Modulation of Lipid Kinase PI4KIIα Activity and Lipid Raft Association of Presenilin 1 Underlies γ-Secretase Inhibition by Ginsenoside (20<i>S</i>)-Rg3

Kang, Min Suk,Baek, Seung-Hoon,Chun, Yoon Sun,Moore, A. Zenobia,Landman, Natalie,Berman, Diego,Yang, Hyun Ok,Morishima-Kawashima, Maho,Osawa, Satoko,Funamoto, Satoru,Ihara, Yasuo,Di Paolo, Gilbert,Par American Society for Biochemistry and Molecular Bi 2013 The Journal of biological chemistry Vol.288 No.29

<P>Amyloid β-peptide (Aβ) pathology is an invariant feature of Alzheimer disease, preceding any detectable clinical symptoms by more than a decade. To this end, we seek to identify agents that can reduce Aβ levels in the brain via novel mechanisms. We found that (20<I>S</I>)-Rg3, a triterpene natural compound known as ginsenoside, reduced Aβ levels in cultured primary neurons and in the brains of a mouse model of Alzheimer disease. The (20<I>S</I>)-Rg3 treatment induced a decrease in the association of presenilin 1 (PS1) fragments with lipid rafts where catalytic components of the γ-secretase complex are enriched. The Aβ-lowering activity of (20<I>S</I>)-Rg3 directly correlated with increased activity of phosphatidylinositol 4-kinase IIα (PI4KIIα), a lipid kinase that mediates the rate-limiting step in phosphatidylinositol 4,5-bisphosphate synthesis. PI4KIIα overexpression recapitulated the effects of (20<I>S</I>)-Rg3, whereas reduced expression of PI4KIIα abolished the Aβ-reducing activity of (20<I>S</I>)-Rg3 in neurons. Our results substantiate an important role for PI4KIIα and phosphoinositide modulation in γ-secretase activity and Aβ biogenesis.</P>

Genome-wide identification and functional prediction of silicon (Si) transporters in poplar (Populus trichocarpa)

Hassan Md Mahmudul,Martin Samir,Feng Kai,Yates Timothy B.,Yuan Guoliang,Martin Madhavi Z.,Martin Stanton,Muchero Wellington,Griffiths Natalie A.,Weston David J.,Yang Xiaohan 한국식물생명공학회 2023 Plant biotechnology reports Vol.17 No.2

Silicon (Si) enhances plant tolerance to various biotic and abiotic stressors such as salinity, drought, and heat. In addition, Si can be biomineralized within plants to form organic carbon-containing phytoliths that can have ecosystem-level consequences by contributing to long-term carbon sequestration. Si is taken up and transported in plants via different transporter proteins such as influx transporters (e.g., Lsi1, Lsi6) and efflux transporters (e.g., Lsi2). Additionally, the imported Si can be deposited in plant leaves via silicification process using the Siliplant 1 (e.g., Slp1) protein. Functional homologs of these proteins have been reported in different food crops. Here, we performed a genome-wide analysis to identify different Si transporters and Slp1 homologs in the bioenergy crop poplar (Populus trichocarpa Torr. and A. Gray ex W. Hook). We identified one channel-type Si influx transporter (PtLsi1; Potri.017G083300), one Si efflux transporter (PtLsi2; Potri.012G144000) and two proteins like Slp1 (PtSlp1a; Potri.004G168600 and PtSlp1b; Potri.009G129900) in the P. trichocarpa genome. We found a unique sequence (KPKPPVFKPPPVPI) in PtSlp1a which is repeated six times. Repeated presence of this sequence in PtSlp1a indicates that this protein might be important for silicification processes in P. trichocarpa. The mutation profiles of different Si transporters in a P. trichocarpa genome-wide association study population identified significant and impactful mutations in Potri.004G168600 and Potri.009G129900. Using a publically accessible database (http://bar.utoronto.ca/eplant_poplar/), digital expression analysis of the putative Si transporters in P. trichocarpa found low to moderate expression in the anticipated tissues, such as roots and leaves. Subcellular localization analysis found that PtLsi1/PtLsi2 are localized in the plasma membrane, whereas PtSlp1a/PtSlp1b are found in the extracellular spaces. Protein–Protein interaction analysis of PtLsi1/PtLsi2 identified Delta-1-pyrroline-5-carboxylate synthase (P5CS) as one of the main interacting partners of PtLsi2, which plays a key role in proline biosynthesis. Proline is a well-known participant in biotic and abiotic stress tolerance in plants. These findings will reinforce future efforts to modify Si accumulation for enhancing plant stress tolerance and carbon sequestration in poplar.

