Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of the Molecular Defects in Rab27a, Caused by RAB27A Missense Mutations Found in Patients with Griscelli Syndrome*

Rab27a plays a pivotal role in the transport of melanosomes to dendrite tips of melanocytes and mutations in RAB27A, which impair melanosome transport cause the pigmentary dilution and the immune deficiency found in several patients with Griscelli syndrome (GS). Interestingly, three GS patients present single homozygous missense mutations in RAB27A, leading to W73G, L130P, and A152P transitions that affect highly conserved residues among Rab proteins. However, the functional consequences of these mutations have not been studied. In the present report, we evaluated the effect of overexpression of these mutants on melanosome, melanophilin, and myosin-Va localization in B16 melanoma cells. Then we studied several key parameters for Rab27a function, including GTP binding and interaction with melanophilin/myosin-Va complex, which links melanosomes to the actin network. Our results showed that Rab27a-L130P cannot bind GTP, does not interact with melanophilin, and consequently cannot allow melanosome transport on the actin filaments. Interestingly, Rab27a-W73G binds GTP but does not interact with melanophilin. Thus, Rab27a-W73G cannot support the actin-dependent melanosome transport. Finally, Rab27a-A152P binds both GTP and melanophilin. However, Rab27a-A152P does not allow melanosome transport and acts as a dominant negative mutant, because its overexpression, in B16 melanoma cells, mimics a GS phenotype. Hence, the interaction of Rab27a with melanophilin/myosin-Va is not sufficient to ensure a correct melanosome transport. Our results pointed to an unexpected complexity of Rab27a function and open the way to the search for new Rab27a effectors or regulators that control the transport of Rab27a-dependent vesicles.
The influence of tobacco smoking on the outcomes achieved by root-coverage procedures: a systematic review.

BACKGROUND The authors conducted a systematic review to evaluate the effect of smoking on the clinical outcomes achieved by periodontal plastic surgery procedures in the treatment of recession-type defects. TYPES OF STUDIES REVIEWED The authors performed an electronic search on MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomized controlled clinical trials, controlled clinical trials and case series that involved at least six months' follow-up. They looked for studies published through June 2008 that compared the outcome measures achieved by smokers and nonsmokers after they underwent periodontal plastic surgery procedures for treatment of gingival recession. RESULTS From a total of 632 references, the authors considered seven studies to be relevant. The meta-analysis indicated a statistically significant greater reduction in gingival recession (P < .001) and gain in clinical attachment level (P < .001) for nonsmokers when compared with smokers whose gingival recession was treated with subepithelial connective-tissue grafts. Additionally, nonsmokers exhibited significantly more sites with complete root coverage than did smokers (P = .001). For coronally advanced flaps, differences between the groups were not significant. CLINICAL IMPLICATIONS The results of this review show that smoking may negatively influence gingival recession reduction and clinical attachment level gain. Additionally, smokers may exhibit fewer sites with complete root coverage.
Isolation and characterization of novel iron-oxidizing bacteria that grow at circumneutral pH

