Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of cell adhesion: a collaborative effort of integrins, their ligands, cytoplasmic actors, and phosphorylation

Abstract Integrins are large heterodimeric type 1 membrane proteins expressed in all nucleated mammalian cells. Eighteen α-chains and eight β-chains can combine to form 24 different integrins. They are cell adhesion proteins, which bind to a large variety of cellular and extracellular ligands. Integrins are required for cell migration, hemostasis, translocation of cells out from the blood stream and further movement into tissues, but also for the immune response and tissue morphogenesis. Importantly, integrins are not usually active as such, but need activation to become adhesive. Integrins are activated by outside-in activation through integrin ligand binding, or by inside-out activation through intracellular signaling. An important question is how integrin activity is regulated, and this topic has recently drawn much attention. Changes in integrin affinity for ligand binding are due to allosteric structural alterations, but equally important are avidity changes due to integrin clustering in the plane of the plasma membrane. Recent studies have partially solved how integrin cell surface structures change during activation. The integrin cytoplasmic domains are relatively short, but by interacting with a variety of cytoplasmic proteins in a regulated manner, the integrins acquire a number of properties important not only for cell adhesion and movement, but also for cellular signaling. Recent work has shown that specific integrin phosphorylations play pivotal roles in the regulation of integrin activity. Our purpose in this review is to integrate the present knowledge to enable an understanding of how cell adhesion is dynamically regulated.
STRATEGIES FOR THE MANAGEMENT OF OPIOID-INDUCED ADVERSE EFFECTS

Opioids have the potential to produce a broad range of adverse events, including sedation, respiratory depression, nausea, vomiting, and constipation. Many of these adverse effects diminish over time as tolerance develops, although tolerance to some effects develops very slowly or not at all. The adverse event profiles of the various opioids are generally similar when administered at equianalgesic doses, although individual patients may respond differently to the various agents. In addition, some opioids (eg, meperidine and propoxyphene) are associated with relatively high rates of adverse events, and are not recommended as first-line analgesics. Sedation and nausea are common with opioid initiation or dose escalation, and may be exacerbated by a number of other medications or comorbid conditions. Opioids produce a number of central and peripheral effects that contribute to nausea and vomiting. Constipation is very common with opioid therapy, and is generally not significantly relieved by the development of tolerance. A bowel regimen that includes a stool softener and a stimulant laxative is essential for every patient who is using an opioid analgesic. Bulkforming laxatives are not recommended for patients taking opioids. Strategies to reduce opioid-induced adverse events include cautious dosage titration, dose reduction, management of specific symptoms, opioid rotation, or using a different route of administration. Opioid conversion may be calculated using published conversion charts, but must be individualized on the basis of the patient’s treatment history and other clinical characteristics. Pharmacists perform many essential roles in the management of acute pain, including patient education, ensuring the accuracy and safety of prescribed medications, and performing regular assessment of the efficacy and safety of opioid therapy. (Adv Stud Pharm. 2008;5(2):52-57)
Taking biological structure communications into the third dimension.

In this issue of Acta Crystallographica F, Structural Biology Communications, Firth et al. (2019) present a text-mining tool for automatic protein-residue annotation in published papers. The tool, called pyresid, searches the text of an article for references to amino acids, then identifies the relevant protein and links that amino acid reference in the text to the residue in the associated PDB or mmcif file(s). In doing so, it enables the reader, at the touch of a button, to jump to the relevant part of the 3D structure. By the time you read this, our developer, Simon Westrip, will have implemented an annotation system for all our Acta F articles that uses pyresid behind the scenes. For example, if you are reading this online, you can navigate to Mank et al. (2018), ‘Structure of aspartate -semialdehyde dehydrogenase from Francisella tularensis’ or to Molina et al. (2018), ‘Structure and stability of the human respiratory syncytial virus M2-1 RNAbinding core domain reveals a compact and cooperative folding unit’. Clicking on one of the highlighted amino acids in these articles will bring up a simple structure browser (based on 3Dmol.js; Rego & Koes, 2015), showing where the selected residue is in the 3D structure. Using the spanner icon, you can display the protein in cartoon format, stick format or ball-and-stick format. It will also allow you to hide or display water molecules and choose a white or black background. For display of the associated experimental electron density, you will need to open a specialized structure visualization program but this may be included in future versions if the annotations prove popular. ISSN 2053-230X
Efectividad del tratamiento con ondas de choque extracorpóreas en la epicondilitis humeral Effectiveness of the treatment with extracorporeal shock waves in the humeral epicondylitis.

