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الكوميديا الإلهية
يتناول كتاب (الكوميديا الإلهية) والذي قامه بتأليفه (دانتي أليجييري) في حوالي (942) صفحة من القطع المتوسط موضوع (الشعر الإيطالي) مستعرضا المحتويات التالية : ما برح عمل \"دانتي\" الشعري الأساسي \"الكوميديا الإلهية\" يستنطق الحداثة الشعرية العالمية ويثير في مختلف اللغات الترجمة تلو الأخرى. وقد كتب دانتي نفسه أن عمله قابل لقراءات متعددة، حرفية، ورمزية، شعرية ولاهوتية وأمثولية (أليغورية) إلا أن القراءة الشعرية-الفلسفية هي السائدة اليوم. عن هذا العمل الإبداعي وعن صاحبه يدور الحديث في هذا الكتاب حيث يجد القارئ أولا تصديرا عاما وموجزا يقف فيه فورا على العناصر الأساسية التي ينبغي معرفتها عن العمل وصاحبه ومكانته في الخلق الشعري، وفيمن تكمن. بعد ذلك سيقف القارئ على مدخل نقدي أو دراسي اعتمد فيه الباحث على عدد من القراءات الكبرى الموضوعة في دانتي وكوميدياه الإلهية\" (بورخيس، ريسيه، جيرار، جاكوتيه، إلخ.) وتحمل هذه القراءات أكبر من التعمق والتفصيل. وللقارئ أن يقرأ هذا المدخل قبل قراءة ترجمة الأجزاء الثلاثة بأنشوداتها المائة، أو أن يعود إلى قراءته بعد غوصه في العالم الشعري لدانتي.
Book
Violet-light suppression of thermogenesis by opsin 5 hypothalamic neurons
The opsin family of G-protein-coupled receptors are used as light detectors in animals. Opsin 5 (also known as neuropsin or OPN5) is a highly conserved opsin that is sensitive to visible violet light
1
,
2
. In mice, OPN5 is a known photoreceptor in the retina
3
and skin
4
but is also expressed in the hypothalamic preoptic area (POA)
5
. Here we describe a light-sensing pathway in which POA neurons that express
Opn5
regulate thermogenesis in brown adipose tissue (BAT). We show that
Opn5
is expressed in glutamatergic warm-sensing POA neurons that receive synaptic input from several thermoregulatory nuclei. We further show that
Opn5
POA neurons project to BAT and decrease its activity under chemogenetic stimulation.
Opn5
-null mice show overactive BAT, increased body temperature, and exaggerated thermogenesis when cold-challenged. Moreover, violet photostimulation during cold exposure acutely suppresses BAT temperature in wild-type mice but not in
Opn5
-null mice. Direct measurements of intracellular cAMP ex vivo show that
Opn5
POA neurons increase cAMP when stimulated with violet light. This analysis thus identifies a violet light-sensitive deep brain photoreceptor that normally suppresses BAT thermogenesis.
Mice possess neurons in the preoptic area of the hypothalamus that are sensitive to violet light; these deep brain neurons sense light via OPN5 and regulate adaptive thermogenesis in brown fat.
Journal Article
Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases
Key Points
Equilibrated protein homeostasis (referred to as proteostasis) requires the dynamic coordination of efficient folding of newly synthesized proteins, quality control and degradative mechanisms to reduce the load of unfolded and/or misfolded proteins and thereby prevent abnormal protein aggregation. In response to proteostasis perturbations, the folding and/or degrading capacity of the endoplasmic reticulum (ER) is dynamically adjusted by the induction of a complex signalling network known as the unfolded protein response (UPR).
Most neurodegenerative diseases are considered to be protein misfolding disorders. They have distinct clinical manifestations, but they all involve the accumulation of abnormally folded proteins in the form of small oligomers, aggregates or large-protein inclusions. Disturbance of several aspects of proteostasis contributes to the progression of these neurodegenerative diseases.
Perturbation of ER function or the UPR may be part of the aetiology of several diseases; that is, disease proteins may directly or indirectly perturb the UPR machinery and alter the function of the secretory pathway at different levels, resulting in irreversible alterations in neuronal proteostasis and degeneration.
