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التدفق الهادئ لنهر أونا
يوثق الكاتب البوسني فاروق شهيتش في روايته \"التدفق الهادئ لنهر أونا\" الحرب الأهلية في البوسنة في عقد التسعينات من القرن الماضي وما رافقها من انتهاكات بحق البوسنيين ومن أولى سطور الكتاب، يقول الكاتب إنه \"لا مجال هنا للإنسانية وللنهضة، هذا ما اعتقدناه حينه\" وكان لانهيار جدار برلين عام 1989، تداعياته على مناطق واسعة من القارة الأوروبية، من ضمنها يوغسلافيا السابقة ذات النظام الفيدرالي الذي وضع أسسه جوزيف بروز تيتو.
Book
The Role of Interruptions in polyQ in the Pathology of SCA1
At least nine dominant neurodegenerative diseases are caused by expansion of CAG repeats in coding regions of specific genes that result in abnormal elongation of polyglutamine (polyQ) tracts in the corresponding gene products. When above a threshold that is specific for each disease the expanded polyQ repeats promote protein aggregation, misfolding and neuronal cell death. The length of the polyQ tract inversely correlates with the age at disease onset. It has been observed that interruption of the CAG tract by silent (CAA) or missense (CAT) mutations may strongly modulate the effect of the expansion and delay the onset age. We have carried out an extensive study in which we have complemented DNA sequence determination with cellular and biophysical models. By sequencing cloned normal and expanded SCA1 alleles taken from our cohort of ataxia patients we have determined sequence variations not detected by allele sizing and observed for the first time that repeat instability can occur even in the presence of CAG interruptions. We show that histidine interrupted pathogenic alleles occur with relatively high frequency (11%) and that the age at onset inversely correlates linearly with the longer uninterrupted CAG stretch. This could be reproduced in a cellular model to support the hypothesis of a linear behaviour of polyQ. We clarified by in vitro studies the mechanism by which polyQ interruption slows down aggregation. Our study contributes to the understanding of the role of polyQ interruption in the SCA1 phenotype with regards to age at disease onset, prognosis and transmission.
Journal Article
Down-Regulation of the CSLF6 Gene Results in Decreased (1,3;1,4)-β-D-Glucan in Endosperm of Wheat
(1,3;1,4)-β-D-Glucan (β-glucan) accounts for 20% of the total cell walls in the starchy endosperm of wheat (Triticum aestivum) and is an important source of dietary fiber for human nutrition with potential health benefits. Bioinformatic and array analyses of gene expression profiles in developing caryopses identified the CELLULOSE SYNTHASE-LIKE F6 (CSLF6) gene as encoding a putative β-glucan synthase. RNA interference constructs were therefore designed to down-regulate CSLF6 gene expression and expressed in transgenic wheat under the control of a starchy endosperm-specific HMW subunit gene promoter. Analysis of wholemeal flours using an enzyme-based kit and by high-performance anion-exchange chromatography after digestion with lichenase showed decreases in total β-glucan of between 30% and 52% and between 36% and 53%, respectively, in five transgenic lines compared to three control lines. The content of water-extractable β-glucan was also reduced by about 50% in the transgenic lines, and the Mr distribution of the fraction was decreased from an average of 79 to 85 x 10⁴ g/mol in the controls and 36 to 57 x 10⁴ g/mol in the transgenics. Immunolocalization of β-glucan in semithin sections of mature and developing grains confirmed that the impact of the transgene was confined to the starchy endosperm with little or no effect on the aleurone or outer layers of the grain. The results confirm that the CSLF6 gene of wheat encodes a β-glucan synthase and indicate that transgenic manipulation can be used to enhance the health benefits of wheat products.
Journal Article
Coordination to manage dependencies between logistics service providers and shippers
Purpose - Although it has been suggested that shippers' demands regarding environmental practices appear to have an impact on the environmental work of LSPs, limited attention has been given to environmental practices in the relationships between LSPs and shippers. The purpose of this paper is to explore how dependencies between LSPs and shippers can influence the way in which environmental practices are coordinated in the relationships between them. Design/methodology/approach - Four dyadic case studies, each consisting of one LSP and one shipper, provide the empirical basis for this paper. Findings - Two types of dependencies are suggested as having an influence over the coordination of environmental practices in LSP-shipper relationships: dependence between LSPs and shippers as such; and dependence with regard to specific environmental practices. In addition, the environmental ambition of the actors is found to be of relevance when LSPs and shippers coordinate environmental practices between them. Based on these parameters, different coordination mechanisms for environmental practices in LSP-shipper relationships are discussed. Research limitations/implications - The research is limited to four cases in a Swedish context. Additional cases might provide other insights into LSP-shipper relationships and thereby lead to modifications of the proposed conceptual framework. Practical implications - The results can help both LSPs and shippers improve their work with environmental practices through the use of the appropriate coordination mechanisms in their inter-organisational relationships. Originality/value - Contrary to previous research, which mainly takes one party's perspective, this paper takes a dyadic approach and thereby adds valuable knowledge to the inter-organisational aspects of LSPs' environmental work.