Introduction: Lateral humeral epicondylitis is the most frequent injury of the elbow, this pathology sometime does not evolve favourably with medical treatments and physiotherapeutic conservatives, end up resorting to the surgical treatment. In the last 10-15 years with the appearance of the generators of extracorporeal shock waves, this pathology has found a solution alternative. The aim of this study is value the effectiveness and the security of this therapy, through bibliographical search. Material and method: For the accomplishment of this revision we have used an exhaustive search through different data bases, being the most excellent Medline and Cochrane Library and by means of a manual search in the libraries of Murcia, being in the one from the UCAM where they were greater number of articles. A table of inclusion criteria was made. Being used for the article selection, single accepting those that obtained a score of 3 or superior in the table. Results: after passing the criteria of selection, 29 articles has been obtained, which they were 9 revisions, 19 clinical tests and one series of cases. In the clinical tests and series of cases, the obtained results were 63% effective, 32% ineffective and 5% of doubtful. However in the revisions only were 33% effectives, 11% ineffective and 56% of doubtful. Also it is determined that the security depended on the correct application and a low dose of treatment. Conclusions: With the collected data we cannot consider that the therapy with extracorporeal shock waves is effective in this type of injury. Can be accepted, with a correct application and the suitable precautions that are a safe technique.
Successes and challenges in simulating the folding of large proteins

Computational simulations of protein folding can be used to interpret experimental folding results, to design new folding experiments, and to test the effects of mutations and small molecules on folding. However, whereas major experimental and computational progress has been made in understanding how small proteins fold, research on larger, multidomain proteins, which comprise the majority of proteins, is less advanced. Specifically, large proteins often fold via long-lived partially folded intermediates, whose structures, potentially toxic oligomerization, and interactions with cellular chaperones remain poorly understood. Molecular dynamics based folding simulations that rely on knowledge of the native structure can provide critical, detailed information on folding free energy landscapes, intermediates, and pathways. Further, increases in computational power and methodological advances have made folding simulations of large proteins practical and valuable. Here, using serpins that inhibit proteases as an example, we review native-centric methods for simulating the folding of large proteins. These synergistic approaches range from Gō and related structure-based models that can predict the effects of the native structure on folding to all-atom-based methods that include side-chain chemistry and can predict how disease-associated mutations may impact folding. The application of these computational approaches to serpins and other large proteins highlights the successes and limitations of current computational methods and underscores how computational results can be used to inform experiments. These powerful simulation approaches in combination with experiments can provide unique insights into how large proteins fold and misfold, expanding our ability to predict and manipulate protein folding.
The joy of balancers

Balancer chromosomes are multiply inverted and rearranged chromosomes that are widely used in Drosophila genetics. First described nearly 100 years ago, balancers are used extensively in stock maintenance and complex crosses. Recently, the complete molecular structures of several commonly used balancers were determined by whole-genome sequencing. This revealed a surprising amount of variation among balancers derived from a common progenitor, identified genes directly affected by inversion breakpoints, and cataloged mutations shared by balancers. These studies emphasized that it is important to choose the optimal balancer, because different inversions suppress meiotic recombination in different chromosomal regions. In this review, we provide a brief history of balancers in Drosophila, discuss how they are used today, and provide examples of unexpected recombination events involving balancers that can lead to stock breakdown.
Virtual Modeling of a Cleft Lip and Palate Patient

