tbuckley/cabot-search huggingface dataset:
Abstract 12231: PECAM1 is Essential for Flow-mediated Gab1 Tyrosine Phosphorylation and Signaling <i>in vitro</i> and <i>in vivo</i>
Authors: Suowen Xu, Marina Koroleva, Keigi Fujiwara, Zheng Gen Jin
Journal: Circulation (2015)

Introduction: Impaired activation of endothelial nitric oxide (NO) synthase (eNOS) and ensued NO production is a common mechanism of various cardiovascular pathologies, including hypertension and atherosclerosis. Specific signaling cascades, generated by vascular endothelial cells (ECs) in response to laminar flow, modulate EC structure and functions, NO production in particular. We have previously shown that flow-stimulated Gab1 (Grb2-associated binder-1) tyrosine phosphorylation mediates eNOS activation. However, the upstream mechanism that regulates Gab1 tyrosine phosphorylation remains unclear. Hypothesis: We hypothesized that platelet endothelial cell adhesion molecule-1 (PECAM1), a key molecule in an endothelial mechanosensing complex, specifically mediates Gab1 tyrosine phosphorylation and its downstream Akt and eNOS activation in ECs upon flow rather than hepatocyte growth factor (HGF) stimulation. Methods: Western blot, en face staining and voluntary wheel running. Results: Small interfering RNA (siRNA) targeting PECAM1 abolished flow- but not HGF-induced Gab1 tyrosine phosphorylation and Akt, eNOS activation as well as Gab1 membrane translocation. Protein-tyrosine phosphatase SHP2, which has been shown to interact with Gab1, was involved in a flow signaling pathway as well as HGF-induced signaling, as SHP2 siRNA diminished the flow- and HGF-induced Gab1 tyrosine phosphorylation, membrane localization and downstream signaling. Pharmacological inhibition of PI3K by LY294002 decreased flow, but not HGF-mediated Gab1 phosphorylation and membrane localization as well as eNOS activation. Finally, we observed that flow-mediated Gab1 and eNOS phosphorylation in vivo induced by voluntary wheel running was reduced in PECAM1 knockout mice. Conclusions: These results demonstrate a specific role of PECAM1 in flow-mediated Gab1 tyrosine phosphorylation and eNOS signaling in ECs
Regulation of cell-type-specific transcriptomes by microRNA networks during human brain development
Authors: Tomasz J. Nowakowski, Neha Rani, Mahdi Golkaram, Hongjun R. Zhou, Beatriz Alvarado, Kylie Huch, Jay A. West, Anne Leyrat, Alex A. Pollen, Arnold R. Kriegstein, Linda R. Petzold, Kenneth S. Kosik
Journal: Nature Neuroscience (2018)
Состояние эндогенной интоксикации и иммуновоспалительной реакции у больных с алкогольным циррозом печени в сочетании с неалкогольной жировой болезнью печени
Authors: N.R. Matkovska, N.H. Virstiuk, U.V. Balan
Journal: GASTROENTEROLOGY (2019)

Цель: оценить состояние эндогенной интоксикации у пациентов с алкогольным циррозом печени (АЦП) при сочетании с неалкогольной жировой болезнью печени (НАЖБП) в зависимости от стадии декомпенсации. Материалы и методы. Обследовано 204 пациента. Среди них у 78 человек (I группа) диагностирован АЦП и у 126 лиц (II группа) было сочетание АЦП с НАЖБП. Пациентов разделили на подгруппы в зависимости от классов компенсации по критериям Чайлда — Пью (А, В, С). Проведены общеклинические и инструментальные обследования. Определяли лейкоцитарный индекс интоксикации (ЛИИ), сорбционную способность эритроцитов (ССЭ), уровень резистина, высокочувствительного