms of system parameters and the time delay. Numerical stability analyses and simulations are performed to explore the role of various parameters, and to illustrate the behaviour of the model in different dynamical regimes. We show that the maturation delay may stabilise epidemiological dynamics that would otherwise be cyclic.

scholarly journals PATH-17. NOVEL DUAL HISTONE 3 K27M AND G34R POINT MUTATIONS IN A MIDLINE GLIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii167-ii167
Author(s):  
Peter Pan ◽  
Tejus Bale ◽  
Alexandra Miller ◽  
Marc Ladanyi ◽  
Marc Rosenblum ◽  
...  
Keyword(s):  
Point Mutations ◽  
Histone 3 ◽  
First Case ◽  
Microvascular Proliferation ◽  
Motor Neuron Facial Nerve ◽  
Methylguanine Methyltransferase ◽  
Mitotic Figures ◽  
In Cis ◽  
Generation Sequencing ◽  
Diffuse Midline Glioma

Abstract BACKGROUND Histone H3 alterations due to mutations on H3F3A and HIST1H3B genes, have in recent years been associated with distinct entities and tumor locations within the context of infiltrative gliomas. H3K27M is associated with a midline location and is included in the WHO 2016 as the diffuse midline glioma H3K27M-mutant, a specific diagnostic entity. H3G34R, thought to be a mutually exclusive alteration, is less common but has been associated with a cerebral hemispheric location. We report the first case to our knowledge with both of these alterations in the same tumor. METHODS Clinical and pathologic records of the patient were reviewed and presented. RESULTS A 39-year-old man presented with acute right face, arm, and leg numbness and mild weakness; examination was notable for right lower motor neuron facial nerve palsy and numbness, along with numbness and subtle slowing of rapid alternating movements in the left arm and leg. A non-enhancing left thalamic mass was identified and stereotactically biopsied. Infiltrative glial neoplasm with moderately-increased cellularity was seen, with ovoid cells, enlarged nuclei, apoptotic bodies, and mitotic figures. No necrosis or microvascular proliferation seen. Immunostain was positive for H3K27M. O6-methylguanine-methyltransferase (MGMT) promoter was not methylated. Next-generation sequencing showed dual in cis H3 point mutations in K27M (HIST1H3B c.83A &gt;T) and G34R (HIST1H3B c.103G &gt;C). Additional alterations were noted in NF1, PIK3CA, ATRX, FGFR3, and NSD1. Isocitrate dehydrogenase (IDH1/2) mutations were not identified. CONCLUSION This case of a young man with a midline glioma is novel for carrying both H3K27M and H3G34R alterations and indicates these alterations are not mutually exclusive. The interaction seen here suggests H3K27M dominance for a midline phenotype.

scholarly journals Drought and Salinity in Citriculture: Optimal Practices to Alleviate Salinity and Water Stress

Agronomy ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1283
Author(s):  
Vasileios Ziogas ◽  
Georgia Tanou ◽  
Giasemi Morianou ◽  
Nektarios Kourgialas
Keyword(s):  
Agricultural Sector ◽  
Review Paper ◽  
Cell Metabolism ◽  
High Water ◽  
Crop Productivity ◽  
Fruit Tree ◽  
Key Factors ◽  
Negative Effect

Among the various abiotic stresses, drought is the major factor limiting crop productivity worldwide. Citrus has been recognized as a fruit tree crop group of great importance to the global agricultural sector since there are 140 citrus-producing countries worldwide. The majority of citrus-producing areas are subjected to dry and hot summer weather, limited availability of water resources with parallel low-quality irrigation water due to increased salinity regimes. Citrus trees are generally classified as “salt-intolerant” with high water needs, especially during summer. Water scarcity negatively affects plant growth and impairs cell metabolism, affecting the overall tree growth and the quality of produced fruit. Key factors that overall attempt to sustain and withstand the negative effect of salinity and drought stress are the extensive use of rootstocks in citriculture as well as the appropriate agronomical and irrigation practices applied. This review paper emphasizes and summarizes the crucial role of the above factors in the sustainability of citriculture.

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