Journal Article
A Low Temperature Limit for Life on Earth
There is no generally accepted value for the lower temperature limit for life on Earth. We present empirical evidence that free-living microbial cells cooling in the presence of external ice will undergo freeze-induced desiccation and a glass transition (vitrification) at a temperature between -10°C and -26°C. In contrast to intracellular freezing, vitrification does not result in death and cells may survive very low temperatures once vitrified. The high internal viscosity following vitrification means that diffusion of oxygen and metabolites is slowed to such an extent that cellular metabolism ceases. The temperature range for intracellular vitrification makes this a process of fundamental ecological significance for free-living microbes. It is only where extracellular ice is not present that cells can continue to metabolise below these temperatures, and water droplets in clouds provide an important example of such a habitat. In multicellular organisms the cells are isolated from ice in the environment, and the major factor dictating how they respond to low temperature is the physical state of the extracellular fluid. Where this fluid freezes, then the cells will dehydrate and vitrify in a manner analogous to free-living microbes. Where the extracellular fluid undercools then cells can continue to metabolise, albeit slowly, to temperatures below the vitrification temperature of free-living microbes. Evidence suggests that these cells do also eventually vitrify, but at lower temperatures that may be below -50°C. Since cells must return to a fluid state to resume metabolism and complete their life cycle, and ice is almost universally present in environments at sub-zero temperatures, we propose that the vitrification temperature represents a general lower thermal limit to life on Earth, though its precise value differs between unicellular (typically above -20°C) and multicellular organisms (typically below -20°C). Few multicellular organisms can, however, complete their life cycle at temperatures below ∼-2°C.
Journal Article
GPCR activation of Ras and PI3K gamma in neutrophils depends on PLC beta 2/ beta 3 and the RasGEF RasGRP4
The molecular mechanisms by which receptors regulate the Ras Binding Domains of the PIP sub(3)-generating, class I PI3Ks remain poorly understood, despite their importance in a range of biological settings, including tumorigenesis, activation of neutrophils by pro-inflammatory mediators, chemotaxis of Dictyostelium and cell growth in Drosophila. We provide evidence that G protein-coupled receptors (GPCRs) can stimulate PLC beta 2/ beta 3 and diacylglycerol-dependent activation of the RasGEF, RasGRP4 in neutrophils. The genetic loss of RasGRP4 phenocopies knock-in of a Ras-insensitive version of PI3K gamma in its effects on PI3K gamma -dependent PIP sub(3) accumulation, PKB activation, chemokinesis and reactive oxygen species (ROS) formation. These results establish a new mechanism by which GPCRs can stimulate Ras, and the broadly important principle that PLCs can control activation of class I PI3Ks.
Journal Article
Benefits of Digital Editing for Japanese Writing Instruction
This study examined the benefits of digital editing for Japanese writing instruction for Indonesian students. The participants of this study were 44 Indonesian university students who had majored in Japanese language and culture for approximately one year. The author of this study taught this course online for seven weeks and asked the participants to email photographs of their essays to him. The teacher first typed the texts of the participants’ essays into Microsoft Word and then he corrected them, adding notes to the students. In this study, students were assigned points for their practice essay and final examination to the maximum of 50 to facilitate the comparison of the scores across individuals. The participants’ practice essays were not scored. The participants were asked to compose on a sheet of 400-character manuscript paper. The teacher deducted one point for each error in grammar, spelling, particle, vocabulary, and conjugation. On average, out of 50 possible points, the participants obtained 37.82 points in the first writing practice and 46.91 points in the final examination. At a 5% level, the scores before and after the instruction through digital editing showed statistically significant differences (p < 0.001, df = 43, t = 15.33). These results show that digital editing using Microsoft Word improves Japanese-language learners’ writing proficiency.
