Miracle-dz/UniFAR-FTUs huggingface dataset:
Caveolin-2 Localizes to the Golgi Complex but Redistributes to Plasma Membrane, Caveolae, and Rafts when Co-expressed with Caveolin-1*

We have characterized comparatively the subcellular distributions of caveolins-1 and -2, their interactions and their roles in caveolar formation in polarized epithelial cells. In Fischer rat thyroid (FRT) cells, which express low levels of caveolin-2 and no caveolin-1, caveolin-2 localizes exclusively to the Golgi complex but is partially redistributed to the plasma membrane upon co-expression of caveolin-1 by transfection or by adenovirus-mediated transduction. In Madin-Darby canine kidney (MDCK) cells, which constitutively express both caveolin-1 and -2, caveolin-2 localized to both the Golgi complex and to the plasma membrane, where it co-distributed with caveolin-1 in flat patches and in caveolae. In FRT cells, endogenous or overexpressed caveolin-2 did not associate with low density Triton insoluble membranes that floated in sucrose density gradients but was recruited to these membranes when co-expressed together with caveolin-1. In MDCK cells, both caveolin-1 and caveolin-2 associated with low density Triton-insoluble membranes. In FRT cells, transfection of caveolin-1 promoted the assembly of plasma membrane caveolae that localized preferentially (over 99%) to the basolateral surface, like constitutive caveolae of MDCK cells. In contrast, as expected from its intracellular distribution, endogenous or overexpressed caveolin-2 did not promote the assembly of caveolae; rather, it appeared to promote the assembly of intracellular vesicles in the peri-Golgi area. The data reported here demonstrate that caveolin-1 and -2 have different and complementary subcellular localizations and functional properties in polarized epithelial cells and suggest that the two proteins co-operate to carry out specific as yet unknown tasks between the Golgi complex and the cell surface.
Craniofacial structure in Marfan syndrome: A cephalometric study

Marfan syndrome (MFS) is a connective tissue disorder with autosomal dominant inheritance. Mutations in the FBN1 gene cause deficient processing of fibrillin‐1, the main constituent of extracellular microfibrils, affecting tissues displaying elastic properties. Clinical manifestations are widespread and involve the skeletal, ocular, cardiovascular and pulmonary systems, skin and integumentum, and dura. A highly arched palate and retrognathia have been assigned to the symptoms with minor diagnostic specificity, although epidemiological data on prevalence are lacking yet. Twenty‐six patients with MFS (n = 26) were studied for craniofacial characteristics using cephalometric measurements on lateral cranial radiographs. The purposes of this study were (1) to compare cephalometric variables of MFS group with age‐ and sex‐matched population norms, and (2) to assess differences in palatal vault dimensions among adult MFS (n = 17) and matched controls (n = 32) by means of cephalometric measurements. Significant differences with population norms were found in the structures of the cranial base, the maxillary complex, the mandible body, and the relations of the jaws with respect to the cranial base and to each other. Palatal height and palatal length were significantly larger in MFS, and were significantly correlated to each other and to the height of the maxillo‐alveolar processus. The present data disprove in part previously reported findings, possibly due to biased patient selection in these studies or demographic differences. However, a strong correlation was found between maxillary/mandibular retrognathia, long face, highly arched palate, and MFS. A combination of both intrinsic genetic factors and environmental factors is suggested as a possible explanation for specific morphogenetic aspects of the craniofacial complex in MFS. © 2004 Wiley‐Liss, Inc.
Pro: Should we correct vitamin D deficiency/insufficiency in chronic kidney disease patients with inactive forms of vitamin D or just treat them with active vitamin D forms?