Aim: To demonstrate three-dimensional virtual modeling of a cleft lip and palate patient. Methodology: Traditional two-dimensional treatment planning modalities are often inadequate. Developing technology has enabled the virtual modeling of cleft lip and palate patients. Mimics software was used to demonstrate how to construct such a model. Conclusion: We are now able to model cleft lip and palate patients in three dimensions. How to cite this article: Karadede I, Adiguzel O, Ozer T, Bilgic F, Ozhal Izol R. Virtual Modeling of a Cleft Lip and Palate Patient. Int Dent Res 2012;2:43-47. Linguistic Revision: The English in this manuscript has been checked by at least two professional editors, both native speakers of English.
Inactivating Mutations in NPC1L1 and Protection from Coronary Heart Disease

Background Ezetimibe lowers plasma levels of low-density lipoprotein (LDL) cholesterol by inhibiting the activity of the Niemann–Pick C1-like 1 (NPC1L1) protein. However, whether such inhibition reduces the risk of coronary heart disease is not known. Human mutations that inactivate a gene encoding a drug target can mimic the action of an inhibitory drug and thus can be used to infer potential effects of that drug. Methods We sequenced the exons of NPC1L1 in 7364 patients with coronary heart disease and in 14,728 controls without such disease who were of European, African, or South Asian ancestry. We identified carriers of inactivating mutations (nonsense, splice-site, or frameshift mutations). In addition, we genotyped a specific inactivating mutation (p.Arg406X) in 22,590 patients with coronary heart disease and in 68,412 controls. We tested the association between the presence of an inactivating mutation and both plasma lipid levels and the risk of coronary heart disease. Results With sequencing, we identified 15 distinct NPC1L1 inactivating mutations; approximately 1 in every 650 persons was a heterozygous carrier for 1 of these mutations. Heterozygous carriers of NPC1L1 inactivating mutations had a mean LDL cholesterol level that was 12 mg per deciliter (0.31 mmol per liter) lower than that in noncarriers (P = 0.04). Carrier status was associated with a relative reduction of 53% in the risk of coronary heart disease (odds ratio for carriers, 0.47; 95% confidence interval, 0.25 to 0.87; P = 0.008). In total, only 11 of 29,954 patients with coronary heart disease had an inactivating mutation (carrier frequency, 0.04%) in contrast to 71 of 83,140 controls (carrier frequency, 0.09%). Conclusions Naturally occurring mutations that disrupt NPC1L1 function were found to be associated with reduced plasma LDL cholesterol levels and a reduced risk of coronary heart disease. (Funded by the National Institutes of Health and others.)
Using compositional principal component analysis to describe children's gut microbiota in relation to diet and body composition.

BACKGROUND Gut microbiota data obtained by DNA sequencing are complex and compositional because of large numbers of detectable taxa, and because microbiota characteristics are described in relative terms. Nutrition researchers use principal component analysis (PCA) to derive dietary patterns from food data. Although compositional PCA methods are not commonly used to describe patterns from complex microbiota data, this approach would be useful for identifying gut microbiota patterns associated with diet and body composition. OBJECTIVES To use compositional PCA to describe the principal components (PCs) of gut microbiota in 5-y-old children and explore associations between microbiota components, diet, and BMI z-score. METHODS A fecal sample was provided by 319 children aged 5 y. Their primary caregiver completed a validated 123-item quantitative FFQ. Body composition was determined using DXA, and a BMI z-score was calculated. Compositional PCA identified characterizing taxa and weightings for calculation of gut microbiota PC scores at the genus level, and was examined in relation to diet and body size. RESULTS Three gut microbiota PCs were found. PC1 (negative loadings on uncultured Christensenellaceae and Ruminococcaceae) was related to lower BMI z-scores and longer duration of breastfeeding (per month) (β = -0.14; 95% CI: -0.26, -0.02; and β = 0.02; 95% CI: 0.003, 0.34, respectively). PC2 (positive loadings on Fusicatenibacter and Bifidobacterium; negative loadings on Bacteroides) was associated with a lower intake of nuts, seeds, and legumes (β = -0.05 per gram; 95% CI: -0.09, -0.01). When adjusted for fiber intake, PC2 was also associated with higher BMI z-scores (β = 0.12; 95% CI: 0.01, 0.24). PC3 (positive loadings on Faecalibacterium, Eubacterium, and Roseburia) was associated with higher intakes of fiber (β = 0.02 per gram; 95% CI: 0.003, 0.04) and total nonstarch polysaccharides (β = 0.02 per gram; 95% CI: 0.003, 0.04). CONCLUSIONS Our results suggest that specific gut microbiota components determined using compositional PCA are associated with diet and BMI z-score.This trial was registered at clinicaltrials.gov as NCT00892983.
FGF23 and Phosphate–Cardiovascular Toxins in CKD

