ResearchPad - 27 https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Renaissance of Radiotherapy in Intestinal Lymphoma? 10‐Year Efficacy and Tolerance in Multimodal Treatment of 134 Patients: Follow‐up of Two German Multicenter Consecutive Prospective Phase II Trials]]> https://www.researchpad.co/article/elastic_article_6608 This article reports the details of radiation therapy in the therapeutic multimodality approach for treatment of patients with intestinal lymphoma.

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<![CDATA[Wednesday posters]]> https://www.researchpad.co/article/N19c7ed87-c80c-46f1-bedc-4ddeabe0c3eb ]]> <![CDATA[Thursday posters]]> https://www.researchpad.co/article/N50c37668-91e9-43b8-aadf-3c08854ae4fc ]]> <![CDATA[Follicular Lymphoma: Recent and Emerging Therapies, Treatment Strategies, and Remaining Unmet Needs]]> https://www.researchpad.co/article/N7a398851-26bc-430e-8974-6404fe55ba85

Therapeutic advances have improved prognosis for follicular lymphoma, although the disease is still incurable. This comprehensive clinical review considers prognostic approaches and the treatment landscape for follicular lymphoma, including emerging therapies and unmet needs.

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<![CDATA[Measuring mRNA translation in neuronal processes and somata by tRNA-FRET]]> https://www.researchpad.co/article/N26eefdd3-9a89-43fc-a876-adf8b7011d56

Abstract

In neurons, the specific spatial and temporal localization of protein synthesis is of great importance for function and survival. Here, we visualized tRNA and protein synthesis events in fixed and live mouse primary cortical culture using fluorescently-labeled tRNAs. We were able to characterize the distribution and transport of tRNAs in different neuronal sub-compartments and to study their association with the ribosome. We found that tRNA mobility in neural processes is lower than in somata and corresponds to patterns of slow transport mechanisms, and that larger tRNA puncta co-localize with translational machinery components and are likely the functional fraction. Furthermore, chemical induction of long-term potentiation (LTP) in culture revealed up-regulation of mRNA translation with a similar effect in dendrites and somata, which appeared to be GluR-dependent 6 h post-activation. Importantly, measurement of protein synthesis in neurons with high resolutions offers new insights into neuronal function in health and disease states.

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<![CDATA[Assembling nuclear domains: Lessons from DNA repair]]> https://www.researchpad.co/article/Nd5296de9-d84a-44e2-a392-db9b4e326f26

Schrank and Gautier discuss the generation and function of nuclear domains during DNA repair with a special focus on nuclear actin polymerization.

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<![CDATA[Patient‐Reported Factors in Treatment Satisfaction in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)]]> https://www.researchpad.co/article/Nfdd5adc1-7a36-4abe-aa96-680ed7098c6d

This article identifies factors associated with patient‐reported satisfaction with multiple myeloma therapy and the treatment‐related time burden and indirect costs among patients with relapsed or refractory multiple myeloma and their caregivers. Improved understanding of these variables will inform treatment decisions across this complex treatment landscape.

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<![CDATA[1q21 Gain Combined with High‐Risk Factors Is a Heterogeneous Prognostic Factor in Newly Diagnosed Multiple Myeloma: A Multicenter Study in China]]> https://www.researchpad.co/article/N683fc359-39b8-45eb-b872-ae285a98de50

The identification of prognostic factors for multiple myeloma is important. This article focuses on the prognostic value of 1q21 gain in a Chinese population according to different treatment regimens and accompanying high‐risk factors.

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<![CDATA[Tumor Lysis Syndrome in Chronic Lymphocytic Leukemia with Novel Targeted Agents]]> https://www.researchpad.co/article/5c11c06ad5eed0c484783f66

Tumor lysis syndrome is an uncommon but potentially life‐threatening complication associated with the treatment of some cancers. In this review, prevention strategies and management of patients with chronic lymphocytic leukemia who develop tumor lysis syndrome are described.