UPR activation can either enhance or reduce neurodegeneration. UPR adaptive responses or pro-apoptotic programmes are possibly triggered depending on the load of misfolded proteins and the specific UPR signalling mechanisms that are activated.
An ER adaptive response can engage a preconditioning stage by adjusting proteostasis in neurons but can also propagate cell-non-autonomously in the whole organism to maintain global proteostasis and limit ageing. Physiological perturbation of the ER through the engagement of adaptive ER-hormetic mechanisms could be exploited to develop therapeutic strategies that attenuate neurodegeneration.
UPR pathways have physiological functions in different aspects of brain development and function, such as CNS development, learning, memory and hypothalamic functions.
The unfolded protein response (UPR) is a homeostatic mechanism by which cells regulate levels of misfolded proteins in the endoplasmic reticulum (ER). Here, Hetz and Mollereau provide an overview of the most recent findings addressing the relevance of ER stress in the nervous system.
The unfolded protein response (UPR) is a homeostatic mechanism by which cells regulate levels of misfolded proteins in the endoplasmic reticulum (ER). Although it is well characterized in non-neuronal cells, a proliferation of papers over the past few years has revealed a key role for the UPR in normal neuronal function and as an important driver of neurodegenerative diseases. A complex scenario is emerging in which distinct UPR signalling modules have specific and even opposite effects on neurodegeneration depending on the disease context. Here, we provide an overview of the most recent findings addressing the biological relevance of ER stress in the nervous system.
Journal Article
شيرازيات : 75 قصيدة غزل مع 9 قصائد جديدة
كنت قد اخترت خمسة وسبعون قصيدة غزل من الشاعر والمتصوف الفارسي حافظ الشيرازي وعربتها مشيرا إلى أن عملي لم يكن ترجمة تتمتع بالأمانة الحرفية للنص الفارسي، لأن ذلك يقتل الشعر، بل منحتها روحي الشعرية وروح اللغة العربية معا، فظهرت أشبه ما تكون بنصوص على النصوص أو قصائد جديدة على قصائد قديمة، تنتمي إلي بمقدرا انتمائها لحافظ الشيرازي ومن يعرف اللغتين الفارسية والعربية يدرك مقاصد ما أقول.
Book
Impaired calcium signaling in astrocytes modulates autism spectrum disorder-like behaviors in mice
Autism spectrum disorder (ASD) is a common neurodevelopmental disorder. The mechanisms underlying ASD are unclear. Astrocyte alterations are noted in ASD patients and animal models. However, whether astrocyte dysfunction is causal or consequential to ASD-like phenotypes in mice is unresolved. Type 2 inositol 1,4,5-trisphosphate 6 receptors (IP3R2)-mediated Ca
2+
release from intracellular Ca
2+
stores results in the activation of astrocytes. Mutations of the IP3R2 gene are associated with ASD. Here, we show that both IP3R2-null mutant mice and astrocyte-specific IP3R2 conditional knockout mice display ASD-like behaviors, such as atypical social interaction and repetitive behavior. Furthermore, we show that astrocyte-derived ATP modulates ASD-like behavior through the P2X2 receptors in the prefrontal cortex and possibly through GABAergic synaptic transmission. These findings identify astrocyte-derived ATP as a potential molecular player in the pathophysiology of ASD.
Astrocytes contribute to autism spectrum disorder (ASD) pathophysiology. Here, the authors show that IP3R2 conditional KO mice show ASD-like behaviours and identify astrocyte-derived ATP as a modulator of these behaviours in mice.
Journal Article
كوميديا
يدور الحديث في هذا الكتاب ؛ حيث يجد القارئ أولا تصديرا عاما وموجزا يقف فيه فورا على العناصر الأساسية التي ينبغي معرفتها عن العمل وصاحبه ومكانته في الخلق الشعري وفيمن تكمن بعد ذلك سيقف القارئ على مدخل نقدي أو دراسي اعتمد فيه الباحث على عدد من القراءات الكبرى الموضوعة في دانتي و\"كوميدياه الإلهية\" (بورخيس وريسيه وجيرار وجاكوتيه والخ.) وتحمل هذه القراءات أكبر من التعمق والتفصيل.