A gel-stabilized gradient method that employed opposing gradients of Fe2+ and O2 was used to isolate and characterize two new Fe-oxidizing bacteria from a neutral pH, Fe(2+)-containing groundwater in Michigan. Two separate enrichment cultures were obtained, and in each the cells grew in a distinct, rust-colored band in the gel at the oxic-anoxic interface. The cells were tightly associated with the ferric hydroxides. Repeated serial dilutions of both enrichments resulted in the isolation of two axenic strains, ES-1 and ES-2. The cultures were judged pure based on (i) growth from single colonies in tubes at dilutions of 10(-7) (ES-2) (ES-2) and 10(-8) (ES-1); (ii) uniform cell morphologies, i.e., ES-1 was a motile long thin, bent, or S-shaped rod and ES-2 was a shorter curved rod; and (iii) no growth on a heterotrophic medium. Strain ES-1 grew to a density of 10(8) cells/ml on FeS with a doubling time of 8 h. Strain ES-2 grew to a density of 5 x 10(7) cells/ml with a doubling time of 12.5 h. Both strains also grew on FeCO3. Neither strain grew without Fe2+, nor did they grow with glucose, pyruvate, acetate, Mn, or H2S as an electron donor. Studies with an oxygen microelectrode revealed that both strains grew at the oxic-anoxic interface of the gradients and tracked the O2 minima when subjected to higher O2 concentrations, suggesting they are microaerobes. Phylogenetically the two strains formed a novel lineage within the gamma Proteobacteria. They were very closely related to each other and were equally closely related to PVB OTU 1, a phylotype obtained from an iron-rich hydrothermal vent system at the Loihi Seamount in the Pacific Ocean, and SPB OTU 1, a phylotype obtained from permafrost soil in Siberia. Their closest cultivated relative was Stenotrophomonas maltophilia. In total, this evidence suggests ES-1 and ES-2 are members of a previously untapped group of putatively lithotrophic, unicellular iron-oxidizing bacteria.
Enrichissement de lexiques sémantiques approvisionnés par les foules : le système WISIGOTH appliqué à Wiktionary [Enrichment of crowdsourced semantic networks: The WISIGOTH system applied to Wiktionary]

Semantic lexical resources are a mainstay of various NLP applications. However, comprehensive and reliable resources rarely exist or are often not freely available. We discuss in this paper the context of lexical resources building and the problems of evaluation. We present Wiktionary, a freely available and collaboratively built multilingual dictionary and we propose a semi-automatic approach based on random walks for enriching its synonymy network, which uses endogenous and exogenous data. We then propose a validation "by crowds". Finally, we present an implementation of this system called WISIGOTH.
Case series of idiopathic membranous nephropathy with long-term beneficial effects of ACTH peptide 1-24.

BACKGROUND In patients with idiopathic membranous nephropathy (IMN), immunosuppressive therapy is usually considered when severe nephrotic syndrome or risk for progressive renal failure exist. Recently, several studies showing beneficial effects of synthetic adrenocorticotropic hormone (ACTH) under such circumstances have been published. The objective of the present case series was to evaluate long-term ACTH effects on proteinuria and renal function. METHODS Four patients with biopsy-proven membranous nephropathy and nephrotic syndrome were enrolled (median age 50 years (range 38 - 61), median GFR 39.5 ml/min (range 20 - 62), median proteinuria 9.6 g/d (range 6.0 - 20.0). Prior immunosuppressive treatment regimens included steroids, cyclosporine A, cyclophosphamide, mycophenolate mofetil or azathioprine. The patients received a synthetic ACTH analogue intramuscularly for a median duration of 8 months (range 3 - 24). ACTH dosage was adjusted according to side effects between 0.25 and 2.25 mg/week. Follow-up lasted between 24 and 82 months after therapy initiation. RESULTS All 4 patients exhibited partial (n = 2) or complete (n = 2) remissions of their nephrotic syndrome within the first year. After discontinuation of ACTH therapy, proteinuria remained low in 3 of 4 cases, whereas 1 patient exhibited undulating proteinuria. Glomerular function (as assessed by glomerular filtration rate, GFR) was maintained in all patients. Side effects were minor and included weight gain, elevated blood pressure and hyperglycemia. CONCLUSION In all 4 cases with IMN, ACTH treatment induced a lasting disease remission with relatively few side effects.
Effects of vascular endothelial cells on osteogenic differentiation of noncontact co-cultured periodontal ligament stem cells under hypoxia.