Elevated levels of fibroblast growth factor 23 (FGF23) and phosphate are highly associated with increased cardiovascular disease and mortality in patients suffering from chronic kidney disease (CKD). As the kidney function declines, serum phosphate levels rise and subsequently induce the secretion of the phosphaturic hormone FGF23. In early stages of CKD, FGF23 prevents the increase of serum phosphate levels and thereby attenuates phosphate-induced vascular calcification, whereas in end-stage kidney disease, FGF23 fails to maintain phosphate homeostasis. Both hyperphosphatemia and elevated FGF23 levels promote the development of hypertension, vascular calcification, and left ventricular hypertrophy by distinct mechanisms. Therefore, FGF23 and phosphate are considered promising therapeutic targets to improve the cardiovascular outcome in CKD patients. Previous therapeutic strategies are based on dietary and pharmacological reduction of serum phosphate, and consequently FGF23 levels. However, clinical trials proving the effects on the cardiovascular outcome are lacking. Recent publications provide evidence for new promising therapeutic interventions, such as magnesium supplementation and direct targeting of phosphate and FGF receptors to prevent toxicity of FGF23 and hyperphosphatemia in CKD patients.
Cytocompatibility of Polyurethane foams as Biointegrable Matrices for the Preparation of Scaffolds for Bone Reconstruction

This work reports preliminary results on the development of biointegrable scaffolds, composed of biostable 3D polymer matrices and bioabsorbable inorganic salts, to be used for cell anchorage in bone regeneration. Three crosslinked polyurethane foams (PUFs), prepared by one-step bulk polymerisation from a polyether-polyol mixture, polymeric MDI and water as expanding agent, were tested for their ability to promote adhesion and growth of bone-derived cells. The open porosity of these foams ranged from 16 to 31% with an average pore size of 470÷600 μm, compressive strength (at 10% ε) of 0.28÷0.38 MPa and elastic moduli of 4.88÷6.61 MPa. The human osteosarcoma line Saos-2, and primary cultures of normal human articular chondrocytes and bone marrow-derived (HBM) stromal cells were used for in vitro cytocompatibility tests. For cell adhesion and proliferation analysis, DNA synthesis was evaluated by H-thymidine uptake. Osteoblastic differentiation of Saos-2 adherent cells was determined by measuring the enzymatic activity of alkaline phosphatase (ALP). All cell types were able to adhere to all tested PUFs and to synthesize DNA. At 48 hr culture, HBM stromal cells showed the maximal rate of adhesion with the highest rate of proliferation onto PUFs with the largest pore size, whereas both chondrocytes and Saos-2 appeared to adhere preferentially onto foams exhibiting the highest percentage of open porosity. Up to 8 days in culture Saos-2 cells were able to proliferate into all PUFs, with a time-dependent increase of DNA synthesis and ALP activity. At SEM, the morphology of cells adherent to PUF pores was spread with cytoplasmatic extroflessions, indicating a good metabolic
Psychosocial Risk Factors Among Telephone Service Workers: A Study of the Interaction between Customer and Worker