С-реактивного белка (вч-СРБ) и фактора некроза опухоли α (ФНО-α) в крови. Результаты. У пациентов с сочетанием АЦП и НАЖБП наблюдалась более тяжелая клиническая картина с развитием астеновегетативного, болевого, диспептического, гепаторенального, гепатопульмонального синдромов, желтухи, портальной гипертензии, печеночной энцефалопатии. Отмечались такие тяжелые инфекционные осложнения, как пневмония и спонтанный бактериальный перитонит, чаще у пациентов с субкомпенсацией и декомпенсацией. У всех больных ССЭ, ЛИИ и показатели ФНО-α, вч-СРБ, резистина увеличивались с нарастанием декомпенсации заболевания. Повышенные ССЭ, ЛИИ и более высокие уровни ФНО-α, вч-СРБ и резистина в сыворотке крови наблюдались при сочетании АЦП и НАЖБП, что связано с более тяжелым течением патологического состояния у таких больных. Мы обнаружили положительные связи между уровнем резистина и ФНО-α, вч-СРБ, ССЭ, ЛИИ. Такие результаты свидетельствуют об участии резистина в иммуновоспалительных процессах и развитии эндогенной интоксикации при АЦП. Выводы. С нарастанием декомпенсации АЦП при сочетании с НАЖБП увеличивается степень эндогенной интоксикации, которая сопровождается развитием иммуновоспалительной реакции, о чем свидетельствуют повышенные ССЭ, ЛИИ, а также более высокие уровни ФНО-α, вч-СРБ и резистина. Достоверно более высокие ССЭ, ЛИИ и уровни ФНО-α, вч-СРБ и резистина выявлены у больных при сочетании АЦП с НАЖБП, что сопровождается более тяжелым течением заболевания. У пациентов с АЦП и НАЖХП обнаружены корреляции между уровнем резистина и ФНО-α, вч-СРБ, ССЭ, ЛИИ.
Identifying Clusters of High Confidence Homologies in Multiple Sequence Alignments
Authors: Raja Hashim Ali, Marcin Bogusz, Simon Whelan
Journal: Molecular Biology and Evolution (2019)

Multiple sequence alignment (MSA) is ubiquitous in evolution and bioinformatics. MSAs are usually taken to be a known and fixed quantity on which to perform downstream analysis despite extensive evidence that MSA accuracy and uncertainty affect results. These errors are known to cause a wide range of problems for downstream evolutionary inference, ranging from false inference of positive selection to long branch attraction artifacts. The most popular approach to dealing with this problem is to remove (filter) specific columns in the MSA that are thought to be prone to error. Although popular, this approach has had mixed success and several studies have even suggested that filtering might be detrimental to phylogenetic studies. We present a graph-based clustering method to address MSA uncertainty and error in the software Divvier (available at https://github.com/simonwhelan/Divvier), which uses a probabilistic model to identify clusters of characters that have strong statistical evidence of shared homology. These clusters can then be used to either filter characters from the MSA (partial filtering) or represent each of the clusters in a new column (divvying). We validate Divvier through its performance on real and simulated benchmarks, finding Divvier substantially outperforms existing filtering software by retaining more true pairwise homologies calls and removing more false positive pairwise homologies. We also find that Divvier, in contrast to other filtering tools, can alleviate long branch attraction artifacts induced by MSA and reduces the variation in tree estimates caused by MSA uncertainty.