Journal Article
Quantitative Modulation of Polycomb Silencing Underlies Natural Variation in Vernalization
Arabidopsis thaliana accessions have adapted to growth in a wide range of climates. Variation in flowering and alignment of vernalization response with winter length are central to this adaptation. Vernalization involves the epigenetic silencing of the floral repressor FLC via a conserved Polycomb (PRC2) mechanism involving trimethylation of Lys 27 on histone H3 (H3K27me3). We found that variation for response to winter length maps to cis polymorphism within FLC. A rare combination of four polymorphisms localized around the nucleation region of a PHD-Polycomb complex determines a need for longer cold. Chromatin immunoprecipitation experiments indicate that these polymorphisms influence the accumulation of H3K27me3 in Arabidopsis accession Lov-1, both at the nucleation site and over the gene body. Quantitative modulation of chromatin silencing through cis variation may be a general mechanism contributing to evolutionary change.
Journal Article
Gene ontology defines pre-post- hatch energy dynamics in the complexus muscle of broiler chickens
Background
Chicken embryos emerge from their shell by the piercing movement of the hatching muscle. Although considered a key player during hatching, with activity that imposes a substantial metabolic demand, data are still limited. The study provides a bioenergetic and transcriptomic analyses during the pre-post-hatching period.
Methods
Weight and morphology alongside content determination of creatine and glycogen were analysed. Transcriptome identified differentially expressed genes and enriched biological processes associated with hatching muscle development, catabolism, and energy provision. Using gene set enrichment, we followed the dynamics of gene-sets involved in energy pathways of oxidative phosphorylation, protein catabolism, glycolysis/gluconeogenesis, and glycogen metabolism.
Results
Results show several significant findings: (A) Creatine plays a crucial role in the energy metabolism of the hatching muscle, with its concentration remaining stable while glycogen concentration is depleted at hatch and placement. (B) The hatching muscle has the capacity for de-novo creatine synthesis, as indicated by the expression of related genes (AGAT, GAMT). (C) Transcriptome provided insights into genes related to energy pathways under conditions of pre-hatch oxygen and post-hatch glucose limitations (oxidative phosphorylation: NDUF, MT-ND, SDH, UQCR, COX, MT-CO, ATP5, MT-ATP; glycolysis/gluconeogenesis: FBP,G6PC, PFKM; glycogen metabolism: PPP1, PYGL, GYG1). (D) The post-hatch upregulation of protein catabolic processes genes (PSMA, RNF, UBE, FBX), which align with the muscle's weight dynamics, indicates a functional shift from movement during hatching to lifting the head during feeding.
Conclusions
There is a dynamic metabolic switch in the hatching muscle during embryo-to-hatchling transition. When glycogen concentration depletes, energy supply is maintained by creatine and its de-novo synthesis. Understanding the hatching muscle's energy dynamics is crucial, for reducing hatching failures in endangered avian species, and in domesticated chickens.
Journal Article
RNA Interference Suppression of Genes in Glycosyl Transferase Families 43 and 47 in Wheat Starchy Endosperm Causes Large Decreases in Arabinoxylan Content
The cell walls of wheat (Triticum aestivum) starchy endosperm are dominated by arabinoxylan (AX), accounting for 65% to 70% of the polysaccharide content. Genes within two glycosyl transferase (GT) families, GT43 (IRREGULAR XYLEM9 [IRX9] and IRX14) and GT47 (IRX10), have previously been shown to be involved in the synthesis of the xylan backbone in Arabidopsis, and close homologs of these have been implicated in the synthesis of xylan in other species. Here, homologs of IRX10 TaGT47_2 and IRX9 TaGT43_2, which are highly expressed in wheat starchy endosperm cells, were suppressed by RNA interference (RNAi) constructs driven by a starchy endosperm-specific promoter. The total amount of AX was decreased by 40% to 50% and the degree of arabinosylation was increased by 25% to 30% in transgenic lines carrying either of the transgenes. The cell walls of starchy endosperm in sections of grain from TaGT43_2 and TaGT47_2 RNAi transgenics showed decreased immunolabeling for xylan and arabinoxylan epitopes and approximately 50% decreased cell wall thickness compared with controls. The proportion of AX that was water soluble was not significantly affected, but average AX polymer chain length was decreased in both TaGT43_2 and TaGT47_2 RNAi transgenics. However, the long AX chains seen in controls were absent in TaGT43_2 RNAi transgenics but still present in TaGT47_2 RNAi transgenics. The results support an emerging picture of IRX9-like and IRX10-like proteins acting as key components in the xylan synthesis machinery in both dicots and grasses. Since AX is the main component of dietary fiber in wheat foods, the TaGT43_2 and TaGT47_2 genes are of major importance to human nutrition.
Journal Article