Book
A mitotic chromatin phase transition prevents perforation by microtubules
Dividing eukaryotic cells package extremely long chromosomal DNA molecules into discrete bodies to enable microtubule-mediated transport of one genome copy to each of the newly forming daughter cells
1
–
3
. Assembly of mitotic chromosomes involves DNA looping by condensin
4
–
8
and chromatin compaction by global histone deacetylation
9
–
13
. Although condensin confers mechanical resistance to spindle pulling forces
14
–
16
, it is not known how histone deacetylation affects material properties and, as a consequence, segregation mechanics of mitotic chromosomes. Here we show how global histone deacetylation at the onset of mitosis induces a chromatin-intrinsic phase transition that endows chromosomes with the physical characteristics necessary for their precise movement during cell division. Deacetylation-mediated compaction of chromatin forms a structure dense in negative charge and allows mitotic chromosomes to resist perforation by microtubules as they are pushed to the metaphase plate. By contrast, hyperacetylated mitotic chromosomes lack a defined surface boundary, are frequently perforated by microtubules and are prone to missegregation. Our study highlights the different contributions of DNA loop formation and chromatin phase separation to genome segregation in dividing cells.
Histone deacetylation at the onset of mitosis induces a chromatin-intrinsic phase transition that endows chromosomes with the physical characteristics necessary for their precise movement during cell division.
Journal Article
الكوميديا الإلهية : المطهر
يتناول \"دانتي\" ما برح على عمله الشعري الأساسي في كتابه \"الكوميديا الإلهية\" يستنطق الحداثة الشعرية العالمية ويثير في مختلف اللغات الترجمة تلو الأخرى وقد كتب دانتي نفسه أن عمله قابل لقراءات متعددة، حرفية ورمزية، شعرية ولاهوتية وأمثولية (أليغورية). إلا أن القراءة الشعرية-الفلسفة هي السائدة اليوم. عن هذا العمل الإبداعي وعن صاحبه يدور الحديث في هذا الكتاب حيث يجد القارئ أولا تصديرا عاما وموجزا يقف فيه فورا على العناصر الأساسية التي ينبغي معرفتها عن العمل وصاحبه ومكانته في الخلق الشعري وفيمن تكمن. بعد ذلك سيقف القارئ على مدخل نقدي أو دراسي اعتمد فيه الباحث على عدد من القراءات الكبرى الموضوعة في دانتي و\"كوميدياه الإلهية\" (بورخيس، ريسيه، جيرار، جاكوتيه... إلخ) وتحمل هذه القراءات أكبر من التعمق والتفصيل وللقارئ أن يقرأ هذا المدخل قبل قراءة ترجمة الأجزاء الثلاثة بأنشوداتها المائة، أو أن يعود إلى قراءته بعد غوصه في العالم الشعري لدانتي.
Book
Immune evasion through mitochondrial transfer in the tumour microenvironment
Cancer cells in the tumour microenvironment use various mechanisms to evade the immune system, particularly T cell attack
1
. For example, metabolic reprogramming in the tumour microenvironment and mitochondrial dysfunction in tumour-infiltrating lymphocytes (TILs) impair antitumour immune responses
2
,
3
–
4
. However, detailed mechanisms of such processes remain unclear. Here we analyse clinical specimens and identify mitochondrial DNA (mtDNA) mutations in TILs that are shared with cancer cells. Moreover, mitochondria with mtDNA mutations from cancer cells are able to transfer to TILs. Typically, mitochondria in TILs readily undergo mitophagy through reactive oxygen species. However, mitochondria transferred from cancer cells do not undergo mitophagy, which we find is due to mitophagy-inhibitory molecules. These molecules attach to mitochondria and together are transferred to TILs, which results in homoplasmic replacement. T cells that acquire mtDNA mutations from cancer cells exhibit metabolic abnormalities and senescence, with defects in effector functions and memory formation. This in turn leads to impaired antitumour immunity both in vitro and in vivo. Accordingly, the presence of an mtDNA mutation in tumour tissue is a poor prognostic factor for immune checkpoint inhibitors in patients with melanoma or non-small-cell lung cancer. These findings reveal a previously unknown mechanism of cancer immune evasion through mitochondrial transfer and can contribute to the development of future cancer immunotherapies.
Mitochondria with mutations in their DNA from cancer cells can be transferred to T cells in the tumour microenvironment, which leads to T cell dysfunction and impaired antitumour immunity.
Journal Article