BACKGROUND AND OBJECTIVE During periodontitis or orthodontic tooth movement, the periodontal vasculature is severely impaired by chronic inflammation or excessive mechanical force. This leads to a hypoxic microenvironment of the periodontal cells and enhances the expression of various cytokines and growth factors that may regulate angiogenesis and alveolar bone remodeling. However, the role of hypoxia in regulating the communication between endothelial cells (ECs) and osteoblast progenitors during the remodeling and repair of periodontal tissue is still poorly defined. The aim of this study was to investigate the effects of vascular ECs on osteogenic differentiation, mineralization and the paracrine function of noncontact co-cultured periodontal ligament stem cells (PDLSCs) under hypoxia, and further reveal the involvement of MEK/ERK and p38 MAPK pathways in the process. MATERIAL AND METHODS First, PDLSCs were obtained and a noncontact co-culture system of PDLSCs and human umbilical vein endothelial cells was established. Second, the effects of different time-periods of hypoxia (2% O(2) ) on the osteogenic potential, mineralization and paracrine function of co-cultured PDLSCs were investigated. Third, ERK1/2 and p38 MAPK activities of PDLSCs under hypoxia were measured by western blotting. Finally, we employed specific MAPK inhibitors (PD98059 and SB20350) to investigate the involvement of ERK1/2 and p38 MAPK in PDLSC osteogenesis under hypoxia. RESULTS We observed further increased osteogenic differentiation of co-cultured PDLSCs, manifested by markedly enhanced alkaline phosphatase (ALP) activity and prostaglandin E(2) (PGE(2)) levels, vascular endothelial growth factor (VEGF) release, runt-related transcription factor 2 (Runx2) and Sp7 transcriptional and protein levels and mineralized nodule formation, compared with PDLSCs cultured alone. ERK1/2 was phosphorylated in a rapid but transient manner, whereas p38 MAPK was activated in a slow and sustained way under hypoxia. Furthermore, hypoxia-stimulated transcription and expression of osteogenic regulators (hypoxia-inducible factor-1α, ALP, Runx2, Sp7, PGE(2) and VEGF) were also inhibited by PD98059 and SB203580 to different degrees. CONCLUSION Further increased osteogenic differentiation and mineralization of co-cultured PDLSCs under hypoxia were regulated by MEK/ERK and p38 MAPK pathways. And the ECs-mediated paracrine of PGE(2) and VEGF may facilitate the unidirectional PDLSC-EC communication and promote PDLSCs osteogenesis.
Clinical use of indices determined non-invasively from the radial and carotid pressure waveforms

ObjectiveTo evaluate the clinical use of radial and carotid artery applanation tonometry as an independent supplement to cuff sphygmomanometry. MethodsIn 44 patients, radial and carotid tonometric pressure recordings were taken at short intervals apart by two persons who had prolonged experience with both. Comparisons were made between directly recorded radial and carotid waveforms and between aortic waves synthesized from both, using SphygmoCor. Focus was on waveform features: time intervals between wavefoot and incisura, denoting ejection duration, between wavefoot and first systolic peak or shoulder (T1), and augmentation index – the rise in pressure from this point to systolic peak divided by pulse pressure. ResultsNo patient had discomfort with radial tonometry, whereas many found carotid tonometry uncomfortable. Beat-to-beat variability was lower for the radial than carotid site. The device's operator ‘quality index’ was achieved for 78% of radial waveforms but just 20% of carotid waveforms (P<0.05). Interobserver variability was lower for all indices derived from radial, cf. carotid, waveforms. For the two observers combined, there was no difference between aortic indices determined from carotid and radial sites except for T1 (radial-derived 117±17 ms, cf. carotid-derived 103±17 ms, P<0.05), but this did not influence the value of augmentation index (radial-derived 26±13%, cf. carotid-derived 28±14%, P=NS). ConclusionThe present study conforms with most published results, and indicates superiority of radial to carotid tonometry in clinical practice.
Screening for thoracolumbar spinal injuries in blunt trauma: An Eastern Association for the Surgery of Trauma practice management guideline