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<![CDATA[Dissecting the role of His domain protein tyrosine phosphatase/PTPN23 and ESCRTs in sorting activated epidermal growth factor receptor to the multivesicular body]]> https://www.researchpad.co/article/5c114480d5eed0c4845d3d2f

Sorting of activated epidermal growth factor receptor (EGFR) into intraluminal vesicles (ILVs) within the multivesicular body (MVB) is an essential step during the down-regulation of the receptor. The machinery that drives EGFR sorting attaches to the cytoplasmic face of the endosome and generates vesicles that bud into the endosome lumen, but somehow escapes encapsulation itself. This machinery is termed the ESCRT (endosomal sorting complexes required for transport) pathway, a series of multi-protein complexes and accessory factors first identified in yeast. Here, we review the yeast ESCRT pathway and describe the corresponding components in mammalian cells that sort EGFR. One of these is His domain protein tyrosine phosphatase (HD-PTP/PTPN23), and we review the interactions involving HD-PTP and ESCRTs. Finally, we describe a working model for how this ESCRT pathway might overcome the intrinsic topographical problem of EGFR sorting to the MVB lumen.

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<![CDATA[Towards a therapy for mitochondrial disease: an update]]> https://www.researchpad.co/article/5c11447cd5eed0c4845d3c78

Preclinical work aimed at developing new therapies for mitochondrial diseases has recently given new hopes and opened unexpected perspectives for the patients affected by these pathologies. In contrast, only minor progresses have been achieved so far in the translation into the clinics. Many challenges are still ahead, including the need for a better characterization of the pharmacological effects of the different approaches and the design of appropriate clinical trials with robust outcome measures for this extremely heterogeneous, rare, and complex group of disorders. In this review, we will discuss the most important achievements and the major challenges in this very dynamic research field.

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<![CDATA[Roles for ER:endosome membrane contact sites in ligand-stimulated intraluminal vesicle formation]]> https://www.researchpad.co/article/5c11447ed5eed0c4845d3cb4

Multivesicular endosomes/bodies (MVBs) sort membrane proteins between recycling and degradative pathways. Segregation of membrane proteins onto intraluminal vesicles (ILVs) of MVBs removes them from the recycling pathway and facilitates their degradation following fusion of MVBs with lysosomes. Sorting of many cargos onto ILVs depends on the ESCRT (Endosomal Sorting Complex Required for Transport) machinery, although ESCRT-independent mechanisms also exist. In mammalian cells, efficient sorting of ligand-stimulated epidermal growth factor receptors onto ILVs also depends on the tyrosine phosphatase, PTP1B, an ER-localised enzyme that interacts with endosomal targets at membrane contacts between MVBs and the ER. This review focuses on the potential roles played by ER:MVB membrane contact sites in regulating ESCRT-dependent ILV formation.

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<![CDATA[Fanconi anemia FANCD2 and FANCI proteins regulate the nuclear dynamics of splicing factors]]> https://www.researchpad.co/article/5c01f900d5eed0c4842bf801

Moriel-Carretero et al. show that the Fanconi anemia proteins FANCI and FANCD2 associate with the splicing factor SF3B1 and that DNA replication stress induces the FANCI-dependent release of SF3B1 from nuclear speckles. FANCI and FANCD2 prevent accumulation of postcatalytic intron lariats, suggesting that they help coordinate DNA replication and transcription.

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<![CDATA[RECQ-like helicases Sgs1 and BLM regulate R-loop–associated genome instability]]> https://www.researchpad.co/article/5c01f90fd5eed0c4842bfc72

Chang et al. link the RECQ-like helicase BLM and its yeast orthologue Sgs1 to preventing DNA damage caused by the accumulation of DNA:RNA hybrid structures called R-loops. This adds to a growing family of helicases implicated in R-loop resolution.

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<![CDATA[Chromosome biorientation and APC activity remain uncoupled in oocytes with reduced volume]]> https://www.researchpad.co/article/5c01f8ecd5eed0c4842bf32d

Lane and Jones use serial bisection of mouse oocytes to analyze the influence of cytoplasmic volume on spindle assembly checkpoint function. Volume reduction promotes inhibition of APC but cannot prevent chromosome segregation errors at anaphase.

