Combinatorial regulation of the balance between dynein microtubule end accumulation and initiation of directed motility
Cytoplasmic dynein is involved in a multitude of essential cellular functions. Dynein's activity is controlled by the combinatorial action of several regulatory proteins. The molecular mechanism of this regulation is still poorly understood. Using purified proteins, we reconstitute the regulation of the human dynein complex by three prominent regulators on dynamic microtubules in the presence of end binding proteins (EBs). We find that dynein can be in biochemically and functionally distinct pools: either tracking dynamic microtubule plus-ends in an EB-dependent manner or moving processively towards minus ends in an adaptor protein-dependent manner. Whereas both dynein pools share the dynactin complex, they have opposite preferences for binding other regulators, either the adaptor protein Bicaudal-D2 (BicD2) or the multifunctional regulator Lissencephaly-1 (Lis1). BicD2 and Lis1 together control the overall efficiency of motility initiation. Remarkably, dynactin can bias motility initiation locally from microtubule plus ends by autonomous plus-end recognition. This bias is further enhanced by EBs and Lis1. Our study provides insight into the mechanism of dynein regulation by dissecting the distinct functional contributions of the individual members of a dynein regulatory network.
Authors: Aseni P, Di Domenico SL, Barbosa F, Rampoldi A, Berry C Abstract Introduction: Hemoperitoneum can be a life-threating condition in cirrhotic patients who have a limited compensatory reserve during hemorrhagic shock. We aim to review the literature on the different etiologies associated with non-traumatic hemoperitoneum (NTH), summarizing the most relevant conditions associated with spontaneous and iatrogenic peritoneal and retroperitoneal bleeding that may occur in cirrhotic patients and to illustrate the most relevant diagnostic strategies and optimal management. Area covered: This review encompasses the ...
Conclusions: Between 2007 and 2010, endoscopic monitoring of patients within the first year after CD-related surgery was less than adequate based on current standards, but showed improvement. Medication changes were in general agreement with current guideline recommendations. This work was presented as a poster (number P686) by M. Barreiro-de Acosta et al. at ECCO (European Crohn's and Colitis Organisation) '18 in Vienna, Austria, 14-17 February 2018. PMID: 31203691 [PubMed - as supplied by publisher]
Authors: Haution D, Lala E, Le Lez ML, Laube N, Serrhini C, Jean-Lechner M, Dorvault M, Pisella PJ Abstract PURPOSE: To demonstrate a decrease in distance visual acuity (VA) following instillation of mydriatic eyedrops in eyes with exudative age-related macular degeneration (AMD). MATERIALS AND METHODS: A prospective assessment in clinical practice was conducted in our ophthalmology department at the University Hospital of Tours from 7/19/2018 to 8/29/2018. Distance (ETDRS) and near (Parinaud) VA were assessed before and after instilling one drop each of tropicamide 0.5% and phenylephrine 10% in the 40 included...
Authors: El Moize Z, Abdallah E, Benazzou S, Amazouzi A, Cherkaoui O PMID: 31204087 [PubMed - as supplied by publisher]
Authors: Albaroudi N, Tijani M, Boutimzine N, Cherkaoui O PMID: 31204086 [PubMed - as supplied by publisher]
DISCUSSION: Our data does not appear to suggest a significant protective effect of smoking on the occurrence of KC. It shows a lesser proportion of smokers in KC patients after A-CXL, but this difference did not exist at the time of KC diagnosis. PMID: 31204085 [PubMed - as supplied by publisher]
Conclusion: TIPS is an effective treatment for variceal bleeding and refractory ascites in most cases, but more than half of the patients experience either death, stent dysfunction, recurrence of symptoms, or overt HE within the first year after the procedure. PMID: 31203699 [PubMed - as supplied by publisher]
Conclusions: IBD causes a significant burden to the Finnish healthcare system. This study provides a detailed characterization of the cost landscape of IBD and contributes to optimizing treatment strategies and healthcare resource use in the biosimilar era. PMID: 31203693 [PubMed - as supplied by publisher]
Conclusion: Vascular abnormalities of the liver were commonly observed in thioguanine treated IBD patients, although these were not progressive and remained of limited clinical relevance over time. PMID: 31203688 [PubMed - as supplied by publisher]
In the past decade, there has been important movement in the recognition of adolescent health as a global concern, especially with the attention in the Sustainable Development Goals to adolescence as a period of both risk and opportunity [1,2]. Increasingly, international frameworks, commitments, research, and advocacy are acknowledging the complex and distinct health burden that girls and boys face during adolescence [3 –6]. The Lancet Commission on Adolescent Health and Wellbeing consolidated important patterns and insights not only regarding the nature of this burden but also on the range of interventions and poli...
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