BACKGROUND Thoracolumbar spine (TLS) injuries have an incidence rate of 5% in blunt trauma patients. The Eastern Association for the Surgery of Trauma published Practice Management Guidelines for the Screening of Thoracolumbar Spine Fracture in 2007. The Practice Management Guidelines Committee was assembled to reevaluate the literature. METHODS A search of the United States National Library of Medicine and the National Institutes of Health database was performed using MEDLINE through PubMed (www.pubmed.gov). The search retrieved English-language articles from March 2005 to December 2011 that referenced traumatic TLS injuries and fractures. The questions posed were the following: (1) What is the appropriate imaging modality to screen patients for TLS injuries? (2) Which trauma patients require radiographic screening for TLS injuries? (3)Does a patient who is awake and alert without distracting injuries require radiologic workup to rule out TLS injuries? RESULTS Thirty-seven articles that referenced traumatic TLS injuries in association with screening published between March 2005 and December 2011 were collected and disseminated to the committee. Twelve were found to be relevant. Nine publications from the previous 2006 guidelines were reviewed and referenced to create and validate the updated guidelines. CONCLUSION Practice patterns have changed regarding screening blunt trauma patients for TLS injuries. Software reformatted multidetector computed tomographic scans are more sensitive and accurate than plain films. Multidetector computed tomographic scans have become the screening modality of choice and the criterion standard in screening for TLS injuries. The literature supports a Level 1 recommendation to validate this based on a preponderance of Class II data. Patients without altered mentation or significant mechanism may be excluded by clinical examination without imaging. Patients with gross neurologic deficits or concerning clinical examination findings with negative imaging should receive a magnetic resonance imaging expediently, and the spine service should be consulted.
The Context & Clinical Evidence for Common Nursing Practices During Labor

The purpose of this article is to review the context and current evidence for common nursing care practices during labor and birth. Although many nursing interventions during labor and birth are based on physician orders, there are a number of care processes that are mainly within the realm of nursing practice. In many cases, particularly in community hospitals, routine physician orders for intrapartum care provide wide latitude for nurses in how they ultimately carry out those orders. An important consideration of common nursing practices during labor is the context or practice model in which those practices occur. Nursing practice is not the same in all clinical environments. Intrapartum nursing practice consists of an assortment of different roles depending on the circumstances, hospital setting, and context in which it takes place. A variety of intrapartum nursing practice models have evolved as a result and in response to the range of sizes, locations, and provider practice styles found in hospitals providing obstetric services. A summary of intrapartum nursing models is presented. The evidence is reviewed for the three most common clinical practices for which nurses have primary responsibility in most settings and that comprise the majority of their time in caring for women during labor: (1) maternal-fetal assessment, (2) management of oxytocin infusions, and (3) second-stage care. Evidence exists for these nursing interventions that can be used to promote maternal-fetal well-being, minimize risk, and enhance patient safety.
Electrophysiological Actions of N‐(2,6‐Dimethylphenyl)‐8‐Pyrrolizidine‐Acetamide Hydrochoride Hemihydrate (SUN 1165), a New Antiarrhythmic Agent

Summary: The electrophysiological actions of SUN 1165 on isolated guinea pig atrial and papillary muscles, canine Purkinje fibers, and rabbit sinoatrial node were studied using standard microelectrode techniques. SUN 1165 in low (10-7 g/ml) concentration had little effect on any of the action potential parameters measured. Intermediate (10-6 g/ml) concentration of the compound shortened the duration of action potential of canine Purkinje fibers and increased ratio of the effective refractory period to the duration of action potential at 90% repolarization in guinea pig atrial muscles. At high (10-5 g/ml) concentration, the compound reduced the maximum rate of rise of phase 0 in guinea pig atrial, papillary muscles, and canine Purkinje fibers, though the change in the latter was not statistically significant, and also decreased the action potential amplitude in guinea pig atrial muscles and canine Purkinje fibers. At all concentrations (10-7-10-5 g/ml) tested, the compound exerted little effect both on spontaneous action potentials in rabbit sinoatrial node cells and on Ca2+ -mediated slow responses in partially depolarized guinea pig papillary muscles. These results indicate that SUN 1165 may selectively inhibit cardiac sodium channels and is likely to be of value in correcting not only ventricular but also supraventricular tachyarrhythmias.
Binding and the effect of the red kidney bean lectin, phytohaemagglutinin, in the gastrointestinal tract of suckling rats