AB1362-HPR THE EFFECTS OF 4 – WEEK REHABILITATION PROGRAM ON PATIENT OUTCOMES IN PATIENTS WITH KNEE OSTEOARTHRITIS
Authors: Onur Aydogdu, Sefer Kılıçkap, Beyzanur Daşkın, Zübeyir Sarı
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Osteoarthritis (OA) is the most common form of arthritis and a major cause of pain and disability in older adults (1). Older adults with knee OA report lower physical functioning and increased difficulty in performing activities of daily living compared with older adults without knee OA (2). Knee OA treatment aims to improve physical functions, quality of life, prevent disability, and decrease pain. Therapeutic exercises and physiotherapy treatment applications are recommended for the patients with knee OA (3). <h3>Objectives</h3> The purpose of this study was to examine the effects of 4 week physiotherapy and rehabilitation program on range of motion, balance, knee swelling, and activities of daily life, quality of life, and functional status in patients with knee osteoarthritis. It was hypothesized that 4 week rehabilitation program might provide improvements in measurements of the patient outcomes in patients with knee osteoarthritis. <h3>Methods</h3> Twenty-seven healthy subjects were participated in the study. Subjects had no surgery history of lower extremity. Range of motion, balance, knee swelling, activities of daily life, quality of life, and functional status were assessed by Goniometer, Berg Balance Test, Tape measure, Barthel Index, WHOQL Scale, WOMAC Scale, respectively. The physiotherapy and rehabilitation program started after the first assessment and was applied as 20 sessions for a total of four weeks, five sessions per week. All of the assessments procedures were performed again after the treatment. <h3>Results</h3> There were statistically significant improvements in measures of range of motion, balance, knee swelling, and functional status between pre- and post treatment (p&lt;0.05). However, no significant difference was found in activities of daily life and quality of life after the 4-week rehabilitation program (p&gt;0.05). <h3>Conclusion</h3> Based on our findings, short-term effects of physiotherapy and rehabilitation program may be beneficial on range of motion, balance, knee swelling, and functional status in patients with knee osteoarthritis. However, 4-week rehabilitation program has no effect on activities of daily life and quality of life in patients with knee osteoarthritis. <h3>References</h3> [1] Huang L, Guo B, Xu F, Zhao J. Effects of quadriceps functional exercise with isometric contraction in the treatment of knee osteoarthritis. Int J Rheum Dis. 2018 May;21(5):952-959. [2] Mihalko SL, Cox P, Beavers DP, et al. Effect of intensive diet and exercise on self-efficacy in overweight and obese adults with knee osteoarthritis: The IDEA randomized clinical trial. Transl Behav Med. 2018 Apr 4. [3] 3Aydoğdu O, Sari Z, Yurdalan SU, Polat MG. Clinical outcomes of kinesio taping applied in patients with knee osteoarthritis: A randomized controlled trial. J Back Musculoskelet Rehabil. 2017 Sep 22;30(5):1045-1051. <h3>Disclosure of Interests</h3> None declared
AB0223 ASSESSMENT OF DISEASE ACTIVITY IN SYSTEMIC SCLEROSIS: THE COMPARISON BETWEEN REVISED EUSTAR AND ESCSG ACTIVITY INDEXES
Authors: Yasemin Yalçınkaya, ümmügülsüm Gazel, Sema Kaymaz Tahra, Aysun Aksoy, Murat Karabacak, Seda Kutluğ, Ozlem Pehlivan, Fatma Alibaz-Oner, Pamir Atagündüz, Nevsun Inanc, Haner Direskeneli
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Assessment of disease activity in systemic sclerosis (SSc) is challenging and usually hard to distinguish from damage or chronicity. <h3>Objectives</h3> We aimed to evaluate disease activity by different indexes and compare them in a SSc cohort. <h3>Methods</h3> Disease activity was evaluated by revised EUSTAR (European Scleroderma Trials and Research group) and EScSG (European Scleroderma Study Group) activity indexes in 131 SSc patients fullfiling ACR/EULAR classification criteria (2013). The patients with the scores of EUSTAR activity index ≥2.5 or EScSG activity index ≥3 were accepted as having active disease. <h3>Results</h3> Demographics, disease characteristics and nailfold video-capillaroscopic (NVC) pattern details were summarised in table-1. The