Evidence for the usefulness of using vitamin D to treat 'renal bone disease' is now nearly six decades old. In regular clinical practice, however, it is more like three decades, at most, that we have routinely been using vitamin D to try to prevent, or reverse, the impact of hyperparathyroidism on the skeleton of patients with chronic kidney disease (CKD). The practice has been in the main to use high doses of synthetic vitamin D compounds, not naturally occurring ones. However, the pharmacological impacts of the different vitamin D species and of their different modes, and styles of administration cannot be assumed to be uniform across the spectrum. It is disappointingly true to say that even in 2016 there is a remarkable paucity of evidence concerning the clinical benefits of vitamin D supplementation to treat vitamin D insufficiency in patients with stage 3b-5 CKD. This is even more so if we consider the non-dialysis population. While there are a number of studies that report the impact of vitamin D supplementation on serum vitamin D concentrations (unsurprisingly, usually reporting an increase), and some variable evidence of parathyroid hormone concentration suppression, there has been much less focus on hard or semi-rigid clinical end point analysis (e.g. fractures, hospitalizations and overall mortality). Now, in 2016, with the practice pattern changes of first widespread clinical use of vitamin D and second widespread supplementation of cholecalciferol or ergocalciferol by patients (alone, or as multivitamins), it is now, in my view, next to impossible to run a placebo-controlled trial over a decent period of time, especially one which involved clinically meaningful (fractures, hospitalisation, parathyroidectomy, death) end-points. In this challenging situation, we need to ask what it is we are trying to achieve here, and how best to balance potential benefits with potential harm.
In Vivo Analysis of Importin α Proteins Reveals Cellular Proliferation Inhibition and Substrate Specificity

ABSTRACT The “classical” nuclear import pathway depends on importins α and β. Humans have only one importin β, while six α importins have been described. Whether or not distinct α importins are essential for specific import pathways in living human cells is unclear. We used RNA interference technology to specifically down-regulate the expression of ubiquitously expressed human α importins in HeLa cells. Down-regulation of importins α3, α5, α7, and β strongly inhibited HeLa cell proliferation, while down-regulation of importins α1 and α4 had only a minor effect or no effect. Nucleoplasmin import was not prevented by down-regulation of any α importin, indicating that the importin α/β pathway was generally not affected. In contrast, importin α3 or α5 down-regulation specifically inhibited the nuclear import of the Ran guanine nucleotide exchange factor, RCC1. Coinjection of recombinant α importins and RCC1 into down-regulated cells demonstrated that these transport defects were specifically caused by the limited availability of importin α3 in both cases. Thus, importin α3 is the only α importin responsible for the classical nuclear import of RCC1 in living cells.
Imposing limits on autonomous systems

Abstract Our present era is witnessing the genesis of a sea-change in the way that advanced technologies operate. Amongst this burgeoning wave of untrammelled automation there is now beginning to arise a cadre of ever-more independent, autonomous systems. The degree of interaction between these latter systems with any form of human controller is becoming progressively more diminished and remote; and this perhaps necessarily so. Here, I advocate for human-centred and human favouring constraints to be designed, programmed, promulgated and imposed upon these nascent forms of independent entity. I am not sanguine about the collective response of modern society to this call. Nevertheless, the warning must be voiced and the issue debated, especially among those who most look to mediate between people and technology. Practitioner Summary: Practitioners are witnessing the penetration of progressively more independent technical orthotics into virtually all systems’ operations. This work enjoins them to advocate for sentient, rational and mindful human-centred approaches towards such innovations. Practitioners need to place user-centred concerns above either the technical or the financial imperatives which motivate this line of progress.
Measuring subclinical atherosclerosis: is homocysteine relevant?