Enteral exposure of suckling rats to phytohaemagglutinin (PHA) has been shown to induce growth and precocious functional maturation of the gastrointestinal tract. The aim of the present study was to explore the mechanism of this action. Suckling rats, 14d old, were fed a single dose of PHA (0·05mg/g body weight) or saline. The binding of PHA to the gut epithelium and its effect on the morphology and functional properties of the gut and pancreas were studied up to 3d after treatment. Initially, at 1–24h, the PHA bound along the gut mucosal lining, resulting in disturbed gut morphology with villi shortening and rapid decreases in disaccharidase activities and macromolecular absorption capacity. During a later phase, between 1 and 3d, the PHA binding had declined, and an uptake by enterocytes was observed. An increase in crypt cell proliferation and gut growth became evident during this period, together with a functional maturation, as indicated by increases in disaccharidase (maltase and sucrase) activities and the low macromolecular absorption capacity. Pancreas growth also increased, as did its content of digestive enzymes. We conclude that enteral exposure to PHA in suckling rats temporarily causes mucosal disarrangement and functional impediment of the gut, which may be explained by binding to and disruption of the gut mucosa and a two-fold increase in the plasma corticosterone concentration. These findings may lead to a better understanding of the role of diet in gastrointestinal maturation and may constitute a basis for the treatment of mammals having an immature gut.
The relationship, responses, and reforms pertaining to gun violence and mental illness in the United States

The United States faces an ever-growing public health concern of gun violence, having the highest rate of homicide by firearm use among Western countries. American leaders on this subject have debated for many years on how to address this issue. Such debate, in turn, has brought up the concern of the mentally ill in possession of firearms, especially in light of mass shootings. The goal of this thesis is to determine the existence of a relationship between gun violence and mental illness. The significance of discerning this relationship is multi-faceted in that gun violence psychologically traumatizes its victims and also has been linked with mental illnesses in a stigmatizing manner, thanks to the spotlight on mass shootings by the media. Through literature analysis of the behaviors of those with schizophrenia, bipolar disorder, and alcohol abuse, it was determined that, although increasing a person’s chances for experiencing at-risk behaviors for violence, intrinsic mental disorders such as schizophrenia and bipolar disorder are not statistically associated with gun violence. In fact, not only has it been reported that very few firearm-related acts of violence are linked with those with mental illnesses, but
Electromechanical studies on the inotropic effects of acetylstrophanthidin in ventricular muscle.

Three phases in the inotropic response of acetyl strophanthidin (AcS) on the electromechnical activity of the frog ventricular myocardium were identified and studied using a single sucrose voltage‐clamp technique and other conventional electrophysiological methods. 2. the positive inotropic response of the drug was accompanied by a shift in tension‐voltage relation, so that more tension developed with every depolarization step above the mechanical threshold (‐50mV). Only at higher drug concentrations or with long exposure times did the mechanical threshold shift to more negative membrane potentials (‐60 to‐70 mV). 3. In tetrodotoxin‐treated muscles AcS produced marked potentiation of twitch tension and an appropriate shift in the tension‐voltage relation. 4. the positive inotropic response of the drug was not related to the magnitude of the direction of the fast or slow Na current. 5. in tetrodotoxin‐treated ventricular strips the direction or the magnitude of the secondary inward current (ICa or INa) were not related to the inotropic effect of AcS. 6. AcS shortens the action potential markedly during the later stages of its positive inotropic response. When Ca2+ is omitted from the bathing solution AcS not only fails to shorten the action potential, but often prolongs it. 7. The shortening of the action potential in the presence of AcS is accompanied by an increase in the "instantaneous" membrane conductance both at rest and during the time course of the plateau. 8. The decline in the positive inotropic response of the drug was accompanied by the shortening of the action potential. Electrical or chemical prolongation of the action potential restored the full positive inotropic response if the membrane had not depolarized. 9. Membrane depolarization and the development of diastolic tension always occurred at later stages of drug action. Elevation of [Mg+2]degrees to 5 or 10 mM prevented or suppressed the membrane depolarization and the diastolic tension. 10. KCl‐induced contractures were potentiated throughout the duration of drug exposure. The tonic component of the contracture tension was markedly elevated especially at later stages of drug action. 11. The experimental evidence suggests that no unitary mechanism could account for multiple actions of acetyl strophanthidin. However, the contributions of the Na pump, the Ca+2 sequestering system, and the K‐efflux system to the various stages of drug action are discussed.