scores of EUSTAR and EScSG activity indexes were correlated well (r=0.576, p=0.000) and the agreement between two scores for activity was moderate (cohen kappa:0.407). The percentages of SSc patients described as having active disease or not according to two activity indexes were summarised in table-2. Of the patients, 9.9% had active and 70.9% had inactive disease according to both indexes in this SSc cohort. Twenty -one (for EUSTAR) and 4 patients (for EScSG) were described as active according to one index and not to the other. Revised EUSTAR activity index was found to have 76.5% sensitivity and 81.6% specificity when the activity was defined by EScSG activity index. <h3>Conclusion</h3> This SSc cohort predominantly had limited cutanous disease, digital vasculopathy and late scleroderma pattern. Defining active disease was differed in 19% of the patients according to EUSTAR and EScSG activity indexes, former described higher frequency for activity. This difference might be related to validation procedures of these indexes in patients with different predominant stages of SSc disease, content of the index and the features of the cohort. <h3>Disclosure of Interests</h3> None declared
Abstract 16421: Inhibition of Bone Morphogenetic Protein (BMP) Signaling Mitigates Nonalcoholic Fatty Liver Disease (NAFLD) and Identification of an Activating BMP Receptor Polymorphism Associated With NAFLD
Authors: Timothy E Thayer, Trejeeve Martin, Hannah Shakartzi, Florian Wunderer, Daniel Perrien, Eric Farber-Eger, Megan Burke, Emmanuel Buys, Caitlin O'Rouke, Georgia Shelton, Jason Li, Donald Bloch, Quinn Wells, Charles Hong, Rajeev Malhotra
Journal: Circulation (2017)

Introduction: One third of adults in the US have NAFLD, a disease characterized by accumulation of triglycerides (TG) in the liver. NAFLD is an independent risk factor for coronary artery disease. ...
AB1184 BONE MINERAL DENSITY, TRABECULAR BONE SCORE AND 3D-DXA ASSESSMENT IN ADULT PATIENTSWITH A POSITIVE AND NEGATIVE GENETICAL TESTING FOR HYPOPHOSPHATASIA
Authors: Carolina Tornero, Monica Coronado, Ludovic Humbert, Sara García-Carazo, Carmen Lancha, Domenico Monachello, Luis Dominguez-Gadea, Alejandro Balsa, Pilar Aguado
Journal: Annals of the Rheumatic Diseases (2019)

correlation with DAS28.In contrast, GS joint inflammation is associated with structural joint damage and has strong correlation with US-detected erosion.
Fluidised bed granulation of two APIs: QbD approach and development of a NIR in-line monitoring method
Authors: Alexandru Gavan, Sonia Iurian, Tibor Casian, Alina Porfire, Sebastian Porav, Ioana Voina, Alexandru Oprea, Ioan Tomuta
Journal: Asian Journal of Pharmaceutical Sciences (2019)

The study focused on the fluid-bed granulation process of a product with two active pharmaceutical ingredients, intended for coated tablets preparation and further transfer to industrial scale. The work aimed to prove that an accurate control of the critical granulation parameters can level the input material variability and offer a user-friendly process control strategy. Moreover, an in-line Near-Infrared monitoring method was developed, which offered a real time overview of the moisture level along the granulation process, thus a reliable supervision and control process analytical technology (PAT) tool. The experimental design's results showed that the use of apparently interchangeable active pharmaceutical ingredients (APIs) and filler sorts that comply with pharmacopoeial specifications, lead to different end-product critical attributes. By adapting critical granulation parameters (i.e. binder spray rate and atomising pressure) as a function of material characteristics, led to granules with average sizes comprised in a narrow range of 280–320 µm and low non-granulated fraction of under 5%. Therefore, the accurate control of process parameters according to the formulation particularities achieved the maintenance of product within the design space and removed material related variability. To complete the Quality by design (QbD) strategy, despite its limited spectral domain, the microNIR spectrometer was successfully used as a robust PAT monitoring tool that offered a real time overview of the moisture level and allowed the supervision and control of the granulation process.