Formation of the Digital Generation in a Distance Learning Environment

Nataliіa, Levchenko,Nataliia, Sukhostavets,Lesia, Zelman,Alla, Kulichenko,Kseniia, Balabanova International Journal of Computer ScienceNetwork S 2022 International journal of computer science and netw Vol.22 No.5

This article is devoted to the study of the process of formation of the digital generation in a distance learning environment. With the introduction of quarantine due to the spread of COVID-19, opponents of digital technologies were forced to turn to relevant resources, while supporters identified new opportunities for the development of didactics and education in general. The irreversibility of the former educational reality became apparent and only the scale of the vision of potential change by interested and disinterested groups differed. Using a comprehensive approach, the authors consider the issues related to the direct and indirect impact of distance learning on children and young people born after the beginning of the XXI century. The article reveals the prerequisites and implications of distance education for the interaction of participants in the educational process. IC technologies during the educational process in the primary grades, in addition to identifying the student's learning deficit, should provide the transmission of non-verbal signals, which are important for children of this age. At the same time in the secondary school IR-technologies are designed to replace frontal learning during the assimilation of knowledge and at the same time not to worsen the quality of the educational process. Formation of students in the HEI takes place in the political science format, constant discussion of problem situations, so the task of introducing IC technology in this process is the accurate transfer of the content of the discussions. Individualization and autonomization of the educational process, its dependence on the results of the choice of educational content, and the use of pedagogical management tools change the philosophy of education for children and youth. The authors conclude that the formation of a digital generation, characterized by an increased level of digital literacy of children and youth, the possession of a certain level of digital capacity requires the use of strategies aimed at optimizing the learning process in a digital educational environment.

Information Technologies in The Process of Teaching Foreign Languages in Higher Educational Institutions

Fabian, Myroslava,Shavlovska, Tetiana,Shpenyk, Silviia,Khanykina, Nataliіa,Tyshchenko, Oleh,Lebedynets, Hanna International Journal of Computer ScienceNetwork S 2021 International journal of computer science and netw Vol.21 No.3

An anthological analysis of known literature and historical sources is carried out in the work. It was found that the development of foreign language training of future professionals was influenced by a number of factors: socio-economic (focus on the needs of the labor market, integration into the international space, scientific and technological progress); educational (updating legal documents in the field of education, standardization of educational content, development of methods of professional development of a specialist). The historical period is analyzed and the following stages are determined: ideological (realization of ideological imperative in language and professional training of future specialists; educational-methodical (preparation according to unified curricula, reading and translation as a leading type of speech activity); integration (integration of foreign language teaching and multicultural education)), methodological (use of traditional verbal methods, standardized textbooks). Thus, the research conducted in the article indicates the periods (stages) of formation, functioning and development of foreign language education.

Application Of Innovative Technologies In Higher Education Institutions Of Ukraine: Forms And Methods

Dovgal, Olena,Havrylova, Olena,Potryvaieva, Natalia,Tolstova, Natalia,Ostapchuk, Taras,Onyshchenko, Nataliіa International Journal of Computer ScienceNetwork S 2021 International journal of computer science and netw Vol.21 No.5

In the course of this article, the concept of "innovation" was considered and analyzed, which is considered not only as a subject, something new, but also as a process. The process of introducing something new into life, and in our case, into the educational process. Innovative educational technologies are varied and plentiful. In this article, the most commonly used. Among them: the use of ICT, game techniques, the portfolio method, personality-oriented, information support of the learning process, educational and health-saving technologies, and others.