Abstract Objectives: We systematically reviewed published studies looking at the relationship between total serum homocysteine (tHcy) and subclinical markers of atherosclerosis, such as carotid intimal-medial thickness (C-IMT), coronary artery calcium (CAC) and ankle-brachial index (ABI) in asymptomatic individuals. We analyzed these studies to examine this relationship as well as to guide future avenues of investigation by identifying studies that will help in the inclusion of tHcy levels in current guidelines on atherosclerotic disease management. Background: tHcy has been known to be associated with clinically evident atherosclerotic disease. However, tHcy is not incorporated in current guidelines for diagnosis of subclinical disease in high-risk asymptomatic individuals. Methods: We searched online databases (e.g., PUBMED, MEDLINE) for published articles assessing the relationship between tHcy and C-IMT, CAC and ABI. We limited the studies to asymptomatic populations, and excluded any study including symptomatic patients or individuals with a history of coronary, peripheral or cerebrovascular disease. Results: A systemic review of 19 articles revealed a significant association between elevated levels of tHcy and subclinical markers of atherosclerosis in asymptomatic individuals in most studies. Mean tHcy levels were consistently found to be higher in men compared to women. A total of 12 studies showed a significant association between tHcy and other risk markers of atherosclerosis, even after adjusting for age, sex and conventional risk factors. There were seven studies in unique populations that showed no significant relationship. We also observed that studies lowering baseline tHcy levels did not lead to an improvement in C-IMT, CAC or ABI scores. This might indicate that tHcy has a stronger role as a marker of atherosclerotic disease than as a risk factor for the same. Conclusions: Based on our review, we conclude that there is a significant association between the subclinical atherosclerotic process and tHcy, and it shows potential as a cheap marker for risk stratification of asymptomatic patients. However, future studies further elucidating this association and elaborating the exact role of tHcy in the atherosclerotic disease process are required. The results of these studies suggest the incorporation of plasma tHcy levels in future risk reduction protocols for identification of individuals at higher risk of atherosclerotic events, and thus to categorize them for more aggressive treatment with established preventive and therapeutic measures. Clin Chem Lab Med 2007;45:1667–77.
Performance Analysis of a Greenhouse Fan-Pad Cooling System: Gradients of Horizontal Temperature and Relative Humidity

Fan-Pad sogutma sistemi calisirken sera boyunca olusan sicaklik ve bagil nem degisimleri ve sogutma sistemi performans parametrelerini saptamak icin deneysel bir calisma yapilmistir. Calismada olcumler yedi farkli noktaya yerlestirilen sensorler ve tasinabilir olcum cihazlari kullanilarak gerceklestirilmistir. Bu amacla, bes dijital sicaklik-nem sensoru ve iki gunes isinim sensoru kullanilmistir. Sensorlerden ikisi sera disina, bir gunes isinim sensoru bitki ortusu ustune, dort sicaklik-nem sensoru sera boyunca bitki ortusu icine yerlestirilmistir. Dort sensorun yerlesimi Pad ve Fan arasinda tanimlanmis konumlara gore yapilmistir. Elde edilen deney sonuclarina gore, Pad tarafindan fan tarafina sera boyunca homojen olmayan sicaklik degisimleri, ancak transpirasyon nedeniyle yaklasik homojen kalan bagil nem degisimleri gozlemlenmistir. Sogutma sistemi kapali oldugu zaman, havanin 32 °C ve % 25 oldugu kosullarda, sera icinde Pad tarafindan fan tarafina saatlik ortalama sicaklik ve bagil nem degerleri sirasiyla 30–33 °C ve % 30–% 47 arasinda degismistir. Fan-Pad sistemi calistirilip kararli sogutma saglandiktan sonra, sera boyunca saatlik ortalama sicaklik ve bagil nem degerleri sirasiyla 20 – 27 °C ve % 50 –% 68, arasinda degismistir. Islak Pad yuzeyini gecerek yaklasik 0.8–0.9 m s-1 hava hizla seraya giren hava sicakligi dis hava sicakligindan 12–13 oC daha dusuk olmustur. Pad tarafindan fan tarafina sera boyunca hava sicakligi yaklasik 7 oC yukselmistir. Buharlasmali Fan-Pad sisteminin sogutma etkinligini hesaplamak icin psikrometrik hesaplama yontemi kullanilmistir. Hesaplama sonucuna gore, dis hava sicakliginin 31.4 oC oldugu kosullarda kararli sogutma saglandiktan sonra sera icindeki ortalama sicakligin 24.5 oC oldugu belirlenmistir. Fan-Pad sistemi icin hesaplanan saatlik ortalama sogutma etkisi ve sogutma etkinligi degerleri sirasiyla 6.96 oC ve % 76.8 olarak saptanmistir
Acute Sexual Assault: A Review