Multifunctional low-temperature photothermal nanodrug with in vivo clearance, ROS-Scavenging and anti-inflammatory abilities
Authors: Gang-Gang Yang, Dan-Jie Zhou, Zheng-Yin Pan, Jing Yang, Dong-Yang Zhang, Qian Cao, Liang-Nian Ji, Zong-Wan Mao
Journal: Biomaterials (2019)
Links between environment, diet, and the hunter-gatherer microbiome
Authors: Gabriela K. Fragiadakis, Samuel A. Smits, Erica D. Sonnenburg, William Van Treuren, Gregor Reid, Rob Knight, Alphaxard Manjurano, John Changalucha, Maria Gloria Dominguez-Bello, Jeff Leach, Justin L. Sonnenburg
Journal: Gut Microbes (2018)

The study of traditional populations provides a view of human-associated microbes unperturbed by industrialization, as well as a window into the microbiota that co-evolved with humans. Here we discuss our recent work characterizing the microbiota from the Hadza hunter-gatherers of Tanzania. We found seasonal shifts in bacterial taxa, diversity, and carbohydrate utilization by the microbiota. When compared to the microbiota composition from other populations around the world, the Hadza microbiota shares bacterial families with other traditional societies that are rare or absent from microbiotas of industrialized nations. We present additional observations from the Hadza microbiota and their lifestyle and environment, including microbes detected on hands, water, and animal sources, how the microbiota varies with sex and age, and the short-term effects of introducing agricultural products into the diet. In the context of our previously published findings and of these additional observations, we discuss a path forward for future work.
SP0022 PROJECT ABSTRACT 2: EMERGE – HELPING DELIVER OUR WORLDWIDE GOALS
Authors: Lovro Lamot
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> EMERGE (EMErging Rheumatologist and rEsearchers) is a new group of young physicians and scientists from across the globe with a shared interest and passion for pediatric rheumatology. Amid numerous differences in education, research opportunities and healthcare systems across countries, the overarching aim of the group is to work closely together towards the same goal of providing a best possible care for children with rheumatic diseases. With the support of the Pediatric Rheumatology European Society (PReS), the group has created several compelling initiatives which could help the creation of a new generation of professionals who can deliver this goal. Therefore, one the paramount initiative of the group is the PReS EMERGE fellowship. This unique program enables clinicians and scientist from all over the world to come to the established pediatric rheumatology centers in Europe, receive clinical or translational research training, perform a short study and build a support network readily available after returning to their surroundings. Next, the Peer Review Mentoring Program has been recently started in order to provide a first structured peer review training in the field of pediatric rheumatology. The prevailing intention of this initiative is to improve the quality of published researches by education of the future peer reviewers. The important initiative of the group is also the organization of the Young Investigators Meeting (YIM), that takes place every year before the PReS congress. This meeting gathers many clinicians and scientist from all continents and provides them with an excellent opportunity of presenting their basic and clinical discoveries and compelling cases to their peers and "not so senior" faculty. Besides, the group is involved in the organization of many educational courses where world-leading experts are conveying their experience and knowledge of a particular topic. To succeed in these initiatives, the EMERGE group is working closely with other similar groups, such as CARRA young investigators from North America and EMEUNET group of young adult rheumatologist from Europe. Moreover, the group has a firm collaboration with Pediatric Task Force Global Musculoskeletal Health, a group dedicated to raising the awareness and improving access to right care for children with musculoskeletal diseases, and ENCA, a network of national associations working with children and young people with pediatric rheumatic diseases. Finally, in order to spread information about these initiatives and to attract new members, the group is actively using social media platforms, such as Facebook (https://www.facebook.com/PReSEMERGE/), Twitter (@PReSEMERGE), and bi-monthly newsletters (emerge.pres@gmail.com). <h3>Disclosure of Interests:</h3> None declared