Many activities in the telephone industry involve interaction with customers, including both traditional (for example, client assistance) and emerging services (product sales). Interaction with customers has been reported to cause stress in workers. The study was initiated as a consequence of changes in dialing of long-distance numbers. The main sources of stress among workers in Traffic and Customer Services Departments were analyzed, together with the resulting psychological distress and other health symptoms. Information was gathered through semi-structured interviews and a questionnaire containing the Spanish version of the Job Content Questionnaire, as well as psychological strain and health symptoms items. Questions developed specifically for this study concerned emotional demands, client interactions, and mechanisms used to deal with violent or unpleasant interactions. Workers received valuable information from the study that empowered them to demand improved working conditions.
Interaction between Angiotensin II and BDNF in Modulating Sympathetic Nerve Activity

INTERACTION BETWEEN ANGIOTENSIN II AND BDNF IN MODULATING SYMPATHETIC NERVE ACTIVITY: Bryan K. Becker, Ph.D. University of Nebraska Medical Center, 2015 Supervisor: Irving H. Zucker, Ph.D. Over activation of the sympathetic nervous system is prevalent in many forms of cardiovascular disease such as chronic heart failure (CHF) and hypertension. Although increased neuronal renin-angiotensin system activity in presympathetic neurons has been well implicated in mediating this sympatho-excitation, many of the neuronal effects of angiotensin II (Ang II) signaling remain poorly understood. One particular mechanism of Ang II-mediated increases in presympathetic neuronal activity is through reductions in voltage-gated K currents. Another pathway that has profound effects on neuronal K currents and that has been previously implicated in Ang II-signaling is brain-derived neurotrophic factor (BDNF) activity through its receptor tyrosine kinase B (TrkB). Therefore, we hypothesized that BDNF/TrkB signaling is an important mediator of the neuronal effects of Ang II in modulating voltage-gated K currents and autonomic dysfunction in cardiovascular disease states such as CHF and hypertension. We employed cell culture and whole-animal models to explore this hypothesis and utilized electrophysiological, molecular, and in vivo physiological techniques. Patch-clamp studies demonstrated that BDNF is involved in Ang II-induced reductions to K currents. Further in-vivo experiments found that overexpression of Kv4.3 into the rostral ventrolateral medulla attenuates the increase in sympathetic nerve activity of rats post-myocardial infarction. Baroreflex dysfunction is common in CHF, and desensitization of central neuronal areas such as the nucleus tractus solitarius (NTS) can mediate this dysfunction. We therefore hypothesized that changes in BDNF/TrkB signaling in the NTS mediated baroreflex dysfunction in CHF. Blocking TrkB with ANA-12 in the NTS blunted baroreflex sensitivity in sham rats but had little effect on the already blunted baroreflex sensitivity of CHF rats. TrkB expression was reduced in CHF rats, implicating reduced BDNF/TrkB signaling
A MIMO-SAR Tomography Algorithm Based on Fully-Polarimetric Data

A fully-polarimetric unitary multiple signal classification (UMUSIC) tomography algorithm is proposed, which can be used for acquiring high-resolution three-dimensional (3D) imagery, in a polarimetric multiple-input multiple-output synthetic aperture radar (MIMO-SAR) with a small number of baselines. In terms of the elevation resolution, UMUSIC provides an improvement over standard MUSIC by utilizing the conjugate of the complex sample data and converting the complex covariance matrix into a real matrix. The combination of UMUSIC and fully-polarimetric data permits a further reduction of the noise of the sample covariance matrix, which is obtained through pixel averaging of multiple two-dimensional (2D) images. Considering the consistency of four polarizations, this algorithm not only makes scattering centers have the same estimated height in four polarizations, but it also improves the estimation accuracy. Simulation results show that this algorithm outperforms the popular distributed compressed sensing (DCS). Image processing of measured data of an aircraft model using a multiple-input multiple-output synthetic aperture radar (MIMO-SAR) with six baselines is presented to validate the proposed algorithm.