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<![CDATA[Autophagy balances mtDNA synthesis and degradation by DNA polymerase POLG during starvation]]> https://www.researchpad.co/article/5c129a86d5eed0c4848c8427

Medeiros et al. show that mtDNA polymerase POLG controls mtDNA copy number in the context of autophagy-mediated metabolic homeostasis. After prolonged starvation, the mtDNA degradative activity of POLG is activated to adjust the increasing mtDNA copy number in WT cells, whereas in autophagy-deficient cells, POLG’s continued degradative activity causes mtDNA instability and respiratory dysfunction as a result of nucleotide insufficiency.

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<![CDATA[DNA replication licensing in stem cells: Gatekeeping the commitment to proliferation]]> https://www.researchpad.co/article/5c129a88d5eed0c4848c8447

Coller previews work from the Carroll et al. identifying proliferative intestinal stem cells in an unlicensed state, providing insight into what controls the transition between quiescence and proliferation.

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<![CDATA[Long-term correlation of the electrocorticogram as a bioindicator of brain exposure to ionizing radiation]]> https://www.researchpad.co/article/5af45b88463d7e03109a6221

Understanding the effects of radiation and its possible influence on the nervous system are of great clinical interest. However, there have been few electrophysiological studies on brain activity after exposure to ionizing radiation (IR). A new methodological approach regarding the assessment of the possible effects of IR on brain activity is the use of linear and nonlinear mathematical methods in the analysis of complex time series, such as brain oscillations measured using the electrocorticogram (ECoG). The objective of this study was to use linear and nonlinear mathematical methods as biomarkers of gamma radiation regarding cortical electrical activity. Adult Wistar rats were divided into 3 groups: 1 control and 2 irradiated groups, evaluated at 24 h (IR24) and 90 days (IR90) after exposure to 18 Gy of gamma radiation from a cobalt-60 radiotherapy source. The ECoG was analyzed using power spectrum methods for the calculation of the power of delta, theta, alpha and beta rhythms and by means of the α-exponent of the detrended fluctuation analysis (DFA). Using both mathematical methods it was possible to identify changes in the ECoG, and to identify significant changes in the pattern of the recording at 24 h after irradiation. Some of these changes were persistent at 90 days after exposure to IR. In particular, the theta wave using the two methods showed higher sensitivity than other waves, suggesting that it is a possible biomarker of exposure to IR.

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<![CDATA[GPI-anchored proteins are confined in subdiffraction clusters at the apical surface of polarized epithelial cells]]> https://www.researchpad.co/article/5b467a0a463d7e5f40bc6dde

Spatio-temporal compartmentalization of membrane proteins is critical for the regulation of diverse vital functions in eukaryotic cells. It was previously shown that, at the apical surface of polarized MDCK cells, glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are organized in small cholesterol-independent clusters of single GPI-AP species (homoclusters), which are required for the formation of larger cholesterol-dependent clusters formed by multiple GPI-AP species (heteroclusters). This clustered organization is crucial for the biological activities of GPI-APs; hence, understanding the spatio-temporal properties of their membrane organization is of fundamental importance. Here, by using direct stochastic optical reconstruction microscopy coupled to pair correlation analysis (pc-STORM), we were able to visualize and measure the size of these clusters. Specifically, we show that they are non-randomly distributed and have an average size of 67 nm. We also demonstrated that polarized MDCK and non-polarized CHO cells have similar cluster distribution and size, but different sensitivity to cholesterol depletion. Finally, we derived a model that allowed a quantitative characterization of the cluster organization of GPI-APs at the apical surface of polarized MDCK cells for the first time. Experimental FRET (fluorescence resonance energy transfer)/FLIM (fluorescence-lifetime imaging microscopy) data were correlated to the theoretical predictions of the model.

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