Abstract Acute sexual assault includes a broad spectrum of nonconsensual sexual activity. Care of victims of acute sexual assault can be challenging, especially given the significant potential psychological and legal ramifications of the event and subsequent medical care and forensic evidence collection. In some emergency department settings, utilization of sexual assault response teams and sexual assault nurse examiners has demonstrated that a systematic approach to these patients improves care. However, given that victims of acute sexual assault are likely to present for care in emergency departments where such teams do not exist, it is critical for the emergency medicine physician, pediatrician, and family physician to have knowledge of key aspects of history taking, the physical examination, evidence collection, and medical record documentation. This review of care of the victim of acute sexual assault will provide practitioners with the tools needed to effectively evaluate these patients.
Psychosocial Impact of Living with a Stuttering Disorder: Knowing Is Not Enough

Abstract Stuttering requires a multidimensional perspective given that, in recent years, researchers have shown the impact of the disorder to reach far beyond the surface components with demonstrated psychosocial and anxiety effects for the individual living with a stutter. This article explores the impact a stuttering disorder has on the individual (child, adolescent, and adult) and on their family members (siblings, parents, and partners). These experiences include behavioral and social difficulties, self-awareness, reactions to stuttering, communication difficulties in daily situations, and overall quality of life. The influence of stuttering on the most intimate relationships of the person who stutters is presented. An overview of stuttering across the life span is discussed in terms of stuttering in children and adolescents, and the significant levels of adverse impact as a result of living with a stutter are described. In addition, the impact that the stuttering disorder has on the parents and siblings of children who stutter is also detailed through significant findings pertaining to lack of attachment and trust between the young people and their parents. The responsibilities and demands on parents and siblings in the family context are highlighted. Focus is also placed on the experience of living with a person who stutters from the perspective of their life partner. Perceived quality of life is explored with unexpected differences recounted between the quality of life experienced by the adult who stutters and their partner's perceptions of this disorder. Finally, the potential for a novel Acceptance and Commitment Therapy for individuals who stutter is presented.
Kinetics of minority-carrier-enhanced dissociation of hydrogen-dopant complexes in semiconductors.

The kinetics of minority-carrier-enhanced dissociation of dopant-hydrogen complexes in semiconductors are quantitatively characterized with a new experimental technique. Its principal feature is the ability to control independently the width of the space-charge layer and the flux of minority carriers through the layer. The dissociation kinetics are formulated in terms of a phenomenological cross section for the capture of a minority carrier by a dopant-hydrogen complex. The method is demonstrated with hole-enhanced dissociation of the PH complex in silicon
Genotypes of Cryptosporidium spp. and Enterocytozoon bieneusi in Human Immunodeficiency Virus‐Infected Patients in Lagos, Nigeria

Molecular characterization of Cryptosporidium spp. and Enterocytozoon bieneusi has improved our understanding of the transmission of both organisms in humans. In this study, to infer possible infection sources, Cryptosporidium spp. and E. bieneusi in fecal specimens from 90 HIV‐infected patients attending antiretroviral clinics in Lagos, Nigeria were detected and genotyped by PCR and DNA sequencing. Cryptosporidium spp. and E. bieneusi were identified in four and five patients, respectively, including the occurrence of subtype IeA11T3G3 of Cryptosporidium hominis in two patients, subtype IIcA5G3k of Cryptosporidium parvum in one patient, and Type IV of E. bieneusi in four patients. Among the remaining positive patients, one had mixed infection of Cryptosporidium meleagridis and C. hominis and one had mixed E. bieneusi genotypes. These data highlight a possible difference in major transmission routes (anthroponotic vs. zoonotic) between Cryptosporidium spp. and E. bieneusi in HIV+ patients in the study area.
Attitudes Toward and Management of Fibromyalgia: A National Survey of Canadian Rheumatologists and Critical Appraisal of Guidelines