Versailles Project on Advanced Materials and Standards Interlaboratory Study on Measuring the Thickness and Chemistry of Nanoparticle Coatings Using XPS and LEIS

Belsey, Natalie A.,Cant, David J. H.,Minelli, Caterina,Araujo, Joyce R.,Bock, Bernd,Brü,ner, Philipp,Castner, David G.,Ceccone, Giacomo,Counsell, Jonathan D. P.,Dietrich, Paul M.,Engelhard, Mark American Chemical Society 2016 The Journal of Physical Chemistry Part C Vol.120 No.42

<P>We report the results of a Versailles Project on Advanced Materials and Standards (VAMAS) interlaboratory study on the measurement of the shell thickness and chemistry of nanoparticle coatings. Peptide-coated gold particles were supplied to laboratories in two forms: a colloidal suspension in pure water and particles dried onto a silicon wafer. Participants prepared and analyzed these samples using either X-ray photoelectron spectroscopy (XPS) or low energy ion scattering (LEIS). Careful data analysis revealed some significant sources of discrepancy, particularly for XPS. Degradation during transportation, storage, or sample preparation resulted in a variability in thickness of 53%. The calculation method chosen by XPS participants contributed a variability of 67%. However, variability of 12% was achieved for the samples deposited using a single method and by choosing photoelectron peaks that were not adversely affected by instrumental transmission effects. The study identified a need for more consistency in instrumental transmission functions and relative sensitivity factors since this contributed a variability of 33%. The results from the LEIS participants were more consistent, with variability of less than 10% in thickness, and this is mostly due to a common method of data analysis. The calculation was performed using a model developed for uniform, flat films, and some participants employed a correction factor to account for the sample geometry, which appears warranted based upon a simulation of LEIS data from one of the participants and comparison to the XPS results.</P>

3D shape analysis of the brain's third ventricle using a midplane encoded symmetric template model

Kim, Jaeil,Valdé,s Herná,ndez, Maria del C.,Royle, Natalie A.,Maniega, Susana Muñ,oz,Aribisala, Benjamin S.,Gow, Alan J.,Bastin, Mark E.,Deary, Ian J.,Wardlaw, Joanna M.,Park, Jinah Elsevier Scientific Publishers 2016 Computer Methods and Programs in Biomedicine Vol.129 No.-