Loss of Protein Phosphatase 1 Regulatory Subunit PPP1R3A Promotes Atrial Fibrillation
Authors: Katherina M. Alsina, Mohit Hulsurkar, Sören Brandenburg, Daniel Kownatzki-Danger, Christof Lenz, Henning Urlaub, Issam Abu-Taha, Markus Kamler, David Y. Chiang, Satadru K. Lahiri, Julia O. Reynolds, Ann P. Quick, Larry Scott, Tarah A. Word, Maria D. Gelves, Albert J.R. Heck, Na Li, Dobromir Dobrev, Stephan E. Lehnart, Xander H.T. Wehrens
Journal: Circulation (2019)

Abnormal calcium (Ca2+) release from the sarcoplasmic reticulum (SR) contributes to the pathogenesis of atrial fibrillation (AF). Increased phosphorylation of 2 proteins essential for normal SR-Ca2+ cycling, the type-2 ryanodine receptor (RyR2) and phospholamban (PLN), enhances the susceptibility to AF, but the underlying mechanisms remain unclear. Protein phosphatase 1 (PP1) limits steady-state phosphorylation of both RyR2 and PLN. Proteomic analysis uncovered a novel PP1-regulatory subunit (PPP1R3A [PP1 regulatory subunit type 3A]) in the RyR2 macromolecular channel complex that has been previously shown to mediate PP1 targeting to PLN. We tested the hypothesis that reduced PPP1R3A levels contribute to AF pathogenesis by reducing PP1 binding to both RyR2 and PLN.Immunoprecipitation, mass spectrometry, and complexome profiling were performed from the atrial tissue of patients with AF and from cardiac lysates of wild-type and Pln-knockout mice. Ppp1r3a-knockout mice were generated by CRISPR-mediated deletion of exons 2 to 3. Ppp1r3a-knockout mice and wild-type littermates were subjected to in vivo programmed electrical stimulation to determine AF susceptibility. Isolated atrial cardiomyocytes were used for Stimulated Emission Depletion superresolution microscopy and confocal Ca2+ imaging.Proteomics identified the PP1-regulatory subunit PPP1R3A as a novel RyR2-binding partner, and coimmunoprecipitation confirmed PPP1R3A binding to RyR2 and PLN. Complexome profiling and Stimulated Emission Depletion imaging revealed that PLN is present in the PPP1R3A-RyR2 interaction, suggesting the existence of a previously unknown SR nanodomain composed of both RyR2 and PLN/sarco/endoplasmic reticulum calcium ATPase-2a macromolecular complexes. This novel RyR2/PLN/sarco/endoplasmic reticulum calcium ATPase-2a complex was also identified in human atria. Genetic ablation of Ppp1r3a in mice impaired binding of PP1 to both RyR2 and PLN. Reduced PP1 targeting was associated with increased phosphorylation of RyR2 and PLN, aberrant SR-Ca2+ release in atrial cardiomyocytes, and enhanced susceptibility to pacing-induced AF. Finally, PPP1R3A was progressively downregulated in the atria of patients with paroxysmal and persistent (chronic) AF.PPP1R3A is a novel PP1-regulatory subunit within the RyR2 channel complex. Reduced PPP1R3A levels impair PP1 targeting and increase phosphorylation of both RyR2 and PLN. PPP1R3A deficiency promotes abnormal SR-Ca2+ release and increases AF susceptibility in mice. Given that PPP1R3A is downregulated in patients with AF, this regulatory subunit may represent a new target for AF therapeutic strategies.
Abstract 18301: The Longitudinal Decline in Ankle-Brachial Index is Paralleled With Reduction in Peripheral-to-Central Arterial Stiffness With Aging: The Baltimore Longitudinal Stud of Aging
Authors: Majd AlGhatrif, Matt Oberdier, Chris Morrell, Stephanie Studenski, Edward G Lakatta
Journal: Circulation (2016)

Introduction: The physiologically greater ankle than arm pressure, represented by ABI >1, is attributed to the physiologically stiffer leg than central arteries. This relationship, however, changes...