Background Canadian rheumatologists' attitudes toward and management of fibromyalgia remain uncertain. Objective The aim of this study was to explore management strategies and attitudes of Canadian rheumatologists toward fibromyalgia and concordance with guideline recommendations. Methods We administered a 17-item cross-sectional survey to Canadian rheumatologists and explored the concordance between respondents' management practices with the 2012 Canadian Guidelines for the diagnosis and management of fibromyalgia. Results Among 331 Canadian rheumatologists who were approached, 140 returned the survey for a 42% response rate. The majority felt that fibromyalgia was a useful clinical diagnosis (110/138 [80%]) but was divided as to whether fibromyalgia was objectively defined (75/138 [54%]) or a psychosocial condition (42/138 [30%]) or could result in an inability to work (37/138 [27%]). Contrary to guideline recommendations, most (82/134 [61%]) endorsed that tender points were useful for diagnosis. Half endorsed potentially refusing consultations with fibromyalgia patients, and only 42% (59/139) agreed that there were effective therapies for this syndrome. Consistent with the guideline, most respondents managed fibromyalgia with education, exercise therapy, antidepressants, and nonnarcotic analgesics (≥89% for all); however, fewer than half agreed that any of these modalities were effective (endorsement ranged from 9% to 47%). Assessment of the 2012 guideline revealed a number of important limitations. Conclusions Canadian rheumatologists largely do not provide primary care for fibromyalgia. Most adhere to guideline recommendations for management of fibromyalgia, but few endorse these interventions as effective. Further research, including updating of the 2012 Canadian Guidelines for the diagnosis and management of fibromyalgia, is required to inform this disconnect.
Environmental fate and chemistry of a veterinary antibiotic—tylosin

Aerobic degradation, photolysis, and mobility of tylosin were investigated in the laboratory. Tylosin A is degraded with a half-life of 200 d in water, while it is stable in the dark. Tylosin C and D are relatively stable except in ultrapure water in the light. Slight increases of tylosin B and formation of two photoreaction products, isotylosin A alcohol (E,Z) and isotylosin A aldol (E,Z), were observed under exposure to light. In soil tylosin A and D has a dissipation half-life of about 1 wk. Sorption and abiotic degradation are the major factors influencing the loss of tylosin in the environment. No biotic degradation was observed at the test concentration of 50 μg/ml or μg/g either in pond water or in an agronomic soil, as determined by comparing dissipation profiles in sterilized and unsterilized conditions. At 7.5 ng/ml, biotransformation may play an important role in degradation of tylosin in water. Tylosin has strong sorption to various soils, and leachbility is dependent on soil properties and manure amendment. Adsorbed tylosin in surface soil might run off to water bodies through soil erosion. In the end, pathways were proposed for tylosin degradation in the environment.
Expression and transient nuclear translocation of proprotein convertase 1 (PC1) during mouse preimplantation embryonic development

Preimplantation embryos express a number of hormones, neuropeptides, and membrane receptors known to derive from proteolytic activation of their precursors by the seven‐member family of subtilisin‐like, calcium‐dependent serine proteinases known as proprotein convertases (PCs). The goal of this study was to determine the pattern of PC expression in mouse preimplantation embryos. Transcripts for all PCs, except PC2, were detected by reverse transcription‐polymerase chain reaction (RT‐PCR) in unfertilized and fertilized eggs. Furin, PACE4, PC1, and PC7 transcripts remained present at subsequent stages of preimplantation embryonic development, whereas the levels of transcripts for PC4 and PC5 gradually disappeared after the 2‐cell stage. Proprotein convertase 1 (PC1) expression was further examined at the protein level. Immunoblotting revealed the presence of the zymogen and mature forms of this enzyme in eggs and embryos. Immunofluorescence laser confocal microscopy showed PC1‐specific staining throughout the cytoplasm of unfertilized eggs. After fertilization, surprisingly, the staining was concentrated in pronuclei. It relocated to the cytoplasm at postzygotic stages and was particularly strong at junctions between blastomeres. The nuclear translocation of PC1 in fertilized eggs is probably mediated by its prodomain. Indeed, when transduced in human colon carcinoma LoVo cells, a mutant proPC1 incapable of cleaving off its prodomain was shown to accumulate in the nucleus. Furthermore, when N‐terminally fused to green fluorescent protein, this domain was able to direct the reporter protein to the nucleus of these cells. Collectively, these data establish that eggs and preimplantation embryos express various PCs necessary for proteolytic activation of precursors of hormones and growth factors. They also raise the possibility of a nuclear function for PC1 during zygote formation. Mol. Reprod. Dev. © 2005 Wiley‐Liss, Inc.