<▼1><P><B>Highlights</B></P><P>•<P>Present a model-based approach to investigate the morphology of the third ventricle.</P>•<P>Assess the regional deformations in relation to the atrophy of surrounding structures.</P>•<P>Use a symmetric template model with the midplane definition for unbiased analysis.</P>•<P>Achieve a robust surface modeling using a progressive surface deformation.</P>•<P>Validate the method on a healthy aging sample with different clinical variables.</P></P></▼1><▼2><P><B>Background</B></P><P>Structural changes of the brain's third ventricle have been acknowledged as an indicative measure of the brain atrophy progression in neurodegenerative and endocrinal diseases. To investigate the ventricular enlargement in relation to the atrophy of the surrounding structures, shape analysis is a promising approach. However, there are hurdles in modeling the third ventricle shape. First, it has topological variations across individuals due to the inter-thalamic adhesion. In addition, as an interhemispheric structure, it needs to be aligned to the midsagittal plane to assess its asymmetric and regional deformation.</P><P><B>Method</B></P><P>To address these issues, we propose a model-based shape assessment. Our template model of the third ventricle consists of a midplane and a symmetric mesh of generic shape. By mapping the template's midplane to the individuals’ brain midsagittal plane, we align the symmetric mesh on the midline of the brain before quantifying the third ventricle shape. To build the vertex-wise correspondence between the individual third ventricle and the template mesh, we employ a minimal-distortion surface deformation framework. In addition, to account for topological variations, we implement geometric constraints guiding the template mesh to have zero width where the inter-thalamic adhesion passes through, preventing vertices crossing between left and right walls of the third ventricle. The individual shapes are compared using a vertex-wise deformity from the symmetric template.</P><P><B>Results</B></P><P>Experiments on imaging and demographic data from a study of aging showed that our model was sensitive in assessing morphological differences between individuals in relation to brain volume (i.e. proxy for general brain atrophy), gender and the fluid intelligence at age 72. It also revealed that the proposed method can detect the regional and asymmetrical deformation unlike the conventional measures: volume (median 1.95 ml, IQR 0.96 ml) and width of the third ventricle. Similarity measures between binary masks and the shape model showed that the latter reconstructed shape details with high accuracy (Dice coefficient ≥0.9, mean distance 0.5 mm and Hausdorff distance 2.7 mm).</P><P><B>Conclusions</B></P><P>We have demonstrated that our approach is suitable to morphometrical analyses of the third ventricle, providing high accuracy and inter-subject consistency in the shape quantification. This shape modeling method with geometric constraints based on anatomical landmarks could be extended to other brain structures which require a consistent measurement basis in the morphometry.</P></▼2>

Is There a "Trial Effect" on Outcome of Patients with Metastatic Renal Cell Carcinoma Treated with Sunitinib?

Daniel Keizman,Keren Rouvinov,Avishay Sella,Maya Gottfried,Natalie Maimon,Jenny J. Kim,Mario A. Eisenberger,Victoria Sinibaldi,Avivit Peer,Michael A. Carducci,Wilmosh Mermershtain,Raya Leibowitz-amit 대한암학회 2016 Cancer Research and Treatment Vol.48 No.1

Purpose Studies suggested the existence of a ‘trial effect,’ in which for a given treatment, participa- tion in a clinical trial is associated with a better outcome. Sunitinib is a standard treatment for metastatic renal cell carcinoma (mRCC). We aimed to study the effect of clinical trial participation on the outcome of mRCC patients treated with sunitinib, which at present, is poorly defined. Materials and Methods The records of mRCC patients treated with sunitinib between 2004-2013 in 7 centers across 2 countries were reviewed. We compared the response rate (RR), progression free survival (PFS), and overall survival (OS), between clinical trial participants (n=49) and a matched cohort of non-participants (n=49) who received standard therapy. Each clinical trial participant was individually matched with a non-participant by clinicopathologic factors. PFS and OS were determined by Cox regression. Results The groups were matched by age (median, 64), sex (male, 67%), Heng risk (favorable, 25%; intermediate, 59%; poor, 16%), prior nephrectomy (92%), RCC histology (clear cell 86%), pre-treatment neutrophil to lymphocyte ratio (> 3 in 55%, n=27), sunitinib induced hyper- tension (45%), and sunitinib dose reduction/treatment interruption (41%). In clinical trial participants versus non-participants, RR was partial response/stable disease 80% (n=39) versus 74% (n=36), and progressive disease 20% (n=10) versus 26% (n=13) (p=0.63; odds ratio, 1.2). The median PFS was 10 versus 11 months (hazard ratio [HR], 0.96; p=0.84), and the median OS 23 versus 24 months (HR, 0.97; p=0.89). Conclusion In mRCC patients treated with sunitinib, the outcome of clinical trial participants was similar to that of non-participants who received standard therapy.

Synergistic Phytochemicals Fail to Protect Against Ovariectomy Induced Bone Loss in Rats

Suresh Ambati,Colette N. Miller,Erica F. Bass,Natalie M. Hohos,Diane L. Hartzell,Emily W. Kelso,Emily R. Trunnell,양정예,Mary Anne Della-Fera,Clifton A. Baile,Srujana Rayalam 한국식품영양과학회 2018 Journal of medicinal food Vol.21 No.10

Menopause induces a loss of bone as a result of estrogen deficiency. Despite pharmaceutical options for the treatment of osteopenia and osteoporosis, many aging women use dietary supplements with estrogenic activity to prevent bone loss and other menopausal-related symptoms. Such supplements are yet to be tested for efficacy against a Food and Drug Administration (FDA) approved medication for menopausal bone loss such as zoledronic acid (ZA). The postmenopausal rat model was used to investigate the efficacy of various synergistic phytochemical blends mixed into the diet for 16 weeks. Retired-breeder, Fischer 344 rats were randomly assigned to sham or ovariectomy surgery and 4 treatment groups: ZA; genistein supplementation; and a low dose and high dose blend of genistein, resveratrol, and quercetin. Ovariectomy resulted in a loss of both trabecular and cortical bone which was prevented with ZA. The phytochemical blends tested were unable to reverse these losses. Despite the lack of effectiveness in preventing bone loss, a significant dose–response trend was observed in the phytochemical-rich diets in bone adipocyte number compared to ovariectomized control rats. Data from this study indicate that estrogenic phytochemicals are not as efficacious as ZA in preventing menopausal-related bone loss but may have beneficial effects on bone marrow adiposity in rats.

Hippocampal morphology and cognitive functions in community-dwelling older people: the Lothian Birth Cohort 1936

Valdé,s Herná,ndez, Maria del Carmen,Cox, Simon R.,Kim, Jaeil,Royle, Natalie A.,Muñ,oz Maniega, Susana,Gow, Alan J.,Anblagan, Devasuda,Bastin, Mark E.,Park, Jinah,Starr, John M.,Ward Elsevier 2017 NEUROBIOLOGY OF AGING Vol.52 No.-

<P>Structural measures of the hippocampus have been linked to a variety of memory processes and also to broader cognitive abilities. Gross volumetry has been widely used, yet the hippocampus has a complex formation, comprising distinct subfields which may be differentially sensitive to the deleterious effects of age, and to different aspects of cognitive performance. However, a comprehensive analysis of multidomain cognitive associations with hippocampal deformations among a large group of cognitively normal older adults is currently lacking. In 654 participants of the Lothian Birth Cohort 1936 (mean age = 72.5, SD = 0.71 years), we examined associations between the morphology of the hippocampus and a variety of memory tests (spatial span, letter-number sequencing, verbal recall, and digit backwards), as well as broader cognitive domains (latent measures of speed, fluid intelligence, and memory). Following correction for age, sex, and vascular risk factors, analysis of memory subtests revealed that only right hippocampal associations in relation to spatial memory survived type 1 error correction in subiculum and in CA1 at the head (<I>β</I> = 0.201, <I>p</I> = 5.843 × 10<SUP>−4</SUP>, outward), and in the ventral tail section of CA1 (<I>β</I> = −0.272, <I>p</I> = 1.347 × 10<SUP>−5</SUP>, inward). With respect to latent measures of cognitive domains, only deformations associated with processing speed survived type 1 error correction in bilateral subiculum (<I>β</I><SUB><I>absolute</I></SUB> ≤ 0.247, <I>p</I> < 1.369 × 10<SUP>−4</SUP>, outward), bilaterally in the ventral tail section of CA1 (<I>β</I><SUB><I>absolute</I></SUB> ≤ 0.242, <I>p</I> < 3.451 × 10<SUP>−6</SUP>, inward), and a cluster at the left anterior-to-dorsal region of the head (<I>β</I> = 0.199, <I>p</I> = 5.220 × 10<SUP>−6</SUP>, outward). Overall, our results indicate that a complex pattern of both inward and outward hippocampal deformations are associated with better processing speed and spatial memory in older age, suggesting that complex shape-based hippocampal analyses may provide valuable information beyond gross volumetry.</P>